Lecture 16: Postsynaptic Potentials

What is an EPSP?

transient depolarization of postsynaptic membrane potential by presynaptic release of neurotransmitter at Gray type I excitatory synapse

What makes a slow EPSP?

glutamate binds to a metabotropic receptor, which activates the GPCR pathway, and then triggers an EPSP

What makes a fast EPSP?

1. glutamate binds to the NMDA receptor, which releases the MG²⁺ block, allowing glutamate to enter the cell.

2. after glutamate binding to the AMPA receptor, Na⁺ enters the cell and K⁺ leaves the cell

What is the delay time for a fast EPSP last?

30 ms

What is the delay time for slow EPSP last?

minutes

What does the duration of an fast EPSP depend on?

time during which transmitter is bound to the receptor

What causes a slow EPSP?

changes in the metabolism of the second messenger systems

What does decay of a slow EPSP depend on?

cAMP breakdown and dephosphorylation of the receptor

How was the fast EPSP in CA1 neurons of the hippocampus found?

whole-cell patch clamp recording of EPSC from a postsynaptic CA1 neuron under voltage clamp mode upon stimulating the Schaffer Collateral axons of presynaptic glutamatergic CA3 neurons in the presence of Strychnine (GlyR antagonist), Picrotoxin (GABA_A receptor)

What is the equation for a fast EPSC?

Fast EPSC = I_AMPAR + I_NMDAR

What happens during CA3 axon negative stimulation?

NMDAR receptors have the Mg²⁺ blocker

What happens during CA3 axon positive stimulation?

NMDA receptor loses the Mg²⁺, and Ca²⁺ and Na⁺ enter the cell along with glutamate

What happens in the presence of APV (an NMDAR antagonist)?

APV blocks NMDAR, so there will be no EPSC

What is true of the peak of NMDAR?

it is the same with or without APV

What is true of the green trace of NMDAR receptors?

it is a late/slow NMDA-mediated EPSC

What is true of the Mg²⁺ block?

it is intact at hyperpolarized membrane potentials

Why is the EPSC the same with and without APV?

because NMDAR is closed

What does NBQX block?

early/fast AMPA-mediated EPSC

Describe an EPSP.

a weak stimulus to the afferent nerve recruits only a few axons, resulting in a subthreshold EPSP recorded at the soma

Describe an action potential.

a strong stimulus recruits more axons, driving the EPSP recorded at the soma toward its reversal potential, which is beyond the AP threshold (-55 mv), leading the an AP

What is an IPSP?

transient hyperpolarization of postsynaptic membrane potential caused by presynaptic release of neurotransmitter GABA or Glycine at Gray type II synapses

What do GABA_A receptors cause?

net influx of Cl^- that hyperpolarizes the cell

What do GABA_B receptors activate?

they activate their effectors (K⁺ channels), leading to a net efflux of K⁺ that hyperpolarizes the cell

How was the GABAergic IPSP in CA3 neurons of the hippocampus found?

Whole-cell patch clamp recording of inhibitory postsynaptic potential (IPSP) from a postsynaptic CA3 neuron under current clamp mode upon stimulating the mossy fiber axons of presynaptic dentate gyrus neurons in the presence of CNQX (AMPAR and KAR antagonist) and APV (NMDAR).

What does stimulation of mossy fibers cause?

fast initial IPSP mediated by Cl^- influx through GABA_AR, followed by slower IPSP mediated by GABA_BR activation and subsequent opening of K⁺ channel

What doe IPSP decrease?

the ability of the membrane potential to reach AP threshold