The action potential (what 'firing' means)

• Basic bio/chem


  cells have semi-permeable membranes

  • protein channels are embedded into the membrane
  • some channels are specific
  • can be open or closed
  • inside and outside the cell are ions:
  • Na+, K+, Ca2+, Cl-

  Ions move down gradients

  • concentration (diffusion); want to move to where there are less of them
  • electrical; want to move where the charge is opposite
• sodium-potassium pump


  Active (energetic) transport of

  • sodium out of cell
  • potassium into cell
  • more Na+ than K+ (3;2)
  • causes a concentration gradient
  • K+ ions want to leave
  • Na+ ions want to enter
• Resting potential


  membrane does not let most ions through

  • K+ channels partly open; Na+ channels close

  inside of cell is negatively charged

  • Na+/K+ pump is running
  • cell contains negative proteins
  • resting potential = -65mV

  ion face gradients

  • Na+ ions
  • concentration gradient: IN
  • electrical gradient: IN
  • K+ ions
  • concentration gradient: OUT
  • electrical gradient: IN
• Ion channels


  3 types:

  • Na+/K+: active (require energy)
  • K+ channels: partly open during resting potential
  • Na+ channels: close during resting potential, can close 2 ways
  • activation gate or inactivation gate

  Channels can be voltage-gated

  • the voltage across membrane can open or close the channel
  • Na+, K+ channels are voltage gated
• Voltage-gating


  external stimulation makes it less negative

  • depolarization

  Channels open/close

  • K+ channels
  • partly closed at resting potential
  • open at high voltages
  • Na+ channels
  • activation gate:
  • closed at resting potential
  • open at higher voltages
  • inactivation gate:
  • open at resting potential
  • closed at very high voltages
• Action potential


  cell has threshold

  • depolarization below threshold dies out
  • depolarization above threshold leads to:

  1. voltage gated Na+ channels open
  2. Na+ floods in
  3. voltage rises, fast
  4. Na+ channels close, K+channels open
  5. K+ channels and pump restore resting voltage
  6. most K+ channels close
• Action potential propagation; the party analogy

  • house #1 is having a party
  • front door (Na+ channels) open for guests
  • guests in backyard spill over into house #2 yard
  • diffusion of Na+ ions inside axons
  • House #2 decides to have party (depolarization)
  • they open their door (Na+ channels)
  • house #1 residents get tired, go to bed, lock doors
  • Na+ channels inactivated, refractory period
  • party in #2 yard spills over to house #3
  • but not house 1 since doors r locked
  • party moves down street
• Myelin

  • excluded by Schwann cells (PNS) or oligodendrocytes (CNS)
  • covers axon, except nodes of Ranvier
  • enables faster saltatory conduction
  • party analogy
  • house #2 gets abandoned
  • guests from #1 cross #2 yard to #3
  • no need to wait for house #2 party to get going and only then move to #3
• EPSPs and IPSPs


  testing neuronal communication

  • stimulate presynaptic axon
  • measure from postsynaptic soma

  results:

  • at excitatory synapse: excitatory post synaptic potential (EPSP)
  • at inhibitory synapse: Inhibitory post synaptic potential (IPSP)
• EPSP & IPSP mechanism


  ESPS are too weak to cause an action potential

  • cell returns to resting potential

  ESPS

  • depolarization causes some Na+ channels to open
  • some Na+ enters but not enough to open more voltage-gated Na+ channels
  • channels close when stimulation ends
  • Na+/K+ pump restores resting potential

  IPSP

  • stimulation opens K+ or Cl- channels
  • K+ leaves or Cl- enters; cell hyperpolarizes
  • channels close when stimulation ends
  • Cl- diffuse out; Na+/K+ pumps helps
• Temporal summation


  Multiple EPSPs arriving soon after each other

  • EPSP 1 arrives; cell depolarizes slightly
  • cell begins to repolarize
  • EPSP 2 arrives; cells depolarizes to high voltage

  if summed EPSPs exceed cell threshold:

  • cell polarization high enough to open Na+ channels
  • action potential

  EPSPs can also sum with IPSPs
• Spatial summation


  EPSPs arriving at same time from different synapses (different axons)

  • not necessarily from the same presynaptic neuron
• response specificity

  • makes a neuron that only responds to light moving in one direction
• rate of firing


  most neurons have spontaneous firing rate

  • fire with no external stimulation
  • at a constant rate (more or less)

  synapses are not only on/off

  • can fire at different rates
  • rate of firing can be part of the message

  IPSPs can decrease the rate of firing, EPSPs can increase
• control mechanisms in the brain


  almost all behaviour results from:

  • communication between neurons
  • + the mysterious role of glia

  brains need to do many different things:

  • see, run, throw things, dream, speak, play

  control mechanisms:

  • excitatory, inhibitory neurons in complex circuits
  • more/less dendritic spines
  • different activation thresholds
  • different numbers of ion channels
  • different spontaneous rates/ changes in rate
  • differences at the synapse
• synapses

  • where the action is
  • connections between the neurons
  • presynaptic neuron -> axon terminal (bouton)
  • postsynaptic neuron -> dendrite/soma
  • require a different form of communication
  • chemical (not electric)
  • there are also electric synapses
• structure of synapses

  • pre and post synaptic cells do not touch
  • presynaptic cell releases chemicals (neurotransmitters) that affect the postsynaptic cell
• importance of glia

  • most synapses are wrapped in astrocyte (type of glia) processes (tentacles)
• overview of synaptic transmission

  1. neurotransmitters synthesized
  2. action potential arrives
  3. voltage-gated channels Ca+ channels open; Ca+ enters
  4. neurotransmitters released into synaptic cleft
  5. transmitter molecules attach to postsynaptic receptors
  6. ligand-gated ion channels open
  7. depolarization of post-synaptic cell

  OR

  6. G-protein receptors activate downstream pathways

  7. enzymes in postsynaptic soma cause depolarization
• The action potential arrives

  • action potential moves down axon
  • at terminal bulb (bouton), depolarization opens voltage-gated Ca+ channels:
  • Ca+ enter cells
  • vesicles containing neurotransmitters fuse with membranes
  • neurotransmitters spills into synaptic cleft
• vesicles fusion

  • its complicated
  • vesicles have membranes (like cells)
  • Ca+ directly causes vesicle fusion
  • vesicles are recycled
  • there are lots of vesicles
  • only a small fraction released at each event
• ionotropic receptors

  • are ion channels
  • ligand-gated: binding the neurotransmitters opens them
  • channel usually admits:
  • positive ions (Na+, K+,Ca+; excitatory); glutamate
  • Cl- (inhibitory); GABA
  • neurotransmitter detaching closes channel
  • channel opening allows ions into postsynaptic cell, directly depolarizes it
  • fast (1 ms from binding to opening)
  • short lasting (5 ms to closing)
• metabotropic receptors

  • are G-protein coupled proteins
  • activated by binding of neurotransmitters
  • cause lots of downstream effects inside the cell
  • enzymes inside the cell open ion channels
  • ions enter, depolarize cell
  • lots of different neurotransmitters
  • dopamine, serotonin
  • slow (30 ms from binding to opening)
  • long lasting (few secs up to many years)
• reuptake

  • neurotransmitters left in synaptic cleft
  • would reactivate receptors if left there
  • needs to be removed or recycled
  • broken down (acetylcholine, by the receptor)
  • presynaptic cell reabsorbs it. reuptake
  • active transport channels. transporters
  • astrocytes (and other glia) absorb transmitter
• need for speed

  • synapses need to be fast
  • sensory info has to be acted on quickly
  • lots of synapses (100-500 trillion)
  • vesicles wait in the active area (Ca+ fuses the vesicle directly)
  • synaptic cleft is small (20-30 nm)
  • diffusion takes 0.01 ms
  • ionotropic receptors
  • depolarize the postsynaptic cell immediately
• Neuronal communication

  Cell A:

  • action potential (depolarization) moves down axon
  • reaches bouton. voltage-gated Ca+ channels open
  • Ca+ enters cell. activates vesicles
  • vesicle fuse with cell membrane
  • neurotransmitter spills into synaptic cleft

  Cell B:

  • receptors bind neurotransmitter
  • binding channels shape protein; channels opens
  • ions enter cell. depolarize cell (EPSP)
  • more EPSPs (temporal or spatial) increase depolarization
  • cell B has an action potential, which moves down the axon