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									         Brain 2
Jaskaran Singh, Katherine Barco*,
  Young Sun Song, Priscilla Vu

        Thursday 11 a.m.
                        *katebarco@yahoo.com
Neurons: The Basic Units of
         the Brain
        Jaskaran Singh
         Brain Group
                                    Outline
 Neuron Overview
 Myelin Sheath
 Action Potential
 Propagation of the Signal
 Neuron Membrane
 Neuron as an Electrical Circuit
Neuron Overview
Myelin
Action Potential Sequence
Propagation of the Signal
                                        Propagation Cont.

Unmyelinated    Diameter      Speed
  Neurons       (micro)m       m/s
  Human             10            0.5

   Crab             30            5

   Squid           500            20




   http://www.brainviews.com/ab
   Files/AniSalt.htm
            Neuron Membrane

       Node of Ranvier



axon




       Myelinated areas
Neuron Membrane Cont.
Neuron as an Electrical Circuit
                                                    Summary
 A neuron is more than just cell, it is an electrical circuit too.

 At the nodes, the Resistance is low.
    This results in the current (ions) to flow easier in and out of
      the cell.
    The more ion channels that are open the more resistors in
      parallel there are and therefore the lower the resistance is.

 Myelin plays an important part in making sure that the current
  propagates quickly and without loosing potential and produces an
  induced current.
                                      References
http://physicsbuzz.physicscentral.com/2007/08/making-neurons-
    remember.html

www.answers.com/ topic/action-potential

www.getrealscience.com/ 2007WilsonIBBiology/

http://en.wikipedia.org/wiki/Neuron

http://www.fortunecity.com/greenfield/buzzard/387/actionpot.htm

http://people.eku.edu/ritchisong/301notes2.htm

http://www.fortunecity.com/greenfield/buzzard/387/neuronsascircui
    t.htm
         Epilepsy
Using genetics and EEG to understand
          seizure disorders

                   Katherine Barco
                     Brain 2_T11
    Presentation Outline

   •Neuronal activity and action
           potentials

• Electroencephalography of seizures

     • Epileptiform discharges

  • Voltage-gated sodium channels

        • Genetic mutations
         Excitatory and inhibitory
             neuronal activity
Voltage-gated ion channels:
• Sodium and calcium channels facilitate depolarization of
cell membrane toward action potential (AP) threshold;
excitatory.

•Potassium channels function to
hyperpolarize cell membrane away
from AP threshold;
inhibitory.

Ligand-gated receptors:
• Mediate signals from
neurotransmitters (glutamate and
gamma-aminobutyric acid or GABA)
                Neuronal Circuits




• Gradient of sodium outside and potassium ions inside the cell
• Summation of individual EPSPs along a portion of the
postsynaptic membrane allows cell to reach threshold and fire an
action potential
    EEG Basics
•16-25 electrodes placed over
different brain regions

• EEG measures the
electrical potentials of
cortical neuronal dendrites

• Detects negative potential
of extracellular space

• Signals at the scalp are on
the order of 10-100
microvolts in amplitude
         Epileptiform Discharges




• Common between overt seizures (interictally) and
during seizures (ictally)
•Abnormalities include spikes (70 msec) and sharp
waves (70-200 msec)
• Represents synchronously occurring PDS in several
million neurons.
  Paroxysmal Depolarization Shift
• Intracellular correlate
of an interictal spike on
surface EEG

• Initial rapid and
prolonged depolarization
of the membrane
potential

• Followed by burst of
repetitive action
potentials lasting several
hundred milliseconds
                             Source: Khoshbin et al. Clinical Neurophysiology (2008)
     Structure of voltage-gated
         sodium channels




• Alpha subunits:               • Beta
   • Four homologous              subunits:
   domains                      • Two -sheets
   • Each domain contains six   linked by
   -helical segments           disulfide bridge
 SCN1A
mutations
• Inherited
  and de novo
  mutations
• Missense:
  single
  nucleotide
  substitution
• Truncation
  (nonsense,
  frameshift)
      SCN1A S4 voltage sensors




 positively charged amino acid residue, “gating charges”
• Change in membrane electric field  conformational
change to open pore  depolarization
                 Inactivation
• Channels inactivate within milliseconds of opening
• Isoleucine, phenylalanine, methionine motif critical
   • Serves as tethered inner pore blocker
• Mutations of residues impair inactivation
             SCN1B mutations




• C121W mutation—destabilizes extracellular fold
• Disrupts modulation of channel-gating kinetics
• Slower inactivation  persistent inward Na+ currents
 hyperexcitability
               Main Points
• Action potentials are stimulated by movement of
        ions across voltage-gated channels

 •PDS represents the intracellular equivalent of
      spike-slow wave complex on EEGs

• Inherited and de novo mutations present in genes
             of patients with epilepsy

   •Mutations in highly conserved regions alter
  sodium channel function, resulting in neuronal
                hyperexcitability
                                References
Catterall, W. A. (2000). From ionic currents to molecular mechanisms: the structure and
          function of voltage-gated sodium channels. Neuron, 26(1): 13-25.
Fisher et al. (2006). EEG for Beginners. Stanford Neurology Core Clerkship.
Hirsch et al. (2008). Electroencephalography (EEG) in the diagnosis of seizures and epilepsy.
                    UpToDate.
Kearney, J. A., & Meisler, M. H. (2005). Sodium channel mutations in epilepsy and other
          neurological disorders. Journal of Clinical Investigation, 115(8): 2010-2017.
Khoshbin et al. (2008). Clinical Neurophysiology. UpToDate.
Mulley, J. C. (2005). SCN1A mutations and epilepsy. Human Mutation, 25, 535-542.
Rho, J. M. et. al. (2004). Epilepy: Scientific Foundations of Clinical Practice. New York:
          Marcel Dekker, Inc.
Stafstrom et al. (2008). Pathophysiology of seizures and epilepsy. UpToDate.
Wallace, R. H. et. al. (1998). Febrile seizures and generalized epilepsy associated with a
         mutation in the Na+-channel B1 subunit gene SCN1B. Nature Genetics, 19, 386-
         370.
Wallace, R. H. et. al. (2001). Neuronal Sodium-channel a1-subunit mutations in generalized
         epilepsy with febrile seizures plus. Human Genetics 68, 859-865.
Yamakawa, K. (2006). Na channel gene mutations in epilepsy—the functional consequences.
         Epilepsy Research, 70, 218-222.
WebMD (http://www.webmd.com/epilepsy/electroencephalogram-eeg-21508?page=1)
http://www.richardschiropractic.com/blog1/uploaded_images/website_EEG-764486.jpg
http://3.bp.blogspot.com/_DZH2cmCoois/Re2TAYZm1sI/AAAAAAAABRg/DZVmr9Ar3eI/
          s200/ion_channel_Figure_9_30.jpg
Current Methods in Treating Alzheimer’s
              Disease

______________________________________
                   _



  By Priscilla Vu
  Brain 2 T11 Group

______________________________________
                   _
          Outline
• Introduction of Disease:
  Characteristics of Disease and
  Causes
• Potential Ways of Intervention
• Current Pharmaceuticals that
  Prevent/Delay Alzheimer’s
  (Acetylcholinesterase and
  Memantine)
Physical Manifestations of Alzheimer’s
     Plaques and Tangles:
Characteristic Traits of Alzheimer’s
  Amyloid Beta
    (Plaques)
and Tau (Tangles)
   Hypothesis
Causes of Alzheimer’s: Aggregation of Plaques
      0:26-1:14 Amyloid Beta Receptors
Causes of Alzheimer’s:
Affect on Neurotransmitter
         Synapse
      Potential Intervention:
Amyloid Beta Receptor Immunizations
Potential Intervention: Blocking Beta-Amyloid Receptors
                 0:34-1:38 Rage Receptors
Potential Intervention: Dissolving
        Tau Aggregations
Combined Effects of Tau and Beta-Amyloid
 Pharmaceuticals:
Acetylcholinesterase
Pharmaceuticals: Memantine
 (NMDA receptor antagonist)
The Big   •Tau, Beta-Amyloid, and Cholinergic Hypothesis
          •Pharmaceuticals: Acetylcholinerase and Memantine
Picture
                                                                Sources
Illustration of Alzheimer’s Image:
     http://upload.wikimedia.org/wikipedia/commons/thumb/9/91/COMPARISONSLICE_HIGH.JPG/800px-
     COMPARISONSLICE_HIGH.JPG
MRI image of Alzheimer’s:
     http://msnbcmedia3.msn.com/j/msnbc/Components/Photos/041102/041102_mayoclinic_bcol_11a.standa
     rd.jpg
Plaques and Tangles Image:
     http://www.realage.com/health_guides/Alzheimer/img%5CLivingWithAlzheimers_artv1.jpg
Tau Hypothesis Image:
     http://upload.wikimedia.org/wikipedia/commons/thumb/5/51/TANGLES_HIGH.jpg/800px-
     TANGLES_HIGH.jpg
Beta-Amyloid Hypothesis Image: http://upload.wikimedia.org/wikipedia/commons/thumb/f/fb/Amyloid-
     plaque_formation-big.jpg/800px-Amyloid-plaque_formation-big.jpg
Aggregation of Plaques Video:
     http://www.youtube.com/watch?v=zgYixMPFthQ
Synapse: http://www.nature.com/nrn/journal/v6/n9/images/nrn1754-i1.jpg
Nerve : http://library.thinkquest.org/4371/media/nerves.bmp
Beta-Amyloid Potential Interventions Image:
     http://stahlonline.cambridge.org/content/ep/images/85702c18_fig30.jpg
Rage Receptors Video: http://www.youtube.com/watch?v=zHx3dPMFRJM
Tau Potential Interventions Video: http://www.youtube.com/watch?v=pEz3D6LYTzs&feature=related
Combined Tau/Amyloid Image: http://www.nature.com/nrn/journal/v3/n11/images/nrn960-f3.jpg
Acetylcholinerase Image: http://www.cnsforum.com/content/pictures/imagebank/hirespng/Drug_neostig.png
Memantine Image: http://www.nature.com/nrn/journal/v8/n10/images/nrn2229-f4.jpg

								
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