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					Neuroscience Center
   Annual Report 2006

Preface                                                             4
Organization of the Neuroscience Center                             8
Research groups                                                     9
Adjunct professors                                                  10
Teaching at the Neuroscience Center                                 11
Core facilities
        Mouse behavioural unit                                      15
        Mouse transgenic unit                                       16
        Neuronal cell culture unit                                  17
        Zebrafish unit                                              18
Neuroscience Center research and centres of excellence
        Centre of excellence in complex disease genetics            19
        Finnish Centre of Excellence in Molecular and Integrative
        Neuroscience Research                                       19
Commercialization program                                           20
Administration                                                      21
Publications 2006                                                   22
Theses 2006                                                         25
Patents 2006                                                        25
Finances                                                            26
Staff                                                               27
4                                         ANNUAL REPORT 2006

    Preface                                           T    he University Senate founded the Neuroscience
                                                           Center (NC) for the five-year period 2002-2006,
                                                      after which its continuation and administrative position
                                                      were to be re-evaluated. The NC has operated as an
    Heikki Rauvala
                                                      independent research and teaching institute.
    Director of the Neuroscience Center
                                                        Since the NC was evaluated as a start-up institute in
                                                      2005 in the evaluation of University of Helsinki, the
                                                      Scientific Council of the University of Helsinki decided to
                                                      use this evaluation as the basis of its recommendations
                                                      to the University Senate in 2006. The Scientific Council
                                                      unanimously recommended continuation of the NC,
                                                      and the University Senate concluded in June 2006 to
                                                      further extend the NC for the five-year period 2007-
                                                      2011 as an independent research and teaching
                                                      institute. A precondition of this decision is that a plan
                                                      be presented by the end of 2008 detailing the
                                                      organization of the neuroscience research within the
                                                      structure of the University of Helsinki.

                                                      Areas of Current and Future Research at
                                                      the NC
                                                      During 2002-2006 the NC found its niche within the
                                                      biomedical community of the University of Helsinki.
                                                      Studies at the molecular/cellular level are a strength of
                                                      the Center and have a major impact on all of its
                                                      research areas, including development/plasticity, basic
                                                      mechanisms of nervous system diseases, and systems-
                                                      level studies, where mutant mouse technologies are
                                                      used to dissect mechanisms of behaviour.
                                                           In molecular/cellular research, several novel
                                                      possibilities exist that should be more effectively
                                                      exploited in forthcoming years. These include studies at
                                                      the structural biology level using X-ray crystallography
                                                      and nuclear magnetic resonance (NMR), fields that have
                                                      been greatly enhanced at the University of Helsinki
                                                      within the last few years. Another example is the
                                                      combination of molecular/cellular approaches with
                                                      modern imaging and electrophysiology in studies on
                                                      synaptic plasticity. Novel plasticity mechanisms are
                                                      currently being unravelled by researchers of the NC
                                                      using these methods.
                                                          Novel proteins and mechanisms regulating neuronal
                                                      development/plasticity or having neurotrophic functions
                                                   ANNUAL REPORT 2006                                                       5

have been discovered by the NC groups in recent years.        the Meilahti and Viikki campuses to shed light on how
Their functional roles have mainly been examined with         these mutations affect neuronal excitability and
neuron cultures and are currently being addressed             plasticity. Novel insights into the mechanisms of
using mouse transgenic technology. Since these types of       epilepsies are anticipated from these research lines.
molecules display neuroprotective actions, studies to              Febrile seizures are common in children and are
elucidate their roles in Alzheimer´s disease (in              characteristic of epileptic syndromes in which the
collaboration with the University of Kuopio) and              triggering mechanisms have been unclear. Very recent
Parkinson´s disease (in collaboration with the Faculty of     research has provided an explanation for the febrile
Pharmacy, University of Helsinki) are currently underway.     seizures by showing that hyperthermia causes
     A large portion of NC research is devoted to             respiratory alkalosis in the brain that is sufficient to
functional studies of genes regulating development and        induce seizures. The clinical implications of these
plasticity of the brain. Manipulation of such genes           findings are apparent, and studies on therapies of
using mouse transgenics is expected to reveal                 febrile seizures in humans are currently underway based
interesting behavioural phenotypes. This has already          on research of the basic mechanism.
been clearly documented for neurotrophic factors in                  Like the mouse transgenic/behavioural studies
emotional regulation, particularly depression. Molecular      cited above, projects using the zebrafish model are
regulation of endophenotypes of schizophrenia can be          characteristic of NC research and are unique in Finland.
investigated using mouse transgenic techniques                As pointed out in the evaluation of the departments of
combined with behavioural testing. In studies on              the University of Helsinki, the possibility to use both
human behavioural disorders, collaboration with the           vertebrate models in the NC to study brain
National Public Health Institute is expected to be fruitful   development/plasticity and behaviour is a novel
in forthcoming years.                                         situation in neuroscience research. The zebrafish system
     Furthermore, studies at the NC on mechanisms of          will be used to explore the roles of genes of interest in
normal and abnormal behaviour at the biosciences level        brain development, the imaging of which can be carried
are linked to human psychology and brain research (the        out at high accuracy, identifying specific neurons with
Faculty of Behavioral Sciences and the Helsinki University    defined transmitter phenotypes. It appears that the
of Technology). Collaboration between human                   zebrafish can also be used as a disease model, allowing
psychology researchers and human brain researchers            rapid screening of drug candidates. Use of the
has already been initiated and is reflected in                zebrafish model by the NC groups for studies of genes
neuroscience teaching. Informatics approaches focusing        of interest will increase during the next few years, and is
on computational methods have recently been initiated         expected to produce novel insights into development/
as part of NC research and teaching. This development         plasticity of the brain and neuronal disease
is expected to strengthen systems neuroscience at the         mechanisms.
NC and to foster research contacts with human
psychology.                                                   Teaching at the NC
       Genetic mechanisms of epilepsies form a focus in       The NC has taken an active role in creating systematic,
NC research of basic mechanisms of nervous system             high-level teaching in the field of neuroscience in
diseases. Several mutations underlying epilepsies have        Finland. Teaching has been organized according to
been defined during the last few years, and elucidating       molecular/cellular, developmental, cognitive/systems,
the mechanisms causing the disease is expected to be a        and disease-oriented neuroscience research, with both
major step on the path to finding novel treatment             lectures and hands-on laboratory courses.
strategies. Electrophysiological and imaging approaches            Teaching provided by the NC groups forms a major
are currently applied in collaborative studies between        part of the Master´s Program of Neuroscience that will

                be initiated in 2008. The Faculty of Biosciences acts as
                the major faculty partner in the program.
                     In addition to graduate-level teaching, the NC
                cooperates with the Finnish Graduate School for
                Neuroscience (FGSN), the Helsinki Graduate School of
                Biotechnology and Molecular Biology (GSBM), and the
                Helsinki Biomedical Graduate School (HBGS) to arrange
                special courses for PhD training.
                     Furthermore, via its representative in NENS (Network
                of European Neuroscience Schools), the NC participates
                in creating standards for European Master’s and
                Doctorate degrees in neuroscience.

                Societal Interactions of the NC
                Networking with other institutions is a characteristic
                feature in the operations of the NC. One important
                means for this cooperation is the adjunct professor
                system, which has created common research and
                teaching activities with the University of Kuopio, the
                Helsinki University of Technology, and other
                departments within the University of Helsinki. In human
                molecular genetics, the NC collaborates closely with
                Folkhälsan and the National Public Health Institute.
                     A commercialization program (NeuProtec) was
                launched in 2005 in collaboration with the Institute of
                Biotechnology and the Finnish Funding Agency for
                Technology and Innovation (TEKES). The aim of this
                program is to find novel tools for brain protection. A
                further aim is to create spin-off industrial activity based
                on neuroscience research during the next few years.
                     The NC was actively engaged in arranging the Brain
                Awareness Week in 2006, an activity now planned to
                take place yearly to enhance public understanding of
                neuroscience research. In this context, the initiative of
                the Brain Foundation of Finland (Suomen Aivosäätiö)
                was launched in 2006.

                Towards the Second Five-Year Period
                After my five-year term as Director, I feel that the NC can
                now be regarded as an established institution. I expect
                that during the second five-year period, which is now
                starting, the NC will have an even stronger impact in
                research. Teaching that corresponds to a Master´s
                                                  ANNUAL REPORT 2006   7

Program in Neuroscience has now been implemented
for three years and will be formally established in 2008.
Together with PhD training courses, the Master´s
courses will be an important activity of the NC.
     Functions of the NC would not have been possible
without the competitive funding that currently
comprises about 60 % of the budget of the NC. In
particular, the Sigrid Jusélius Professorhip in
Neuroscience has been invaluable to the NC. A large
proportion of our budget has been covered by
numerous grants from the Sigrid Jusélius Foundation,
the Academy of Finland, and the Finnish Funding
Agency for Technology and Innovation (TEKES).
     In conclusion, I would like to thank everyone at the
NC, our collaborators, and the members of the Boards
for making the Center an inspiring place to work. I am
very much looking forward to an even brighter five-year
8                                           ANNUAL REPORT 2006

                              Organization of
                          the Neuroscience Center

      Scientific Advisory Board                       Board


                                                                                           Core Facilities

                                                                                  • Mouse Transgenic Unit
                                                                                  • Mouse Behavioural Unit
                                                                                  • Neuronal Cell Culture Unit
                                                                                  • Zebrafish Unit

       Research and Teaching                        Network                              Commercialization
               Areas                                Activities                              Program

    • Molecular and Cellular Neuroscience   • Adjunct Professors
    • Developmental Neuroscience            • Faculty Departments
    • Cognitive and Systems Neuroscience    • Folkhälsan
    • Basic Research of the Nervous         • Helsinki University of Technology
     Systems Diseases                       • Institute of Biotechnology
                                            • National Public Health Institute
                                                ANNUAL REPORT 2006                                                       9

Research Groups

T   he mission of the Neuroscience Center is to carry out excellent and multidisciplinary research on the development,
    normal functions and disorders of the nervous system. Research and teaching in the NC focus on the following four
areas: molecular and cellular neuroscience, developmental neuroscience, cognitive and systems neuroscience, and basic
research of the nervous system diseases. The research groups work in at least one of the research areas of the NC. In
2006, there were seven research groups working in the NC.

     GDNF Family Receptors, KCC2, and Novel LRR Proteins in Nervous System Development and
     Matti Airaksinen

     Sigrid Jusélius laboratory
     Physiological, Pathophysiological, and Pharmacological Roles of Neurotrophins in the Adult Brain
     Eero Castrén

     Functional and Morphological Plasticity of Tripartite Synapse
     Leonard Khirug

     Mechanisms of Brain Disease: from Gene Mutation to Molecular Pathogenesis in Inherited Disorders
     Anna-Elina Lehesjoki

     Modulatory Neurotransmitter Systems and Their Role in Brain Diseases
     Pertti Panula

     Cell Surface and Extracellular Matrix Molecules in the Development and Plasticity of
     Neuronal Connections
     Heikki Rauvala

     Activity-Dependent Development and Plasticity in the Hippocampus
     Tomi Taira

                 Adjunct Professors

                  T   he Neuroscience Center may also have joint research
                       programs and activities with other parts of the
                  University of Helsinki, with other universities, research
                  centers or related units. The Neuroscience Center has
                  collaboration with four Adjunct professors to expand
                  and deepen the research and teaching areas. The
                  Adjunct professors were selected for a three-year period
                  starting in 2004.

                 Structural Biology of Targets Relevant to
                 Adrian Goldman
                 Institute of Biotechnology
                 University of Helsinki

                 From Sensory Processing to the Neural
                 Basis of Social Cognition —
                 Temporospatial Characterization of
                 Human Brain Function
                 Riitta Hari
                 Brain Research Unit
                 Helsinki University of Technology

                 Mechanisms of Electrical, Ionic, and
                 Trophic Signaling in the Brain
                 Kai Kaila
                 Department of Biological and Environmental Sciences
                 University of Helsinki

                 Hippocampal Dysfunction in Age-related
                 Memory Impairment
                 Heikki Tanila
                 Department of Neurobiology
                 A. I. Virtanen Institute
                 University of Kuopio
                                                     ANNUAL REPORT 2006                                                   11

Teaching at the                                                 gives an excellent opportunity
                                                                to design a neuroscience-

Neuroscience                                                    oriented master’s degree
                                                                regardless of whether the

Center                                                          major is, for example,
                                                                biochemistry, physiology, or
Eero Castrén                                                        In 2008, a new master’s
Phone +358 9 191 57626                                          program in neuroscience will                                        be launched. The NC will have
                                                                a central role in organizing
Tomi Taira                                                      the teaching curriculum as
Phone +358 9 191 59855
                                                                well as in carrying out the
                                                                teaching in the form of
                                                                specialized lectures and
                                                                laboratory courses.
                                                                    The NC is also responsible
                                                                for the organization of a

S    trong investment in research-based teaching is one
     of the central strategies of the University of Helsinki.
The position of the NC as an interdisciplinary research
                                                                master´s degree course in
                                                                neuroscience within the
                                                                Helsinki Biotechnology
institute gives it a unique opportunity to promote this         Course (HEBIOT). The first
task.                                                           students entered this program
    Neuroscience courses have already been organized            in August 2004. It is our
for several years at the graduate level at both the Viikki      intention that, in addition to
and Meilahti campuses. The NC currently organizes               students in the HEBIOT
several neuroscience graduate courses consisting of             program, other students with
both lecture courses and hands-on laboratory modules.           a suitable bachelor’s degree
In addition, every research group organizes a weekly            be able to participate in these
internal seminar series, which gives graduate students          courses. In the future, these
an opportunity to present their data and discuss their          courses, together with
projects with supervisors and group members. In 2006,           neuroscience courses given by the Faculties of
eight doctoral and five master´s theses were completed          Bioscience, Pharmacy, and Medicine on the Viikki and
at the NC. Currently, 40 doctoral theses and 11 master´s        Meilahti campuses, will form the foundation for a
theses are under preparation.                                   master´s program in neuroscience.
    All courses organized by the NC are in English. The             The NC training courses in neuroscience are
NC provides a wide range of neuroscience teaching that          currently undergoing considerable reorganization and
integrates recent research with undergraduate and               systematization. Training courses for graduate students
graduate courses. Lectures, seminars, and laboratory            are being organized in collaboration with the Helsinki
courses are designed in collaboration with experts in           Graduate School in Biotechnology and Molecular
teaching techniques to ensure high efficacy and quality         Biology and the Finnish Graduate School of
of teaching. Currently, teaching provided by the NC             Neuroscience, but instead of the “ad hoc” organization
equals the credits required to complete a major in a            applied thus far, our aim is to provide each course
master´s degree program. Thus, our teaching package             regularly, every two to three years.

                 COURSES ORGANIZED IN 2006

                 920001 Molecular neuroscience
                 (3 ECTS; lectures and exam)
                 Responsible person: Heikki Rauvala
                 Statistics: 16 passed the exam

                 920003 Functional neuroanatomy and
                 histology (3 ECTS; lectures and exam)
                 Responsible person: Matti Airaksinen
                 Statistics: 15 passed the exam

                 920007 Basic mechanisms of nervous
                 system disorders
                 (6 ECTS; lectures and exam)
                 Responsible persons: Anna-Elina Lehesjoki and Pentti
                 Statistics: 12/30 passed the exam

                 522277 Electrophysiological applications
                 in neurophysiology
                 (3 ECTS; practical course)
                 Responsible persons: Tomi Taira and Sari Lauri
                 Statistics: 15 applicants for the course in 2006, 6

                 522017 Synaptic signaling and plasticity
                 (4 ECTS; practical course, lectures, and
                 Responsible persons: Sari Lauri and Tomi Taira
                 Statistics: 10 applicants for the course in 2006, 6

                 920008 Optical imaging in neuroscience
                 (2 ECTS; practical course and exam)
                 Responsible person: Leonard Khirug
                 Statistics: 28 applicants for the course in 2006, 24
                                                 ANNUAL REPORT 2006                                                        13

Neuroscience Seminar Series 2006
Coordinator: Leonard Khirug
Phone +358 9 191 57644

T   he Neuroscience Seminar Series has been organized regularly since 2003 and has proven to be an important
    instrument of scientific exchange as well as student education. In 2006, over 20 seminars were held by international
and Finnish research scientists ranging from young independent researchers to celebrated Nobel laureate level. Speakers
are usually invited by the Neuroscience Center group leaders, and seminars cover a broad range of topics from
Neuroscience to Cell Biology. The audience of 30 to 50 people consists of graduate students, postdoctoral fellows and
senior faculty members. Guest speaker presentations are always followed by questions from the audience and vivid
discussions. For PhD students, regular attendance and active participation in the Neuroscience Seminars is counted as
points towards their study plan. In addition to the main presentation, each invited speaker is encouraged to spend time
with a number of group leaders individually, engaging in a more in-depth discussion of recent findings and mutually
interesting scientific questions.

 13.1.   Klaus Ballanyi (University of Alberta in Edmonton, Canada): A multiphoton microscopical look at the hot
         spot of breathing, the pre-Boetzinger Complex

 10.2.   Christian Hubner (Institute of Human Genetics, University Hospital Eppendorf, Hamburg, Germany):
         Physiological roles of K-Cl cotransporters revealed by knockout mouse models

 17.2.   Klaus Unsicker (Interdisciplinary Center for Neurosciences IZN, University of Heidelberg, Germany):
         The sympathoadrenal cell lineage of the neural crest: New perspectives for chromaffin cell development

 21.4.   Ralf Galuske (Department of Biology, Technical University Darmstadt, Germany):
         Cortical states and the polarity of orientation plasticity in primary visual cortex

 28.4.   Mark L. Andermann (Low Temperature Laboratory, Helsinki University of Technology): Novel tactile
         feature maps in rat somatosensory cortex

 11.5.   Per Svenningsson (Karolinska Institutet, Stockholm, Sweden): Modulation of 5-HT1B receptor function by
         p11 in depression-like states

 19.5.   Iiris Hovatta (National Public Health Institute, Biomedicum Helsinki): Gene expression profiling reveals a
         role for oxidative stress in the regulation of anxiety

 24.5.   Double special seminar:
         Masami Kojima (Research Institute for Cell Engineering RICE, National Institute of Advanced Science
         and Technology AIST, Osaka, Japan): Cell biology and genetically engineered animal of single nucleotide
         polymorphisms in BDNF gene. Looking into novel molecular mechanisms using genetic variation

         Nobuyuki Takei (Brain Research Institute, Niigata University, Japan): Translational control in neurons:
         Signaling mechanisms underlying local protein synthesis and its implications in plasticity and in disease
14                                              ANNUAL REPORT 2006

      9.6.    Andreas Jeromin (Center for Learning and Memory, University of Texas, USA):
              Molecular mechanisms of Kv4.2 trafficking in CA1 pyramidal neurons

     25.8.    Richard Paylor (Department of Molecular and Human Genetics, and Neuroscience, Baylor College of
              Medicine, Houston, USA): Anxiety, social interactions, and the role of genetic background in a mouse model
              of Fragile X syndrome

      1.9.    Anders Nykjaer (Department of Medical Biochemistry, Aarhus University, Denmark):
              The Vps 10p-domain receptor family: novel regulators of neuronal survival and death

     22.9.    Michael Courtney (Al Virtanen Institute, Kuopio): Signalling pathways mediating excitotoxic neuronal death

     29.9.    Carine Ali (INSERM, Cyceron, Caen, France): Tissue-type plasminogen activator as a positive modulator of
              NMDA-receptor dependent glutamatergic neurotransmission: physiopathological implications

     27.10.   Double special seminar:
              Klaus-Peter Lesch (Department of Psychiatry and Psychotherapy, University of Wuerzburg, Germany):
              Towards a molecular basis of attention deficit disorder (ADHD)

              Michael Meaney (Departments of Psychiatry and Neurology and Neurosurgery, McGill University,
              Montreal, Canada): Maternal care alters the postnatal development of defensive and reproductive strategies
              through effects on DNA methylation

     3.11.    Edgar Kramer (Department of Molecular Neurobiology, Max-Planck Institute of Neurobiology,
              Germany): RET in vivo function is motoneurons and dopaminergic system

     10.11.   Paul Kubes (University of Calgary, Faculty of Medicine, Institute of Infection, Immunity & Inflammation,
              Calgary, Canada): Leukocyte Recruitment into the Inflamed Brain Microvasculature

     20.11.   Alexey Semyanov (RIKEN Brain Science Institute, Japan and Nizhny Novgorod University, Russia).
              Extrasynaptic signaling in the brain mediated by diffuse glutamate

     24.11.   Marco Canossa (Department of Human and General Physiology, University of Bologna, Italy): Cortical
              neurons and astrocytes recycle BDNF for regulated secretion: implications for activity-dependent synaptic

     30.11.   Eleanor Coffey (Åbo Academy and University of Turku, Turku Centre for Biotechnology, BioCity):
              Opposite roles of JNKs in neuronal cell death and physiology

     8.12.    Double special seminar:
              Atsuo Fukuda (Department of Physiology, Hamamatsu University School of Medicine,
              Hamamatsu, Japan): Roles of NKCC1 and taurine in early neocortical development

              D. Carleton Gajdusek, Nobel Laureate in Medicine 1976 (NIH, US Dept. of HHS, Bethesda, USA)
              Spontaneous generation of infectious amyloid nucleants by conformational change in normal proteins
                                                 ANNUAL REPORT 2006                                                    15

Core Facilities                                           The analysis of mouse behaviour in laboratory
                                                          conditions is undergoing rapid evolution, and a
                                                          growing need exists for expertise in this field.
Mouse Behavioural Unit                                        The Mouse Behavioural Unit was started in 1998 to
                                                          provide research groups in neurobiology with the
                                                          possibility of characterizing their mutant mice. Since
Heikki Rauvala
                                                          then, the Unit has substantially expanded the repertoire
Phone +358 9 191 57621
                                                          of available tests and models. The systematic work for
                                                          improvement and refinement of the methods has been
                                                          recognized locally and internationally. We have
                                                          therefore been receiving an increasing number of
                                                          collaboration requests. The test battery for behavioural
                                                          phenotyping involves assessment of motor behaviour

M     ouse genetic models play a key role in the
      investigation of molecular pathways underlying
normal biological functions or pathological states. The
                                                          (coordination, spontaneous activity), nociception (hot
                                                          plate, tail withdrawal, plantar test, automated von Frey),
                                                          sensorimotor gating (prepulse inhibition of acoustic
models require extensive analysis at various levels of
                                                          startle reflex), emotional behaviour (elevated plus maze,
complexity. Behavioural testing is an important
                                                          light-dark exploration, open field, Y-maze, forced swim
approach in comprehensive studies aimed at
                                                          test), and learning and memory (spatial navigation in
understanding psychiatric and neurological diseases.
                                                          water maze, fear conditioning, conditioned taste
                                                          aversion, novel object recognition, social transmission
                                                          of food preference). Recently, the comprehensive
                                                          laboratory animal monitoring system was set up for
                                                          long-term (24-72 hours), automated, and noninvasive
                                                          collection of several physiological and behavioural
                                                          parameters (activity, food and water consumption,
                                                          metabolic performance) simultaneously.
                                                              In addition to the phenotyping of mutant mice,
                                                          basic research with commonly used inbred strains is
                                                          carried out to establish baseline values and to validate
                                                          models. These studies provide important background
                                                          information for interpretation of the data. More
                                                          specifically, we are interested in the interactions of
                                                          genetic background, sex, and environment in
                                                          modulation of behavioural patterns. Currently, we aim
                                                          at implementing stereotaxic surgery. This method allows
                                                          targeting of specific brain regions to detect lesions or
                                                          administer drugs. The Unit is awaiting new animal
                                                          facilities that will take into account the space
                                                          requirements and other specific needs of a mouse
                                                          behavioural laboratory.

                                                          Researchers Natalia Kulesskaya, PhD and Vootele Võikar,
                                                          MD, PhD
16                                       ANNUAL REPORT 2006

     Mouse Transgenic Unit
                                                     M       ouse transgenic technology has made it possible
                                                             to study molecular mechanisms of such complex
                                                     biological phenomena as development and behaviour.
                                                     In addition, disease models using mouse transgenics
     Heikki Rauvala
                                                     are becoming increasingly important.
     Phone +358 9 191 57621
                                                          The Transgenic Facility was launched in 1996, and its
                                                     first project was to produce overexpressing mice, a
                                                     project which has retained its usefulness. Production of
                                                     knockout mice using blastocyst injection was
                                                     established soon after classical transgenics. Morula
                                                     aggregation is currently mainly used for the production
                                                     of knockout mice.
                                                          The Transgenic Unit produces overexpressing and
                                                     knockout mice for the projects of several research
                                                     groups on the Viikki and Meilahti campuses, both
                                                     within and outside the Neuroscience Center. Altogether,
                                                     about 200 different mouse lines were produced during
                                                     1996-2005. Since Biomedicum on the Meilahti campus
                                                     now has its own transgenic facility, the current activity of
                                                     the Viikki Unit is mainly directed at meeting the needs
                                                     of the research groups on the Viikki campus; the
                                                     Institute of Biotechnology and the Neuroscience Center
                                                     are the main users of mouse transgenics.
                                                          An increasingly evident problem in mouse
                                                     transgenics is contamination of imported mouse lines,
                                                     which prevents housing in the animal facility and
                                                     increases the risk of facility contamination. Therefore,
                                                     purification of mouse lines using embryo transfer has
                                                     been established. In addition, freezing of mouse
                                                     embryos is carried out to ensure back-ups and for long-
                                                     term storage of mouse lines that are no longer under
                                                     active investigation.
                                                          By far, the major limiting factor in mouse transgenics
                                                     is inadequate capacity in the animal facility, resulting in
                                                     the expertise of the Unit not being fully exploited. The
                                                     use of spatially and temporally regulated transgenics, in
                                                     particular, requires large mouse colonies, and therefore,
                                                     sufficient housing facilities. State-of-the art testing in
                                                     behavioural studies also requires large numbers of
                                                     animals. Building a new animal facility is necessary
                                                     before increasing the number of studies using
                                                     transgenic mice.

                                                     Graduate student Anni Hienola, MSc
                                                     Technicians Kylli Haller and Raija Ikonen
                                               ANNUAL REPORT 2006                                                   17

Neuronal Cell Culture Unit                                  Furthermore, a core facility saves in expenses by
                                                        optimizing the use of cells and centralizing the purchase
                                                        of culture media, serum samples, and plasticware. In
Eero Castrén                                            addition to the cultures routinely prepared, the unit can
Phone +358 9 191 57626                                  provide cerebellar granule neurons, peripheral ganglia                                neurons, and hippocampal slice cultures. The unit has
                                                        facilities for transfection and viral transducion of gene
                                                        constructs to primary neurons and slice cultures. The
                                                        unit also provides cells and trained investigators to

T   he Neuronal Cell Culture Unit provides the groups
    in the Neuroscience Center and other research
groups in the Helsinki region with cultured neurons
                                                        other laboratories and campuses, including the

prepared from the embryonic rat and mouse               Personnel:
hippocampus and cortex. Centralization of the primary   Technicians Seija Lågas and Outi Nikkilä
neuronal culture activity is important in providing
continuity and improving quality and consistency of
these cultures.
18                                               ANNUAL REPORT 2006

     Zebrafish Unit                                          oligonucleotides, selection of new mutants from
                                                             mutation screens, and studies on mutants produced
                                                             with targeted lesions in genomes (TILLING).
     Pertti Panula                                               One of the goals is to extend efficient phenotype
     Phone +358 9 191 25263                                  analysis to a phase in which the CNS produces complex                               behaviours. Current projects aim at elucidating the roles
                                                             of newly identified genes, the mutations of which
                                                             produce severe human diseases. Models of human
                                                             diseases related to disorders of the aminergic neuronal

     F   ast embryonic development, transparent
         embryos, and the availability of a large number
     of mutants have rendered zebrafish one of the
                                                             systems are also being developed. The methods used
                                                             include gene cloning and expression analysis,
                                                             translation inhibition, developmental analysis using
     favorite models in developmental biology. Rapidly       microscopy and gene arrays, high-resolution imaging,
     increasing knowledge of the zebrafish genome has        and automated behavioural techniques. The recent
     also enabled efficient identification of important      addition of an aquarium space has enabled genetic
     genes in this species.                                  studies and maintenance of mutant fish strains to be
         Most studies on zebrafish thus far have             carried out.
     concentrated on identifying early developmental
     phenotypes from mutation screens. The research          Personnel:
     carried out at the Neuroscience Center focuses on       Post-doctoral fellows Juha Kolehmainen, MD, PhD;
     new methods utilizing high-resolution confocal          Maxim Moshnyakov, PhD and Piotr Podlasz, VMD, PhD
     and two-photon imaging of developing neuronal
                                                             Undergraduate students Ville Sallinen, BM; Maria
     networks, and automated quantitative behavioural
                                                             Sundvik, MSc; Anu Tiittula, BM and Veera Torkko, MSc
     analysis. These methods are combined with use of
     translation inhibition with morpholino                  Technicians Jenny Bergqvist, BSc and Henri Koivula, BSc
                                                  ANNUAL REPORT 2006                                                       19

Neuroscience                                                 funding in the Academy of Finland’s Centre of
                                                             Excellence programme period 2006-2011.

Center Research                                              Directors of the research teams:

and Centres of                                               Docent Anu Jalanko (National Public Health Institute)
                                                             Professor Juha Kere (UH and Karolinska Institutet)

Excellence                                                   Professor Jaakko Kaprio (UH)
                                                             Professor Kimmo Kontula (UH)
                                                             Professor Anna-Elina Lehesjoki (UH and Folkhälsan
                                                             Institute of Genetics)
                                                             Professors Aarno Palotie and Joe Terwilliger (UH)
                                                             Academy professor Leena Peltonen-Palotie (chairman;
                                                             National Public Health Institute and UH)

T    he national strategy for centres of excellence in
     research has been jointly developed with the
Academy of Finland and the National Technology               Finnish Centre of
Agency. The centre of excellence programme is one form
of research funding for promoting the development of
                                                             Excellence in Molecular and
creative research environments. All centres of excellence    Integrative Neuroscience
in research represent the cutting edge of their respective
fields. Candidates for centres of excellence include
research units or researcher training units, comprising      The Board of the Academy of Finland has selected 18
one or several high-quality research teams with shared       Centres of Excellence to the national CoE programme
and clearly defined research goals, which are at or have     for 2008-2013 at its meeting on 12 December 2006.
the potential of reaching the international forefront of     The newly selected CoE in Molecular and Integrative
their field.                                                 Neuroscience Research focuses on trophic factors in the
                                                             mechanisms of neuronal development, plasticity, and
                                                             disorders. The groups of the CoE have complementary
The Centre of Excellence in                                  expertise in the fields of molecular/cellular neuroscience,
Complex Disease Genetics                                     neurophysiology, neuropharmacology, and systems
                                                             neuroscience. The aim is to create a multidisciplinary
The group led by Professor Anna-Elina Lehesjoki is one
                                                             international FCoE in basic and translational
of the seven research groups forming the Centre of
Excellence in Complex Disease Genetics (CoECDG) of
the Academy of Finland. Research within the Center
                                                             Directors of the research teams:
aims at dissecting the genetic background of some
common diseases and their trait components by                Professor Mart Saarma (chairman; Institute of
combining special expertise with the sample resources        Biotechnology)
                                                             Academy researcher Urmas Arumäe (Institute of
accessible to the center investigators. The Center builds
on accomplishments of the Centre of Excellence in
                                                             Academy researcher Claudio Rivera (Institute of
Disease Genetics of the Academy of Finland (years
                                                             Biotechnology and Department of Biological and
2000-2005), but has a more extended research program         Environmental Sciences)
to reflect the development of the field as well as its own   Professor Kai Kaila (Department of Biological and
research progress: from Mendelian diseases to complex        Environmental Sciences and Neuroscience Center)
traits. The CoECDG combines diverse expertise of eight       Professor Heikki Rauvala (Neuroscience Center)
group leaders across three academic institutes in            Professor Eero Castrén (Neuroscience Center)
Finland and one in Sweden. The Center was chosen for         Docent Matti Airaksinen (Neuroscience Center)

                 Director: Saija Pihkanen
                 Phone +358 9 191 57625

                 T    he Commercialization program is co-funded by the
                      Finnish Funding Agency for Technology and
                 Innovation (TEKES) and the Neuroscience Center.
                 Commercialization is carried out by collaboration with
                 research groups. Various research projects are evaluated
                 on their commercial potential and industrial
                 applicability. The current project entity (NeuProtec)
                 includes four different projects: three of them aim to
                 show a proof of concept on efficacy for therapeutic use
                 in neurodegenerative diseases, and the aim of the
                 fourth project is to provide proof of concept and
                 scalability of a technology platform for screening small
                 synthetic molecules for the treatment of neuro-
                 degenerative diseases.
                      NeuProtec is a novel way of including commercial
                 aspects in research projects. NeuProtec is funded by
                 TEKES. The parties in this current research collaboration
                 include professors Eero Castrén and Heikki Rauvala
                 from the Neuroscience Center and professor Mart
                 Saarma from the Institute of Biotechnology and their
                 research groups. The target of this joint activity with
                 science and commercialization is to increase the value
                 and applicability of research results for industrial
                      The four projects are based on long-term research
                 performed in the groups. The commercial management
                 and collaboration includes management of IPR
                 (patents), contractual matters and fund raising. Thus it
                 provides a frame for fulfilling basic commercial criteria.
                 This collaboration is expected to enhance
                 commercialization of the research results by providing
                 industrial criteria to applied science, to a level where it is
                 possible with academic resources.
                      This is a pioneer program for applying the new, third
                 legal assignment for universities.
                                                      ANNUAL REPORT 2006                                                    21

Administration                                                 Administration Director
                                                               The Administration Director is responsible for the NC’s
                                                               administration and finances. She also functions as the
                                                               NC’s Deputy Director, unless otherwise stated by the
                                                               Director with regard to a particular matter. The
                                                               Administrative Services Unit and Maintenance personnel
                                                               are subject to the authority of the Administration
                                                               Director. The Administration Director of the NC is Anna
A   dministration of the Neuroscience Center (NC) is
    determined by the Board and the Director. An
important administrative body of the NC is the Scientific
                                                               Mattila, MSc.

Advisory Board, which promotes the NC’s scientific             Scientific Advisory Board
                                                               The NC has a Scientific Advisory Board that consists of
                                                               international members. This Board promotes the NC’s
The Board
                                                               scientific activities, issues statements on the competence
In 2006, the Board members were as follows: the                of applicants for the post of Director and the posts or
Chairman was Professor, Dean Matti Tikkanen (Faculty           duties of Research Directors, evaluates the NC’s
of Medicine); the Vice-Chairman was Professor Kielo            scientific programs, formulates initiatives, and provides
Haahtela (Faculty of Biosciences); and members were            statements on new research programs.
Professor Markku Kaste (Faculty of Medicine), Professor            The Scientific Advisory Board comprises a minimum
Christina Krause (Faculty of Behavioural Sciences),            of five and a maximum of ten distinguished researchers
Professor Pekka Männistö (Faculty of Pharmacy), Docent         from Finland or abroad in the scientific fields
Jouni Sirviö (Orion Pharma), Professor Outi Vainio             represented by the NC. The Rector of the University of
(Faculty of Veterinary Medicine), Researcher Juha              Helsinki appoints the members of the Board for a five-
Knuuttila (Personnel representative), Student Tuuli Lahti      year term based on the proposal of the Board of
(student representative), Master of Science Tomi Maila         Trustees.
(student representative), and Master of Science Juha              Currently, the Scientific Advisory Board consists of
Salmi (student representative). The Board had four             the following members:
meetings during the year.
                                                               Chairman: Professor Ole Petter Ottersen (Faculty of
                                                               Medicine, University of Oslo, Norway)
                                                               Members: Professor Anders Björklund (Wallenberg
The Director manages and supervises the NC’s activities        Neuroscience Center, Lund University, Sweden)
and finances, participates in its scientific activities, and   Professor Ulrich Dirnagl (Charite Hospital, Humboldt
oversees the preparation of matters for discussion by          University, Germany)
the Board and the Scientific Advisory Board and the            Professor Barry J. Everitt (Dept. of Experimental
execution of decisions. The Director also appoints or          Psychology, University of Cambridge, UK)
engages those members of the NC whose                          Professor Hans-Christian Pape (Medical School, Otto-
appointments or engagements are not otherwise                  von-Guericke-University, Germany)
regulated or provided for and authorizes the NC’s              Professor Ralf F. Pettersson (Ludwig Institute for Cancer,
agreements unless they require the approval of the             Karolinska Institute, Sweden)
Rector of the University of Helsinki. The Director of the      Dr. Geneviève Rougon, Directeur (Institut de Biologie du
NC is Professor Heikki Rauvala.                                Développement de Marseille [IBDM], Marseille, France)
22                                                    ANNUAL REPORT 2006

     Publications 2006                                               Gardiner, M.R. (2006). Evaluation of CACNA1H in
                                                                     European patients with childhood absence epilepsy.
                                                                     Epilepsy Res. 69: 177-181.
                                                                          12. De Wit, J., Eggers, R., Evers, R., Castren, E., and
         1. Airaksinen, M.S., Holm, L., and Hätinen, T. (2006).      Verhaagen, J. (2006). Long-term adeno-associated viral
     Evolution and the GDNF family ligands and receptors.            vector-mediated expression of truncated TrkB in the
     Brain Behav. Evol. 68(3): 181-190.                              adult rat facial nucleus results in motor neuron
         2. Anichtchik, O., Sallinen, V., Peitsaro, N., and          degeneration. J. Neurosci. 26(5): 1516-1530.
     Panula, P. (2006). Distinct structure and activity of                13. Hienola, A., Tumova, S., Kulesskiy, E., and
     monoamine oxidase in the brain of zebrafish (Danio              Rauvala, H. (2006). N-syndecan deficiency impairs neural
     rerio). J. Comp. Neurol. 498: 593-610.                          migration in brain. J. Cell Biol. 174: 4.
         3. Anttonen, A.-K., and Lehesjoki, A.-E. (2006).                 14. Hiltunen, J., Hari, R., Jousmäki, V., Muller, K.,
     Marinesco-Sjögren Syndrome. GeneReviews at                      Sepponen, R., and Joensuu, R. (2006). Quantification of
     GeneTests: medical genetics information resource                mechanical vibration during diffusion tensor imaging at
     (database online). University of Washington, 11 pp.             3 T. Neuroimage 32(1): 93-103.
         4. Aula, N., and Aula, P. (2006). Prenatal diagnosis of          15. Hlushchuk, Y., and Hari, R. (2006). Transient
     free sialic acid storage disorders (SASD). Prenatal Diag.       suppression of ipsilateral primary somatosensory cortex
     26: 655-658.                                                    during tactile finger stimulation. J. Neurosci. 26(21):
         5. Bakker, R.A., Lozada, A.F., van Marie, A., Shenton,      5819-5824.
     F.C., Drutel, G., Karlstedt, K., Hoffmann, M., Lintunen,             16. Hämäläinen, R., Joensuu, T., Kallijärvi, J., and
     M., Yamamoto, Y., van Rijn, R.M., Chazot, P.L., Panula, P.,     Lehesjoki, A.-E. (2006). Characterisation of the mulibrey
     and Leurs, R. (2006). Discovery of naturally occurring          nanism-associated TRIM37 gene: transcription
     splice variants of the rat histamine H3 receptor that act       initiation, promoter region and alternative splicing.
     as dominant-negative isoforms. Mol. Pharmacol. 69(4):           Gene 366(1): 180-188.
     1194-1206.                                                           17. Hämäläinen, R., Mowat, D., Gabbett, M.T.,
         6. Blaesse, P., Guillemin, I., Schindler, J., Schweizer,    O’Brien, T.A., Kallijärvi, J., and Leheskoski, A.-E. (2006).
     M., Delpire, E., Khiroug, L., Friauf, E., and Nothwang,         Wilms’ tumor and novel TRIM37 mutations in an
     H.G. (2006). Oligomerization of KCC2 correlates with            Australian patient with mulibrey nanism. Clin. Genet.
     development of inhibitory neurotransmission. J.                 70: 473-479.
     Neurosci. 26(41): 10407-10419.                                       18. Hätinen, T., Holm, L., and Airaksinen, M.S. Loss
         7. Castrén, M. (2006). Differentiation of neuronal          of neurturin in frog-comparative genomics study of
     cells in Fragile X Syndrome. Cell Cycle 5(14): 1528-1530.       GDNF family ligand-receptor pairs. Mol. Cell. Neurosci.,
         8. Castrén, M. (2006). Kantasoluistako ratkaisu             Epub ahead of print 2006 Dec 4.
     neurologisten sairauksien hoitoon? Suomen                            19. Joensuu, T., Kuronen, M., Alakurtti, K.,
     Lääkärilehti 45:1.                                              Tegelberg, S., Hakala, P., Aalto, A., Huopaniemi, L., Aula,
         9. Castren, E., and Tanila, H. (2006). Neurotrophins        N., Michellucci, R., Eriksson, K., and Lehesjoki, A.-E.
     and dementia: keeping in touch. Neuron 51(1): 1-3.              Cystatin B: mutation detection, alternative splicing and
         10. Castrén, E., Voikar, V., and Rantamäki, T. Role of      expression in progressive myoclonus epilepsy of
     neurotrophic factors in depression. Curr. Opin.                 Unverricht-Lundborg type (EPM1) patients. Eur. J. Hum.
     Pharmacol., Epub ahead of print 2006 Oct 16.                    Genet., Epub ahead of print 2006 Sep 27.
         11. Chioza, B., Everett, K., Aschauer, H., Brouwer, O.,          20. Kallijärvi, J., Hämäläinen, R., Karlberg, N., Sainio,
     Callenbach, P., Covanis, A., Dulac, O., Durner, M., Eeg-        K., and Lehesjoki, A.-E. (2006). Tissue expression of the
     Olofsson, O., Feucht, M., Friis, M., Heils, A., Kjeldsen, M.,   mulibrey nanism-associated Trim37 protein in
     Larsson, K., Lehesjoki, A.-E., Nabbout, R., Olsson, I.,         embryonic and adult mouse tissues. Histochem. Cell
     Sander, T., Siren, A., Robinson, R., Rees, M., and              Biol. 126: 325-334.
                                                      ANNUAL REPORT 2006                                                           23

    21. Kukko-Lukjanov, T.-K., Soini, S., Taira, T.,             overexpressing heparin-binding growth-associated
Michelsen, K., Panula, P., and Holopainen, I. (2006).            molecule. Neuroscience 139: 505-511.
Histaminergic neurons protect the developing                          31. Pääkkönen, K., Tossavainen, H., Permi, P.,
hippocampus from kainic acid-induced neuronal                    Rakkolainen, H., Rauvala, H., Raulo, E., Kilpeläinen, I.,
damage in an organotypic coculture system. J. Neurosci.          and Guntert, P. (2006). Solution structures of the first
26: 1088-1097.                                                   and fourth TSR domains of F-spondin. Proteins 64(3):
    22. Kyttälä, A., Lahtinen, U., Braulke, T., and              665-672.
Hoffman, S. (2006). Functional biology of the neuronal                32. Rantamäki, T., Knuuttila, J., Hokkanen, M.-E., and
ceroid lipofuscinosis (NCL) proteins. Biochim. Biophys.          Castren, E. (2006). The effects of acute and long-term
Acta 1762: 920-933.                                              lithium treatments on trkB neurotrophin receptor
    23. Laurén, J., Hu, F., Chin, J., Liao, J., Airaksinen,      activation in the mouse hippocampus and anterior
M.S., and Strittmatter, S.M. Characterization of myelin          cingulate cortex. Neuropharmacology 50(4): 421-427.
ligand complexes with the neuronal NOGO-66 receptor                   33. Raulo, E., Tumova, S., Pavlov, I., Hienola, A., Lauri,
family. J. Biol. Chem., Epub ahead of print 2006 Dec 29.         S., Taira, T., and Rauvala, H. (2006). The two
    24. Lauri, S.E., Palmer, M., Segerstråle, M., Vesikansa,     thrombospondin type I repeat domains of HB-GAM
                                                                 display a cooperative function in N-syndecan binding
A., Taira, T., and Collingridge, G.L. Presynaptic
                                                                 and regulation of synaptic plasticity. Scientific World
mechanisms involved in the expression of STP and LTP at
                                                                 Journal 6: 406-409.
CA1 synapses in the hippocampus.
                                                                      34. Rouhiainen, A., Tumova, S., Valmu, L., Kalkkinen,
Neuropharmacology, Epub ahead of print 2006 Aug 17.
                                                                 N., and Rauvala, H. Analysis of proinflammatory activity
    25. Lauri, S.E., Vesikansa, A., Segerstråle, M.,
                                                                 of highly purified eukaryotic recombinant HMGB1
Collingridge, G.L., Isaac, J.T., and Taira, T. (2006).
                                                                 (Amphoterin). J. Leukoc. Biol., Epub ahead of print 2006
Functional maturation of CA1 synapses involves activity-
                                                                 Sep 15.
dependent loss of tonic kainite receptor-mediated
                                                                      35. Safiulina, V.F., Afzalov, R., Khiroug, L., Cherubini,
inhibition of glutamate release. Neuron 50(3): 415-429.
                                                                 E., and Giniatullin, R. (2006). Reactive oxygen species
    26. Lindfors, P.H., Lindahl, M., Rossi, J., Saarma, M.,
                                                                 mediate the potentiating effects of ATP on GABAergic
and Airaksinen, M.S. (2006). Ablation of persephin
                                                                 synaptic transmission in the immature Hippocampus. J.
receptor glial cell line-derived neurotrophic factor family
                                                                 Biol. Chem. 281(33): 23464-23470.
receptor α4 impairs thyroid calcitonin production in                  36. Sairanen, M., O’leary, O.F., Knuuttila, J.E., and
young mice. Endocrinology 147(5): 2237-2244.                     Castrén, E. Chronic antidepressant treatment selectively
    27. Lindfors, P.H., Voikar, V., Rossi, J., and Airaksinen,   increases expression of plasticity-related proteins in the
M.S. (2006). Deficient nonpeptidergic epidermis                  hippocampus and medical prefrontal cortex of the rat.
innervation and reduced inflammatory pain in glial cell          Neuroscience, Epub ahead of print 2006 Oct 12.
line-derived neurotrophic factor family receptor α2                   37. Schuchmann, S., Schmitz, D., Rivera, C.,
knock-out mice. J. Neurosci. 26: 1953-1960.                      Vanhatalo, S., Salmen, B., Mackie, K., Sipila, S.T., Voipio,
    28. Mahjneh, I., Anttonen, A.-K., Somer, M., Paetau,         J., and Kaila, K. (2006). Experimental febrile seizures are
A., Lehesjoki, A.-E., Somer, H., and Udd, B. (2006).             precipitated by a hyperthermia-induced respiratory
Myopathy is a prominent feature in Marinesco-Sjögren             alkalosis. Nat. Med. 12(7): 817-823.
syndrome: a muscle computed tomography study. J.                      38. Semenov, A., Goldsteins, G., and Castren, E.
Neurol. 253(3): 301-306.                                         (2006). Phosphoproteomic analysis of neurotrophin
    29. Nystedt, J., Brandt, A., Vilim, F., Ziff, E., and        receptor TrkB signaling pathways in mouse brain. Cell.
Panula, P. (2006). Identification of transcriptional             Mol. Neurobiol. 26(2): 163-175.
regulators of neuropeptide FF gene expression. Peptides               39. Siintola, E., Lehesjoki, A.-E., and Mole, S.E.
27: 1020-1035.                                                   (2006). Molecular genetics of the NCLs: status and
    30. Pavlov, I., Rauvala, H., and Taira, T. (2006).           perspectives. Biochim. Biophys. Acta 1762(10): 857-
Enhanced hippocampal gabaergic inhibition in mice                864.
24                                                    ANNUAL REPORT 2006

          40. Siintola, E., Partanen, S., Strömme, P., Haapanen,      (2006). The layered fold of the TSR domain of P.
     A., Haltia, M., Maehlen, J., Lehesjoki, A.-E., and Tyynelä,      falciparum TRAP contains a heparin binding site. Protein
     J. (2006). Cathepsin D deficiency underlies congenital           Sci. 15(7): 1760-1768.
     human neuronal ceroid-lipofuscinosis. Brain 129: 1438-               48. Uvarov, P., Ludwig, A., Markkanen, M., Rivera, C.,
     1445.                                                            and Airaksinen, M.S. (2006). Upregulation of the
          41. Siiskonen, H., Oikari, S., Korhonen, V.P., Pitkänen,    neuron-specific K+/Cl- cotransporter expression by
     A., Voikar, V., Kettunen, M., Hakumäki, J., Wahlfors, T.,        transcription factor early growth response 4. J. Neurosci.
     Pussinen, R., Penttonen, M., Kiehne, K., Kaasinen, S.K.,         26(52): 13463-13473.
     Alhonen, L., Janne, J., and Herzig, K.H. Diazepam                    49. Vanhatalo, S., and Kaila, K. (2006). Development
     binding inhibitor overexpression in mice causes                  of neonatal EEG activity: from phenomenology to
     hydrocephalus, decreases plasticity in excitatory                physiology. Semin. Fetal Neonatal. Med. 11(6): 471-478.
     synapses and impairs hippocampus-dependent                           50. von Ossowski, I., Oksanen, E., von Ossowski, L.,
     learning. Mol. Cell. Neurosci., Epub ahead of print 2006         Cai, C., Sundberg, M., Goldman, A., and Keinänen, K.
     Dec 3.                                                           (2006). Crystal structure of the second PDZ domain of
          42. Sipilä, S.T., Huttu, K., Voipio, J., and Kaila, K.      SAP97 in complex with a GluR-A C-terminal peptide.
     (2006). Intrinsic bursting of immature CA3 pyramidal             FEBS J. 273(22): 5219-5229.
     neurons and consequent giant depolarizing potentials                 51. Vullo, D., Ruusuvuori, E., Kaila, K., Scozzafava, A.,
     are driven by a persistent Na+ current and terminated by         and Supuran, C.T. (2006). Carbonic anhydrase
     a slow Ca2+ -activated K+ current. Eur. J. Neurosci.             inhibitors: inhibition of the cytosolic human isozyme VII
     23(9): 2330-2338.                                                with anions. Bioorg. Med. Chem. Lett. 16(12): 3139-
          43. Sipilä, S.T., Schuchmann, S., Voipio, J., Yamada, J.,   3143.
     and Kaila, K. (2006). The cation-chloride cotransporter              52. Änkö, M.-L., and Panula, P. (2006). Regulation of
     NKCC1 promotes sharp waves in the neonatal rat                   endogenous human NPFF2 receptor by neuropeptide FF
     hippocampus. J. Physiol. 573(Pt 3): 765-773.                     in SK-N-MC neuroblastoma cell line. J. Neurochem. 96:
          44. Takahashi, M., Kakita, A., Futamura, T.,                573-584.
     Watanabe, Y., Mizuno, M., Sakimura, K., Castren, E.,                 53. Änkö, M.-L., Östergård, M., Lintunen, M., and
     Nabeshima, T., Someya, T., and Nawa, H. (2006).                  Panula, P. (2006). Alternative splicing of human and
     Sustained brain-derived neurotrophic factor up-                  mouse NPFF2 receptor genes: Implications to receptor
     regulation and sensorimotor gating abnormality                   expression. FEBS Letters 580: 6955-6960.
     induced by postnatal exposure to phencyclidine:
     comparison with adult treatment. J. Neurochem. 99:
          45. Tervonen, T.A., Ajamian, F., de Wit, J., Verhaagen,
     J., Castren, E., and Castren, M. (2006). Overexpression
     of a truncated TrkB isoform increases the proliferation
     of neural progenitors. Eur. J. Neurosci. 24: 1277-1285.
          46. Tornberg, J., Segerstråle, M., Kulesskaya, N.,
     Voikar, V., Taira, T., and Airaksinen, M.S. KCC2-Deficient
     mice show reduced sensitivity to diazepam, but normal
     alcohol-induced motor impairment, gaboxadol-induced
     sedation, and neurosteroid-induced hypnosis.
     Neuropsychopharmacology, Epub ahead of print 2006
     Aug 16.
          47. Tossavainen, H., Pihlajamaa, T., Huttunen, T.,
     Raulo, E., Rauvala, H., Permi, P., and Kilpeläinen, I.
                                                 ANNUAL REPORT 2006                                                     25

Theses 2006                                                Patents 2006
Doctoral Theses                                                Airaksinen, M.S., Lindahl, M., Timmusk, T., Poteriaev,
                                                           D., Rossi, J., and Saarma, M. Compounds related to or
    Alakurtti, Kirsi. Molecular biology of progressive     derived from GFRa4 and their use. EP 1257581,
myoclonus epilepsy of Unverricht-Lundborg type             08.03.2006.
(EPM1).                                                        Rauvala, H., Kuja-Panula, J., Võikar, V., and
    Hämäläinen, Riikka. Characterization of the TRIM37     Kulesskaya, N. Use of AMIGO-based technology to
gene and mutations underlying mulibrey nanism.             develop new treatment strategies for schizophrenia and
    Kallijärvi, Jukka. Biochemical and cell biological     other neuropsychiatric diseases. Patent application,
studies of Trim37 defective in mulibrey nanism.            2006
    Lindfors, Päivi. GDNF family receptors in peripheral
target innervation and hormone production.
    Pavlov, Ivan. Heparin-binding growth-associated
molecule (HB-GAM) in activity-dependent neuronal
plasticity in hippocampus.
    Rantamäki, Tomi. Brain TrkB neurotrophin receptor
as a target for antidepressant treatments.
    Tornberg, Janne. Generation and Characterization of
the Cation-Chloride Cotransporter KCC2 Hypomorphic
    Võikar, Vootele. Evaluation of methods and
applications for behavioural profiling of transgenic

Master’s Theses
    Hokkanen, Marie-Estelle. Expressionen av
serotonintransportern under den postnatala
utvecklingen och efter antidepressant medicinering i
    Knuuttila, Juha Eljas A. Antipsykoottisen lääkkeen
pitkäaikaiset vaikutukset rotan etuaivokuorella
DNAsirumenetelmällä tutkittuna.
    Lähteenmäki, Meri. Neurturiinin merkitys
parasympaattisen hermoston solulukumäärän
säätämisessä kehityksessä.
    Markkanen, Marika. Role of Upstream Stimulating
Factors (USFs) in the Transcriptional. Regulation of the
Neuron-specific K+/Cl—Cotransporter (KCC2).
    Reinmaa, Eva. Gene expression studies on the CSTB -
/- mouse model for Unverricht-Lundborg disease.
University of Tarto, Estonia.
26                                                     ANNUAL REPORT 2006

     Funding of the Neuroscience Center in 2006                             In euros               Percentage

     1. Basic funding                                                       2 351 000                  44%
     University of Helsinki (own assets)                                    1 200 000                22.7%
     University of Helsinki and Ministry of Education                       1 151 000                21.8%
     2. Competitive funding                                                 2 934 253                  56%
     Academy of Finland                                                       697 930                13.2%
     TEKES                                                                    539 393                10.2%
     Sigrid Jusélius Foundation                                               515 000                 9.7%
     Folkhälsan                                                               334 980                 6.3%
     Other state organizations                                                329 200                 6.2%
     Graduate schools                                                         173 800                 3.3%
     Other science organizations                                              164 814                 3.1%
     Biocentrum Helsinki                                                       92 500                 1.8%
     European Union                                                            59 103                 1.1%
     Performance-based funding                                                 27 533                 0.5%
     Total                                                                  5 285 253                 100%

                                    1,1 %                            University Helsinki (ow n assets)
                                                                    University of of Helsinki (own assets)
                            1,8 %            0,5 %
                    3,1 %                                           University of of Helsinki and Ministry of Education
                                                                     University Helsinki and Ministry of Education
            3,3 %
                                                                     Academy Finland
                                                                    Academy of of Finland
            6,2 %
                                                                    National Technology A gent
        6,3 %                                22,7 %                 Sigrid Jusélius Foundation
                                                                      Sigrid Jusélius Foundation


                                                                    Other state organizations
                                                                      Other state organizations
                                              21,8 %
                                                                    Graduate Schools
                                                                      Graduate Schools
        9,7 %       10,2 %          13,2 %
                                                                    Other science organizations
                                                                      Other science organizations

                                                                    Biocentrum Helsinki
                                                                      Biocentrum Helsinki

                                                                    European Union
                                                                      European Union

                                                                    Performance-based f unding
                                                                      Performance-based funding
                                                 ANNUAL REPORT 2006                               27

Personnel in 2006

                                        Number             %              PY*              %
 Researchers                             81              71.7             69.0            69.6
 Undergraduate students                  10               8.8              9.3             9.4
 Laboratory technicians                  15              13.3             15.0            15.1
 Administration                           5               4.4              4.8             4.8
 Maintenance                              1               0.9              1.0             1.0
 Computing                                1               0.9              1.0             1.0
 Total                                  113              100               99             100
 * person-years

Proportion   of foreign researches                                                     33.3%
Proportion   of PhDs in the category Researchers                                       53.1%
Proportion   of women in the categories Researchers and Undergraduate students         52.7%
Proportion   of women of all staff                                                     59.3%

                                1,0 %

                        4,8 %           1,0 %

               15,1 %
                                                                        Undergraduate students
                                                                         Undergraduate students
                                                                        Laboratory technicians
                                                                         Laboratory technicians
             9,4 %

                                                     69,6 %
28                                         ANNUAL REPORT 2006

     Group leaders                      Polvi, Anne, PhD**              Rantamäki, Tomi, MSc (Pharm) (PhD
                                        Pryazhnikov, Evgeny, PhD        defence 28.10.2006)
     Airaksinen, Matti, MD, PhD
                                        Rantamäki, Tomi, PhD            Rouhiainen, Ari, MSc
     Castrén, Eero, MD, PhD
                                        Raulo, Erkki, PhD               Sairanen, Mikko, MSc
     Khirug, Leonard, PhD
                                        Rossi, Jari, PhD                Sallert, Marko, MSc
     Lehesjoki, Anna-Elina, MD, PhD
     Panula, Pertti MD, PhD           Meilahti Campus
                                        Shmelev, Anton, PhD
                                        Sun, Xiaohong, PhD **
                                                                        Segerstråle, Mikael, MSc
                                                                        Siintola, Eija, MSc
     Rauvala, Heikki, MD, PhD
     Taira, Tomi, PhD                   Surin, Alexander, PhD **        Sundvik, Maria, MSc
                                        Tumova, Sarka, PhD              Tegelberg, Saara, MSc
     Adjunct professors                 Võikar, Vootele, PhD            Tervonen, Topi, MSc
                                        Wu, Xuefei, PhD                 Torkko, Veera, MSc
     Goldman, Adrian, PhD               Yamamoto, Yumiko, PhD **        Tornberg, Janne, MSc (PhD defense
     Hari, Riitta, MD, PhD                                              9.12.2006)
     Kaila, Kai, PhD                    Graduate students               Uvarov, Pavel, MSc
     Tanila, Heikki, MD, PhD                                            Vanttola, Päivi, MSc
                                        Alakurtti, Kirsi, MSc (PhD defense
                                                                        Vesikansa, Aino, MSc
     Senior scientists                  8.12.2006)
                                                                        Võikar, Vootele, MD (PhD defence
                                        Anttonen, Anna-Kaisa, MD
     Castrén, Maija, MD, PhD **                                         26.8.2006)
                                        Gransalke, Kathleen, MSc
     Lauri, Sari, PhD                                                   Zhao, Xiang, MSc ** (started as a
                                        Gyarfas, Tobias **
                                                                        graduate student 1.7.2006)
                                        Hienola, Anni, MSc **
     Post-doctoral fellows                                              Östergård, Maria, MSc
                                        Hokkanen, Marie-Estelle, MSc
     Afzalov, Ramil, PhD                Huupponen, Johanna, MSc
                                                                             Undergraduate students
     Aula-Kahanpää, Nina, PhD**         Hämäläinen, Riikka, MSc (PhD
     Di Lieto, Antonio, PhD **          defense 27.10.2006)                  Heinonen, Mirja **
     Jin, Cong-Yu, PhD                  Kallijärvi, Jukka, MSc (PhD defense  Kousi, Maria
     Joensuu, Tarja, PhD                5.1.2006) **                         Luisa Hasan Austin**
     Karlstedt, Kaj, PhD                Kiiltomäki, Marjaana, MSc            Lähteenmäki, Meri **
     Karpova, Nina, PhD **              Kirilkin, Ilya, MD                   Mankki, Lauri
     Kolehmainen, Juha, PhD             Knuuttila, Juha, MSc (Pharm)         Markkanen, Marika
     Kolikova, Julia, PhD               Kolehmainen, Juuso, MSc              Reinmaa, Eva
     Kopra, Outi, PhD (50% of time)     Kotilainen, Terhi, MSc               Saarenmaa, Tuomas
     Kulesskaya, Natalia, PhD           Kuja-Panula, Juha, MSc               Sallinen, Ville, BM
     Lahtinen, Ulla, PhD                Kulesskiy, Evgeny, MSc               Sundelin, Lotta **
     Lehtinen, Maria, PhD               Kupari, Jussi, MSc **                Tiittula, Anu, BM
     Lintunen, Minnamaija, PhD** Xiang **
                                        Kuronen, Mervi, MSc                  Zhao,
     Lyubimov, Yaroslav, PhD            Laakso, Tiina, MSc **
     Michelsen, Kimmo, PhD              Laurén, Juha, MD                     Visiting students
     Molchanova, Svetlana, PhD**        Lindfors, Päivi, MSc (PhD defense
                                                                             Giniatullina, Asiya
     Moshnyakov, Maxim, PhD**           1.9.2006) **                         Hofner, Peter
     Motin, Vladimir, PhD **            Lindholm, Jesse, MSc **              Kratochwil, Claudius
     Myllykangas, Liisa, MD, PhD        Markkanen, Marika, MSc (started as a Mäemets, Kristina
     O’Leary, Olivia, PhD               graduate student 7.9.2006)           Vashchinkina, Elena
     Podlasz, Piotr, VMD, PhD**         Priyadarshini Madhusmita**           Zebryk, Pawel
                                  ANNUAL REPORT 2006    29

Visiting post-doctoral   Administrative services unit
fellow                   and maintenance
Milosevic, Ira           Duus, Markus
                         Mattila, Anna, MSc
                         Maunula, Minna, MSc**
Visiting professor
                         Parviainen, Tarja
Hiroshi, Ohtsu**         Pihkanen, Saija, MSc
                         Tapani, Katri, BBA**
Technicians and other
technical staff          Computing
Berg, Kaija              Veteli, Petri
Bergqvist, Jenny
Hakala, Paula
Haller, Kylli
Harju, Anna              ** working part of the year
Hasenson, Paula
Huttu, Erja
Ikonen, Raija
Koivula, Henri
Lågas, Seija
Nikkilä, Outi
Olanne, Hanna
Saarikalle, Eeva-Liisa
Toivonen, Teija-Tuulia
Träskelin, Ann-Liz
Neuroscience Center Annual Report 2006

Editor                 Anna Mattila and Minna Maunula
Layout                 Anita Tienhaara
Photos                 Veikko Somerpuro and Eero Roine

Neuroscience Center
P.O. Box 56, Viikinkaari 4
FIN-00014 University of Helsinki, Finland
Phone +358 9 1911
Fax +358 9 191 57620
Yliopistopaino 2007