Select the correct statement(s) regarding the action potential

a) Voltage-gated Na channels activate in response to depolarization, and inactivate approximately 0.5 ms later.

b) Voltage-gated K channels possess both activation and inactivation gates, which underlie the absolute and relative refractory periods.

c) Deactivation of voltage-gated K channels occurs around the peak of the action potential.

d) Removal of inactivation of voltage-gated Na channels, which occurs upon repolarization of the membrane, marks the end of the relative refractory period.

e) The after hyperpolarization (AHP) is due to K channel activation, and imposes a insurmountable restriction on generation of a new action potential.

Lectures 7-8: Synaptic Transmission I and IILectures 7-8: Synaptic Transmission I and II

Reading: Ch 4, section: synapses and neuronal integration

Neuronal Morphology

(soma)

Synapses are highly specialized site of close contactbetween two cells (often neurons).

Synaptic transmission is the primary means ofrapid inter-neuronal communication in the brain.

Presynaptic axon initiates the signal.

Postsynaptic (target) cell receives the signal.

Postsynaptic targets can be a muscle, gland or another neuron.

Synapses - junction between two neurons, or between a neuron and a muscle or gland that enables one cell to electrically and/or biochemically influence another cell.

2 types - electrical synapse- chemical synapse

Electrical Synapse - a direct electrical connection between two cells, formed by a gap junction.

Gap Junctions – made up of multiple proteins called connexins

The small diameter of the “tunnel” in a gap junction permits water-soluble particles (such as ions) to pass between cells but blocks the passage of larger molecules.

First Example of an Electrical Synapse

Furshpan and Potter, 1959

Discovered in the crayfish nervous system by Ed Furshpan and David Potter

brief 0.1 msec synaptic delay

Chemical Synapse - anatomical junction between two neurons, or between a neuron and a muscle or gland where a chemical neurotransmitter is released.

- presynaptic neuron

- synaptic cleft

- postsynaptic neuron

- neurotransmitter

- postsynaptic receptor

Components:

Sequence of events - chemical synapse

Presynaptic Release - synaptic vesicles - voltage-gated Ca++ channels

Postsynaptic Response - postsynaptic receptors - postsynaptic potential (PSP)

Excitatory postsynaptic potential (EPSP)

- depolarizing potential that brings Vm towards threshold for generation of an action potential

(i.e. the equilibrium potential of the synaptic current is more positive than the resting potential)

- most common excitatory neurotransmitters are glutamate (Glu) and acetylcholine (Ach)

Inhibitory postsynaptic potential (IPSP)

- hyperpolarizing potential that brings Vm away from threshold for generation of an action potential

(i.e. the equilibrium potential of the synaptic current is more negative than the resting potential)

- most common inhibitory neurotransmitters are gamma-amino-butyric acid (GABA) and glycine (Gly)

Neuromodulator - transmitter that activates 2nd messenger system

2nd messenger system - binding of neurotransmitter to G-protein coupled postsynaptic receptor triggers the enzymatic synthesis of molecules with widespread secondary actions (i.e. cAMP).

Some key neuromodulators:

Dopamine

Serotonin

Transmitter removal

- degradation - enzymatic breakdown (AchE)

- transport - active transport back into the presynaptic cell - “reuptake”

- diffusion - the transmitter simply diffuses away from the synaptic terminal

Examples of drug actions on:

transmitter release - tetanus toxin blocks vesicular fusion

transmitter uptake

- Cocaine blocks the reuptake of dopamine

- SSRIs (paxil, prosac, zoloft) block the reuptake of serotonin

transmitter removal - many insecticides block the degradation of ACh

transmitter binding

- Curare blocks the postsynaptic action of ACh at the neuromuscular junction

- THC is an agonist for the endogenous cannabinoid receptor

Synaptic Interactions and Neuronal Integration

convergence - the synaptic input of many neurons on to one neuron

divergence - the synaptic output of one neuron onto many neurons

temporal summation - the additive effect of PSPs occurring close together in time

spatial summation - the additive effect of PSPs occurring together on nearby parts of the same cell

presynaptic inhibition - synaptic inhibition of a synaptic terminal causing a decrease in transmitter release

Examples

Concepts:

Convergence - the synaptic input of many neurons on to one neuron

Divergence - the synaptic output of one neuron onto many neurons

R1

R2

Stimulate Ext1

Stimulate Ext1

Temporal summation

Stimulate Ext1

Stimulate Ext1

R1

R2

No summationR1

R2

Ext1

Ext2

Ext3Inh1

3 excitatory synapses: Ext1, Ext2, Ext31 inhibitory synapse: Inh12 recording sites: R1, R2

On average, each neuron receives ~ 1,000 synapses Modified version of textbook figure

R1

R2

Ext1

Ext2

Ext3Inh1

3 excitatory synapses: Ext1, Ext2, Ext31 inhibitory synapse: Inh12 recording sites: R1, R2

On average, each neuron receives ~ 1,000 synapses

R1

R2

Stimulate Ext1

Stimulate Ext2

Spatial summation

Stimulate Ext1

R1

R2

No summation

Ext3

Modified version of textbook figure

Stimulate Ext1 & Inh1

R1

R2

No summation

R1

R2

Stimulate Ext3 and Inh1

EPSP-IPSP cancellation

R1

R2

Ext1

Ext2

Ext3Inh1

3 excitatory synapses: Ext1, Ext2, Ext31 inhibitory synapse: Inh12 recording sites: R1, R2

On average, each neuron receives ~ 1,000 synapses Modified version of textbook figure

presynaptic inhibition - synaptic inhibition of a synaptic terminal causing a decrease in transmitter release

Synaptic Transmission Experiment

Red dots ( ) indicate the location of 10 synapses, each of which causes a small EPSP in the dendrite of the postsynaptic neuron.

When all 10 synapses are activated simultaneously by stimulation of their presynaptic axons, the summed EPSP ‘felt’ at the axon hillock is well above threshold for firing a spike in the postsynaptic neuron.

Consider three cases:(1) The presynaptic axons are simultaneously activated while the voltage-gated Na and K channels in the postsynaptic neuron are inactivated with a toxin. The postsynaptic response reflects synaptic transmission only, i.e. the EPSP.

(2) The presynaptic axons are not stimulated. A brief current pulse is delivered to the postsynaptic cell via the recording electrode. This current pulse evokes a spike in the postsynaptic cell. This postsynaptic response reflects the spike only.

(3) The presynaptic axons are stimulated in the absence of any blockers. This postsynaptic response reflects the EPSP and the postsynaptic spike it triggers. Recording site for data

displayed on next page

Case 1 - EPSP only Case 2 - Spike only

Case 3 - Both EPSP and spike(physiologically normal condition)

Stimulus = presynaptic stimulation Stimulus = postsynaptic shock

Stimulus = presynaptic stimulation

All three experiments superimposed for comparison (could not actually occur simultaneously)

SUMMARY1) Electrical Synapses

a) direct connection between two cells, the Gap Junctionb) small molecules including charged ions can pass freely

between the two cellsc) synaptic delay is extremely short.

2) Chemical Synapsesa) presynaptic cell and postsynaptic cell are closely opposed to each other, separated by a synaptic cleftb) sequence of events:

- presynaptic AP leads to an influx of Ca++

- Ca++ triggers the release of neurotransmitter by exocytosis- neurotransmitter diffuses across the cleft to the postsynaptic cell binds to receptors that open ion channels

3) Concepts of convergence, divergence, temporal/spatial summation