nerve/synapse lectures 5-6 Flashcards
what is presynaptic terminal
swelling at end of axon
includes active zone
what is active zone
specialized region
vesicles parked here in active zone
held in place
faces postsynaptic spine
what are presynaptic vesicles
presynaptic terminals filled with presynaptic vesicles
made out of plasma membrane
packages neurotransmitter - chemical released by presynaptic terminal
what is synaptic cleft
name of gap between presynaptic terminal and postsynaptic spine
what is postsynaptic density
in post synaptic membrane
looks dark - many proteins
high density of proteins involved in process of transmitting info from presynaptic terminal to postsynaptic spine
what triggers neurotransmitter release in presynaptic terminal
activation of voltage gated calcium channels
ion channels are next to docked synaptic vesicles
what are ligand gated ion channels
postsynaptic receptors for transmission at brain synapses
describe ligand gated ion channels
ion channels open up pore when binds a small messenger molecules
released by presynaptic terminal and activates ion channel in postsynaptic spine
what are ligand gated ion channels AKA
neurotransmitter receptors
ionotropic receptors (since they are ion channels)
what does calcium do
biochemical signal and causes cell to do things
can cause cells to contract (biochemical signal in skeletal muscle)
triggers sequence of biochemical events in presynaptic terminal
describe calcium levels inside and outside cell
outside cell = low concentration
inside cells and presynaptic terminal = veryyyyy low, so calcium wants to flow in down concentration gradient
do neurons want to keep calcium levels high inside the cell
wants to keep calcium levels in cell low because calcium is a signalling molecule
describe the types of signal transformations during synapse
ap = electrical signal then gets to presynaptic terminal and is converted to chemical signal = neurotransmitter and then converted back to electrical signal in postsynaptic cell
name the 3 main steps of chemical synaptic transmission
1 = ap invades presynaptic terminal, calcium channels open and result in calcium influx into terminal
2 = synaptic vesicles fuse with presynaptic membrane releasing transmitter into synaptic cleft
3 = transmitter diffuses across the cleft and activates receptors in postsynaptic membrane
describe step 1 of chemical synaptic transmission
wave of depolarization depolarizes presynaptic terminal and gets more positive
causes voltage gated calcium channels to open
calcium levels increase, small amount flowing in changes the concentration significantly
calcium binds to proteins found in presynaptic terminal and activates them and sequence of biochemical events, so a few vesicles docked in active zone will fuse to PM and open and dump contents (neurotransmitter) into cleft
describe step 2 of chemical synaptic transmission
neurotransmitter in cleft
binds to ligand gated ionotropic neurotransmitter receptors and causes ion channels to open and changes electrical properties of postsynaptic cell
what is the fusion of a synaptic vesicle at an active zone dependent on
calcium
the postsynaptic response to neurotransmitter is either what (name and describe - 2)
EPSP = excitatory postsynaptic potential, depolarizes postsynaptic membrane
IPSP = inhibitory postsynaptic potential, hyperpolarizes postsynaptic membrane
describe excitatory synapses (EPSP)
on spines
makes postsynaptic cell more likely to fire an ap
closer to ap threshold, depolarizes
describe inhibitory synapses (IPSP)
on dendritic shaft
makes postsynaptic cell less likely to fire an ap, hyperpolarizes postsynaptic cell and pushes away from ap threshold
what is the main excitatory neurotransmisster in brain
glutmate (an amino acid)
what is monosodium glutmate
MSG
can have effects if too much since glutamate is a biologically active neurotransmitter
what is rapid excitatory transmission at synapses due to
actions of glutamate on 2 types of ionotropic glutamate receptors = AMPA and NMDA receptors
describe NMDA and AMPA receptors
both in postsynaptic spine
ion channels that open in response to binding of small molecules (like neurotransmitters) to receptor sites on their external surfaces
what are AMPA receptors responsible for
fast EPSP at excitatory synapses
describe AMPA receptors creating EPSP
calcium flows into presynaptic terminal
docked glutamate vesicles will fuse and dump glu into cleft and binds to AMPA receptor in postsynaptic cell and opens ion channel
pore is permeable to sodium, so sodium flows in and depolarizes
what is EPSP
small transient depolarization of the postsynaptic spine
depolarization is super short, a few milivolts and lasts around 20msec (long compared to ap)
just brings it a bit closer to threshold
in typical brain synapses
depolarization causes by a single EPSP is > (or equal to) a few milivolts and lasts around 20msec
is the depolarization caused by a single EPSP large enough to depolarize initial segment to threshold
NOOOO too small
need around 50-100 epsps
neuron usually has many synapses, most are excitatory EPSP and many of these happen at same time
they add to each other and drives postsynaptic cell to ap threshold
does ap happen in dendrites
nooo
depolarization spreads passively and can add together = depolarizes initial segement
how many epsps must sum at initial segment to initiate ap
50 to 100
what can the near simultaneous epsps come from
multiple synapses acting in synchrony
individual synapses activated at high frequencies
what are the 2 key properties of NMDA receptors
at resting membrane potential the pore is blocked by magnesium, depolarization expels magnesium and enables pore to conduct
open pore is highly permeable to calcium and monovalent cations
describe NMDA receptors at resting potential
pore plugged by mg
so will not react when glu arrives
also need glycine (along with glu)
describe NMDA receptors at threshold potential
if membrane is depolarized = mg comes out since the inside is not as negative, and magnesium is attracted to the negatives, unplugs and allows calcium to flow
opens and makes pore for calcium and flows into presynaptic cell and triggers biochemical events in spine
what does NMDA receptor act as
Coincidence receptor
what is a coincidence receptor
detects 2 things happening at same time
detects presynaptic neuron released glutamate and postsynaptic cell is already depolarized
if these 2 things happen at same time = NMDA receptor can conduct calcium into cell
what happens at -70mv and if postsynaptic membrane is depolarized
at -70mv, almost all synaptic current at an excitatory glutamate synapse is carried by Na+ through AMPA receptors
if postsynaptic membrane is depolarized a substantial calcium current flows through NMDA receptors
what is synaptic plasticity
high active excitatory synapses become stronger
epsps become larger
involves NMDA receptors
how do you learn things
synapses which get stringer
ex = learn a new word, connections between the word and meaning become stronger by specific synapses becoming stronger, pathways become stronger
what is LTP (long term potentiation)
Experimental protocol
records epsps in postsynaptic neuron and puts electrode to simulate presynaptic neuron
send an ap = 1 test pulse and then stimulate presynaptic membrane a bunch
what happens when burst of aps (LTP)
high frequency activity depolarizes postsynaptic spine, removes magnesium block of NMDA receptor and enables them to conduct calcium
lots of glutamate released, induction phase
what happens hours after induction of LTP
epsps are larger
send a single test pulse = will be larger than initial
synapse will have greater influence on if cell fires ap
many effects can happen
what are the 3 steps/summary of LTP
control
induction
LTP
what is excitotoxicity
high concentrations of glutamate is toxic to neurons
Phenomenon thought to involve calcium influx through NMDA receptors
what is glutamate
also a neurotoxin
brain must regulate carefully
what happens if too much glu
neurons get way too depolarized and lots of calcium flows into and if calcium is super high cell with die
describe effect of msg
adults have blood brain barrier so glutamate will not get into brain
but in babies = not developed and more susceptible to excitotoxicity
(in olden days, msg would be in baby food since moms would taste and be like yum, so good for baby)
describe effect of stroke
no oxygen to regions of brain and neurons die (1st phase of neurodegeneration) and release much glu and diffuses to other neurons and diffuses out of localized region where stroke happened into surrounding areas (penumbra) and too much depolarization and cells die too (2nd phase of neurodegeneration)
what is excitotoxicity likely to contribute to
neuronal degeneration after stroke and in some neurodegenerative diseases
important in epilepsy
what is main inhibitory neurotransmitter in brain
gamma-aminobutyric acid (GABA)
what receptor is responsible for IPSPS
postsynaptic receptor GABA a receptor
describe GABA a receptors
GABA is in vesicles and is released and binds to post synaptic ligand gated ion channels GABA a receptors
open and form pore and changes electrical properties of post synaptic cell
what is GABA
neurotransmitter derived from amino acid
smal molecule
what type of receptor is GABA a
ionotropic
what does activation of GABA a receptor cause
influx of chlorine and hyperpolarizes postsynaptic membrane
inhibits post synaptic cell
what can GABA a receptors be acted on by
pharmacological agents
describe effects of benzodiazepines on GABA a
xanax and valium
mild tranquillizers
feel relaxed and sleepy
drugs bind to GABA a and potentiate, make receptor more sensitive to GABA enhances transmission to inhibitory synapses and causes more inhibition in brain and increased efficacy of inhibitory synapses
describe effects of barbiturates on GABA a
phenobarbital and pentobarbital
do same thing and act on GABA and makes inhibitory synapses stronger
stronger than benzodiazepines
has bigger effect on receptors and will just put you to sleep
describe effects of ethanol - alcohol on GABA a
makes you sleepy
acts on GABA a receptors
partly due to potentiating GABA a
do neurons receive both excitatory and inhibitory synapses
yesssss
some of each type
where are excitatory and inhibitory synapses located
excitatory = located on dendritic spines
Inhibitory = clustered on or near the cell soma, where inhibitory effect is maximal
whether or not neuron fires ap depends on…
relative balance of EPSPs and IPSPs
depends on relative amounts of excitatory vs inhibitory, shapes firing power of neuron and how it communicates
what is output of neuron
all or none firing of action potentials down axon
can a neuron be both excitatory and inhibitory
NOOO
excitatory or inhibitory
will only released GABA or glu from terminal, will not switch back and forth
give an ex of an inhibitory and excitatory neuron
pyramidal neurons = excitatory, release glu
perkinje = inhibitory, release GABA
describe how inhibitory neurons are stimulated to release GABA
must fire ap and to fire ap must have excitatory synapses on dendrites
drives ap to inhibit other neurons
what happens if there is no inhibition and just excitation
excitation takes over and feeds on itself = epileptic seizure, electrical storm in brain
inhibitory sculpts activity in nervous system and acts as break to control excitation
drugs that block GABA receptors can also cause seizures
what are. Metabotropic receptors (G-protein coupled receptors, GPCRs)
different family of neurotransmitter receptors
not ion channels
what do glutamate synapses have
ionotropic receptors = AMPA and NMDA
metabotropic glutamate receptors (mGluRs)
describe mGluRs
not ion channels
activated by glutamate
relays chemical signal to inside of postsynaptic neuron
what does activation of mGluRs generate
chemical signal called second messenger inside postsynaptic spine
changes conformation and becomes activated and initiates synthesis of 2nd messengers
receptor initiates biochemical events on inside of cell
what are 2nd messengers
transmit messages, build up in cell and can diffuse
concentrations build up and then can activate proteins inside of cell, ex like bind to ion channel and open it up and change electrical properties of post synaptic cell
what can 2nd messengers activate
ion channels
protein kinases
transcription factors
are metabotropic receptors fast
nooooooooo
slow to turn on and off
generation, diffusion and effects of small molecules can last long
describe 2nd messengers activating protein kinases
activate proteins
attaches phosphate groups to proteins
stick proteins to enzymes
changes biochemistry of cells
describe 2nd messengers activating transcription factor
activated transcription factor migrates into nucleus and regulates transcription/expression of new genes (regulation of genes)
what do glutamate and GABA activate
both ionotropoic and metabotropic receptors
glu = NMDA, AMPA and mGluRs
GABA = GABA b and GABA b
what is difference between GABA a and GABA b
a = ionotropic
b = metabotropic
both activated by GABA
what are neuromodulators
dopamine
serotonin
Norepinephrine
neuropeptides like endorphins
interact mainly or entirely with metabotropic receptors
describe purpose of neuromodulators
not directly involved in fast flow of info, modulate global neural states like attention, mood, alertness
shapes overall properties (global) of neuron systems
overall functional states of nervous system
describe effects of norepinephrine
involves in sleep wake cycles and attention
when asleep = neurons that release norepi are off
when awake = neurons that release norepi fire at steady rate
if suddenly pay attention = fires bursts of ap and release more norepi
describe effects of serotonin
given for depression
specific serotonin reuptake inhibitors = increases amount of serotonin in brain
correlation between serotonin and mood
more serotonin is better than not enough
describe effects of dopamine
involved in behaviour associated with reward
like casino and gambling, win = brain releases dopamine then neurons will release dopamine when gamble and you become a gambler
also cigarettes = cause increase in dopamine and indirectly affects other receptors, if an addict went into a room with people smoking = neuron will release dopamine
where do neurons that release neuromodulators originate
small brainstem or mid brain nuclei
axons project diffusely throughout the brain
describe neurons that release neuromodulators
small amount of neurons
small clusters of them
axons spread and branch all over brain and cerebral cortex
neurons that release neuromodulators are usually…
targets for pharmacological agents = treat psychological disorders
main targets for substance abuse
describe effect of cocaine
cocaine up nose = face turns numb
cocaine = local anesthetic like lidocaine and benzocaine
inhibits voltage gated sodium channels
but people still use it since it increases amount of dopamine and has stimulant and reinforcing effects, makes ppl wanna do it again
name the 2 specific areas where neurons that release neuromodulators are
SN = substantial nigra
VTA = ventral tegmental area
describe effects of antidepressants
affect serotonin transmission
describe effects of amphetamines and cocaine and other stimulants
affect dopamine and norepinephrine (speeds you up, causes norepi neurons to release a lot of it) transmission
