lecture 6 - postsynaptic potentials and summation

what do neurotransmitters do

bind to receptors on the postsynaptic membrane

what is the function of the receptor

it determines what happens INSIDE the cell

the neurotransmitter never enters the cell

what happens in the post synaptic cell

post synaptic channel current causes an excitatory or inhibitory AP in the post synaptic cell

what happens to the neurotransmitter after it binds to the receptor

it is removed from the cleft by glial cells or enzymatic degradation

lock and key analogy

the receptor is the lock, the neurotransmitter is the key

ionotropic receptors

ligand gated ion channels

NT binding directly opens/closes channel causes current flow to product postsynaptic potentials

fast (10ms)

metabotropic receptors

GPCRs

NT binding indirectly affects ion channels, either opens or closes a channel

slow (100 ms)

G proteins

alpha, beta, and gamma subunit

glutamate channels

permeable to Na+ and sometimes Ca2+

2 main types: AMPA or NMDA receptors (we focus on AMPA)

4 subunits, with at least 2 types of subunits

pore in the middle of subunits

always excitatory, they depolarize bc they are permeable to sodium

four main features of AMPA

activated by glutamate

excitatory response

mainly NA+, K+ conductance

found in synaptic cleft

What is an EPSC

excitatory post synaptic current

the current change after an excitatory neurotransmitter activates a receptor

fast active, short-lived

creates depolarization

what is EPSP

excitatory post synaptic potential:

the potential caused by an EPSC

how does the AMPA receptor reconcile being permeable to both Na+ and K+

driving force = membrane potential - equilibrium potential

for potassium, DF = Vm - Eion = +20 so it leaves

for sodium, DF = Vm - Eion = -120 so it comes in

the sodium current is way stronger than the potassium current

GABA receptors

external binding site for GABA

5 subunits of at leat 2 diff types and a pore

permeable to chloride

four characteristics of GABA A-type receptors

GABA binding required

permeable to Cl- ions

IPSP: inhibitory postsynaptic responses: Cl- hyperpolarizes

fast acting, short lived

synaptic location

modulated by drugs (Benzodiazepines, Barbiturates, Alcohol)

Graded potentials

decrease in strength as they spread from point of origin

proportional to the intensity of the stimulus

where are metabotropic receptors

- presynaptic - modulate neurotransmitter release; act on Ca2+, K+, snare complex

- perisynaptic - next to the synapse

- postsynaptic - modulate postsynaptic potential; affect ionotropic receptors and K+ channels

- way far away from the dendrite - modulate neural excitability; act on leak and voltage gated channels

g proteins would close ~20% of K+ leak channels; MP depolarizes

GABA receptors (B-type)

metabotropic

GABA binding required

activate K+ channels through a G-protein cascade

IPSP: inhibitory post synaptic responses (hyperpolarizing)

slow acting, long-lasting

perisynaptic locations, both pre and post synaptic sides of synapse

presynaptic GABA type - b receptors

inhibit neurotransmitter release

negative feedback

how to presynaptic metabotropic receptors block vesicle release

- block voltage gated calciun channels at the axon terminal

- interfere with SNARE protein function

- block enzyme pathways necessary for vesicle docking

what must happen for a neuron to fire

the AXON HILLOCK must reach threshold

how can a neuron fire if each input is so small

the soma integrates + sums the information it receives to create a large enough potential to get to threshold

each neuron can get 100s-1000s of inouts

spatial summation

- adding inputs over space/location (multiple inputs at once to different spines)

temporal summation

adding inputs at the same location over time (multiple inputs over time to the same spine)

it has to happen faster than the graded potential can decay

inhibitory inputs also summated

membrane potential at the hillock is the sum of all EPSPs and IPSPs recieved at once

which synapses have the most impact and why

synapses closer to the axon hillock because the graded potential decays more for more distal dendrites

how are neurotransmitters removed from the synapse (3 ways)

- enzymatic degredation (sometimes products are reused and/or recycled)

- reuptake into the axon terminal

- for NT diffused out of the synaptic cleft: another type of reuptake into astrocytes