Lecture 16: Postsynaptic Potentials

What is an EPSP?

an excitatory postsynaptic potential; it is a transient depolarization of the postsynaptic membrane caused by neurotransmitter release at an excitatory synapse—making an action potential more likely

What is an IPSP?

an inhibitory postsynaptic potential; it is a transient hyperpolarization of the postsynaptic membrane caused by inhibitory neurotransmitters—making an action potential less likely

How does an EPSP affect membrane potential?

it depolarizes the membrane and moves it closer to threshold

How does an IPSP affect membrane potential?

it hyperpolarizes the membrane and moves it farther from threshold

What is the functional difference between EPSPs and IPSPs?

EPSPs increase neuronal excitability whereas IPSPs decrease neuronal excitability

What are the fast EPSP receptors?

• NMDA

• AMPA

What is the slow EPSP receptor?

metabtropic receptor

What is the synaptic delay for fast and slow EPSPs?

• fast: 30 ms

• slow: minutes

What are ionotropic receptors?

ligand gated ion channels

True or False: The duration of EPSP depends on the time during which transmitter is bound to the receptor.

true

Briefly describe metabotropic receptors (GPCRs).

• caused by changes in the metabolism of the second messenger systems

• decay of EPSP here depends on cAMP breakdown and dephosphorylation of the receptor

Why can slow EPSPs persist for long periods?

they involve phosphorylation and intracellular signaling pathways

What is a synaptic delay?

the brief delay between neurotransmitter release and the postsynaptic response

Which neurotransmitter is responsible for the EPSPs discussed in hippocampal CA1 neurons?

glutamate

True or False: Whole-cell patch clamp recording of excitatory postsynaptic current (EPSC) from a postsynaptic CA1 neuron under voltage clamp mode upon stimulating the Schaffer Collateral (SC) axons of presynaptic glutamatergic CA3 neurons in the presence of Strychnine (GlyR antagonist) and Picrotoxin (GABA_A receptor).

true

Which two receptor types contribute to glutamatergic EPSPs?

AMPA receptors and NMDA receptors

What does EPSC stand for?

excitatory postsynaptic current

Under what experimental condition is EPSC measured?

voltage clamp

What is the equation for the fast EPSC?

fast EPSC = I_AMPA + I_NMDA

Which receptor contributes most to the early peak EPSC?

AMPA receptors

Which receptor contributes most to the later EPSC?

NMDA receptors

Which antagonist blocks NMDA receptors?

APV

What happens to the late EPSC when APV is applied?

the late component disappears

What conclusion can be drawn when APV eliminates the late EPSC?

the late EPSC is mediated by NMDA receptors

What ion blocks NMDA receptors at hyperpolarized membrane potentials?

Mg²⁺

Why is the peak EPSC similar with and without APV at -80 mV?

NMDA receptors are already blocked by Mg²⁺

What two conditions are necessary for NMDA receptor activation?

glutamate binding and membrane depolarization

Why are NMDA receptors called coincidence detectors?

they require both ligand binding and depolarization simultaneously

Which receptor is primarily responsible for the slow component of a glutamatergic EPSC?

NMDA receptors

Which receptor is primarily responsible for the fast component of a glutamatergic EPSC?

AMPA receptors

What is a reversal potential?

the membrane potential at which there is no net ion current through a channel

What happens to current when membrane potential exceeds the reversal potential?

current changes direction

Why does inward current become outward current at positive voltage?

the driving force on ions reverses

Are EPSPs graded or all-or-none?

graded

Are action potentials graded or all-or-none?

all-or-none

What happens when an EPSP remains below threshold?

no action potential is generated

What happens when an EPSP reaches threshold?

an action potential is generated

Approximately what threshold voltage is shown in the lecture?

about -55 mV

Which neurotransmitters commonly produce IPSPs?

• GABA

• glycine

What are the two major forces of GABA receptors discussed?

• GABA_A

• GABA_B

Which receptor produces fast IPSPs?

GABA_A receptors

Which receptor produces slow IPSPs?

GABA_B receptors

What type of receptor is GABA_A?

ionotropic receptor

Which ion channel is associated with GABA_A receptors?

a chloride channel

Which ion movement occurs through GABA_A receptors?

Cl- influx

What effect does Cl- influx have on membrane potential?

hyperpolarization

What does the early IPSP represent in hippocampal recordings?

GABA_A-mediated inhibition

At which equilibrium potential does the early IPSP reverse?

E_Cl

What does reversal at E_Cl indicate?

chloride ions carry the current

What type of receptor is GABA_B?

a metabotropic GPCR

How does GABA_B receptor activation produce inhibition?

through G proteins that activate potassium channels

Which ion movement is associated with GABA_B-mediated IPSPs?

K+ efflux

What effect does K+ efflux on membrane potential?

hyperpolarization

What does the late IPSP represent in hippocampal recordings

GABA_B-mediated inhibition

At which equilibrium potential does the late IPSP reverse?

E_K

What does reversal at E_K indicate?

potassium ions carry the current

What are mossy fibers?

excitatory projections from the dentate gyrus granule cells to the hippocampus

Which neurotransmitter do mossy fibers release?

glutamate

What neuronal population provides inhibition to CA3 neurons?

GABAergic interneurons

What is feed-forward inhibition?

an excitatory neuron activates an interneuron, which then inhibits a downstream neuron

What is the major postsynaptic target of mossy fibers?

CA3 pyramidal neurons

What does CA3 stand for?

Cornu Ammonis area 3 of the hippocampus

Are CA3 pyramidal neurons excitatory or inhibitory?

excitatory neurons

What neurotransmitter do CA3 pyramidal neurons primarily use?

glutamate

Besides CA3 pyramidal neurons, what other neurons are activated by mossy fibers?

GABAergic interneurons

What neurotransmitter is released by hippocmapal interneurons in the lecture circuit?

GABA

Are GABAergic interneurons excitatory or inhibitory?

inhibitory

Why is activation of interneurons important in the mossy fiber circuit?

they provide inhibition to CA3 pyramidal neurons

Describe feed-forward inhibition in the mossy fiber circuit.

mossy fibers excite GABAergic interneurons, which then inhibit CA4 pyramidal neurons

What is the functional rest of feed-forward inhibition?

it limits excessive excitation of CA3 neurons

Why might the hippocampus use feed-forward inhibition?

to control excitability and prevent runaway excitation within hippocampal circuits

What axons were stimulated during the IPSP experiment?

mossy fiber (mf) axons

From which neuron was the IPSP recorded?

a postsynaptic CA3 neuron

Was the recording performed in voltage clamp or current clamp?

current clamp

Why were CNQX and APV included in the experiment?

to block excitatory glutamatergic transmission

What receptors does CNQX block?

AMPA receptors and kainate receptors

What receptors does APV block?

NMDA receptors

Why block all glutamate receptors in lecture’s experiment?

to isolate inhibitory synaptic responses (IPSPs)

If glutamate receptors are blocked, why is stimulation of mossy fibers still able to produce an IPSP?

mossy fibers activate GABAnergic interneurons, which then release GABA onto the recorded CA3 neuron

What synapse is ultimately being studied in the IPSP experiment?

the inhibitory synapse between a GABAergic interneuron and a CA3 pyramidal neuron

Why is the IPSP considered disynaptic?

mossy fibers first activate an interneuron, and the interneuron then inhibits the CA3 neuron