Potentials_Lectures_10_12

							Resting Potentials and Action
         Potentials

           Lecture 10
           PSY391S
         John Yeomans
 Special Properties of Neurons
• Excitability--Action Potential in Axons.
• Conduction--Action Potential in Axons.
• Transmission--Synapses, Electrical &
  Chemical.
• Integration--Postsynaptic Cell.
• Plasticity--Presynaptic Terminal and
  Postsynaptic Membrane.
Resting and Action Potentials
      Pumps Exchange Ions
• All cells have pumps and resting potentials
  (-40 to -90 mV).
• Pumps use ATP to exchange ions.
• Na+/K+ pump: 3 Na+ exchanged for 2 K+.
• Ca++ pump: Keeps powerful Ca++ ions
  out.
     Concentration of Ions and
     State of Channels at Rest




                                     -65 mV




Concentrations maintained by Na+/K+ and Ca++ pumps.
                 Potentials
• All potentials result from ions moving across
  membranes.
• Two forces on ions: Diffusion (from high to low
  concentration); Electrical (toward opposite
  charge and away from like charge).
• Each ion that can flow through channels reaches
  equilibrium between two forces.
• Equilibrium potential for each ion determined by
  Nernst Equation.
• K+ make - potentials; Na+ make + potentials.
             Nernst Equation
• EK+ = +58 mV log10 ([K+] outside/[K+] inside).

(+58 mV for room temperature, squid axon).

•   EK+ = 58 mV log10 1/20 = -75 mV.
•   ENa+ = 58 mV log10 10/1 = + 58 mV.
•   ECl- = -58 mV log10 15 = -68 mV.
•   ECa++ = +58 mV log10 10,000 = +220 mV.
   Resting Potential Results from
   Passive K+ Channels and EK+
• At rest, membrane potential is -60 to -70
  mV in most neurons. Why?
• K+ is most permeable, due to leak of K+
  through passive K+ channels.
• Therefore, K+ ions leave, making the
  inside more negative.
   Action Potential Results from
   Voltage-gated Na+ Channels
ENa+ = +58 mV     




EK+ = -75 mv 




        Closed!
           Action Potentials
• Only neurons and muscles have action
  potentials (not all neurons).
• Due to voltage-gated Na+ channels.
• Most in axons, at initial segment (axon
  hillock) and nodes of Ranvier. A few in big
  dendrites where depolarizations need a
  boost.
• Channel ionic currents are studied by
  voltage clamps and patch clamps.
             Voltage Clamp
• Used to measure ion currents in squid giant
  axons (Hodgkin & Huxley).
• Study single ion by changing ions in axon.
• Hold voltage constant by injecting current with
  large electrode. Measured current I.
• Measured Na+ or K+ current during action
  potential: INa+ = V/R = K/R ~ Na+ conductance.
• Measure “channel” permeability changes.
• Predicted action potential changes from Nernst
  Eq and channel permeabilities.
Single Channels

   Study electrical properties,
   Ionic properties,
   Pharmacology (toxins, agonists, antagonists)
   Molecular biology (mutant channels)
Voltage-gated Na++
Channel: Molecular
Structure and Gating
   (>1 m/s in mammals)




All Na+ channels open in APabsolute refractory period.

(No voltage-gated K+ channels in mammalian unmyelinated axons)
(1-120 m/s)
Synapses and Postsynaptic
       Potentials

         Lecture 11
         PSY391S
       John Yeomans
          Release and Ca++
• Transmitter is synthesized and stored in
  vesicles.
• Action potential opens voltage-gated Ca++
  channels near release sites.
• Ca++ activates proteins that move vesicles to
  release sites.
• Exocytosisrelease and diffusion of transmitter.
• EPSPs, IPSPs (depending on ions) .
• Reuptake or enzyme breakdown of transmitter.
   Chemical Receptors




Nicotinic, AMPA Na+   Muscarinic, Dopamine, GABAB
GABAA Cl-             Gs, Gi
Ionotropic Receptors
Receptors are now defined by genes
         Second Messengers
•   cAMP and cGMP, IP3, DAG (G-coupled)
•   Ca++, etc.
•   Kinases (dozens, e.g. A, CaMK)
•   Gene transcription (CREB)
•   Plasticity
•   Retrograde messengers NO and CO.
      Other Receptor Types
• Steroid receptors--Lipophilic molecules
  pass through membrane to act in neurons.
• Tyrosine kinase receptors--NGF activates
  enzymes and kinases.
• Slower growth effects.
Summation
                  PSPs
• Excitatory: Na+ or Ca++ entry.
• Inhibitory: K+ efflux or Cl- entry.
• Also blocking open channels (e.g. rods
  and cones).
• Slow potentials: seconds to hours.
Integration of Potentials

        Lecture 12
      John Yeomans
        PSY391S
Computation in Single Neurons
• Thinking requires complex computation.
  How?
• Neural computation occurs in postsynaptic
  cells, by integration of PSPs, and by
  changes in synapses.
• We still have no idea how thoughts are
  represented in neurons or circuits, only
  rough ideas of which brain regions are
  important.
Integration in the Cell and Axon




               PSPs decay with distance.

               Integration occurs at axon hillock.
Synapses on Soma, Dendrites and
            Spines




Thousands of synapses, of many types, on each output neuron.
          Synapse Strength
• Strongest near axon, usually inhibitory.
• Next strongest on soma and proximal
  dendrite shafts.
• Weakest synapses on spines, usually
  excitatory.
• Larger neurons usually have more
  synapses, more spines. Why?
                 Spines
• Problem: Too many synapsestoo much
  ion leakage along dendrites.
• Solution: Place synapses on isolated
  spines.
• All spine synapse have equal access to
  dendrite shafts.
• Spine shapes change in minutes:
  mushrooms less, slivers moreplasticity.
               Plasticity
• Facilitation and depression of PSPs.
• Presynaptic changes: transmitters,
  vesicles, release, retrograde NO.
• Postsynaptic changes: Receptors can be
  added and subtracted. Channels can be
  phosphorylated;
• Second messengers and kinases can
  change postsynaptic response;
• Spines can grow or shrink; New proteins.
 Integration of Brain Potentials
• Most recordings are extracellular, or
  outside brain. Averages across many or
  millions of neurons.
• Electrode size and distance determines
  how many neurons are measured.
• Human studies are mainly from surface of
  brain. Brain-waves are correlated with
  thoughts (Dreams, meditation, stimuli).
          Human Potentials
• Strong potentials in muscles--EMG, ECG
  (electromyogram and electrocardiogram).
• Weaker potentials from brain--EEGs.
• Evoked potentials allow study of changes.
• Computer averaging allows study of deep
  brain potentials: Event-related potentials in
  sensory systems and cognition.
EEG and ERP
       Electroencephalogram
• Shows widespread activity of brain, mainly
  from PSPs.
• Sleep stages, waking, slow wave, REM.
• Most intense in seizures of different types,
  petit mal, grand mal etc.
• Can find lobes that are most active (e.g.,
  occipital for alpha waves, temporal or
  frontal lobe or for seizures).
     Event-Related Potentials
• Warning and CNV: Cortex mainly.
• I-VI : Brain stem auditory paths.
• No-P3 : Cortical processing of auditory
  stimulus. Primary to association areas.
• Temporal resolution better than spatial
  resolution.
• Brain imaging (fMRI) localizes thoughts
  better, but not to neurons.