lecture 3- communication at the synapse 1

Question 1

what is the action potential
-signal process- what happens to the cell?

Answer 1

-signal sent within the cell
-a rapid sequence of change in the voltage across a membrane

-when an action potential is sent, it depolarises the cell because positive ions come flooding into the cell causing the charge to become positive
-and that’s the signal that’s sent along the length of the axon

Question 2

resting cell has a ______ charge

Answer 2

negative

Question 3

-what is the synaptic cleft
-what is presynaptic neuron
-what is post synaptic neuron

Answer 3

-gap between neurons (20-30nm) between membranes of cell
-presynaptic neuron : neuron that sends signal
-postsynaptic neuron: receives the signal

Question 4

types of signalling, communication between neurons

Answer 4

-electrical
-chemical (involves neurotransmitters)

Question 5

electrical signalling
-synapses
-how does it work

Answer 5

-electrical synapses : pre and post synapse are linked at a gap junction

-between the two membranes at gap there are tiny little channels that are constantly open and allow space for the fluid in the presynaptic cell to flow into post synaptic cell
-direct, passive flow from one neuron to another

-ions diffuse through channels continuing the action potential

Question 6

electrical signalling is incredibly ___
-what do the graphs in lecture show

Answer 6

-fast
-the post synaptic neuron can start to signal within ms of receiving input from the pre synaptic neuron
-

Question 7

what animal was the electrical synapse first discovered in

Answer 7

-humble crayfish
-has many electrical synapses in the circuit which allows it to initiate escape from predators

Question 8

electrical synapses allows for ______ of signals

Answer 8

-synchronisation

-we have them in our brainstem - brainstem neurons regulate breathing
-also have them in the system that secretes hormones into bloodstream
-action potential fire at practically the same time-achieves one big result

Question 9

chemical signalling
-chemical synapses
-neurotransmitters

Answer 9

-chemical synapses- no link between neurons

-neurotransmitters are released from the presynaptic cell (eg dopamine, serotonin)
-molecules diffuses across that gap and bind to receptors on the post synaptic cell membrane
(receptors are specific to the neurotransmitters)

-neurotransmitter either excites or inhibits the neuron that receives it

Question 10

what does a neurotransmitter do to a neuron when it binds to receptors on the post synaptic cell

Answer 10

-neurotransmitters either excites or inhibits the neuron that receives it.
-increase / decrease the likelihood of the receiving neuron producing its own action potential

Question 11

electrical vs chemical signalling
-frequency
-connection
-transmission speed
-method of communication
-direction of communication

Answer 11

electrical / chemical
-less common/ more common
-small gap junction/large synaptic cleft
-fast transmission / slow transmission
-direct electrical coupling/opening of ion channels
-bidirectional/more commonly unidirectional

Question 12

chemical signalling
steps

Answer 12

1-transmitter synthesised and stored in vescicle

2-action potential invades presynaptic terminal

3-depolarisation of presynaptic terminal causes opening of voltage gated ca channels

-4-influx of ca2 through channel

5-cas causes vescicles to fuse with presynaptic membrane

6-transmitter released into synaptic cleft via exocytosis

7-transmitter binds to receptor molecules in the postsynaptic membrane

8-opening or closing of post synaptic channels

9-postsynaptic current causes excitatory or inhibitory postsynaptic potential that changes the excitability of the post synaptic cell

10-removal of neurotransmitters by glial uptake or enxymatic degradation

11-retrieval of vesicular membrane from plasma membrane

Question 13

chemical signalling key steps

Answer 13

• 1-6 : synthesis , storage and release of neurotransmitters (NT’s)

-7: binding of NTs to post synaptic receptors
-8-9 changes in post synaptic cell

10-11 : deactivation of NT’s to end the signalling

Question 14

explain

-criteria for substance being a neurotransmitter

-synthesis, storage and release of neurotransmitters

Answer 14

-a substance is a NT if
-its present in the pre synaptic terminal , stored in a vesicle
-its released in response to an action potential arriving at the terminal
-there are receptors on the post-synaptic cell it can bind to

(there are neurotransmitters that break these rules)

Question 15

two categories of neurotransmitters, differences between them
-howthey respond to stimulation

Answer 15

-small molecule neurotransmitters
-neuropeptides

-small molecule vesicle are smaller ,neuropeptide vesicles are larger, pick up staining

-stored differently in the cell
small molecule
-cell body enzymes are needed for task, enzymes synthesised
-axon-enzymes are transported
-terminal-NT synthesised and packaged into vesicles

neuropeptides:
-cell body: enzymes synthesised and packaged into vesicles with NT precursors
axon-vesicles transported
terminal: NT’s synthesised inside the vesicle

-how they respond to stimulation
-low frequency signalling arriving at the end of the cell, it doesn’t stimulate the cell very much, will only be localised increase in ca2+, only the small molecule neurotransmitters will be released
-high frequency stimuli will cause a more distributed release of ca2+
-both types of transmitter will be released

Question 16

release of NT’s

Answer 16

-triggered by arrival of the action potential at the presynaptic terminal
(influx of ca2+ ions)
-vesicles packages then merge with the synapse membrane and then contents are then released into synaptic cleft (from vesicles)
(called exocytosis)

Question 17

binding to receptors stage
-ionotropic receptors (protein ion channel)

Answer 17

ionotropic receptors
-neurotransmitter is specific to receptor ion channel
-neurotransmitter binds to ion channel and channel structure changes - it opens (it does not enter the post synaptic cell)
-the channel opens
-ions flow across into the post synaptic cell
-the action potential is triggered in the post synaptic cell

Question 18

binding to receptors
metabotropic receptors

Answer 18

-the neurotransmitter binds to a receptor protein
-the receptor activates the attached G proteins
-the G protein detaches and can dock onto an effector protein
-the effector protein triggers the opening of an ion channel , and ions flow into post synaptic cell
-alternatively the g protein docks on the ion channel directly

-this process involves more signalling
-slower than ionotropic receptors

Question 19

changes in the post synaptic cell

Answer 19

-cells receive multiple inputs from neighbouring neurons
-excitatory or inhibitory
-influences are summed to determine if signals are sent

Question 20

excitatory and inhibitory neurons
-threshold
example

Answer 20

if only one neuron fires in this cell , get a little increase in positive charge but not enough to reach the threshold
-(critical threshold required for the charge)
-if two inputs are summed together thats enough for signal to be sent

Question 21

-inhibitory signal makes things more ______.

Answer 21

negative,
so reduces the chances any signal can be sent, since the charge is lower than resting model

Question 22

neurotransmitter deactivation

Answer 22

-neurotransmitter detaches from the receptor and its then
-transported back into the pre synaptic neuron (reuptake )
or
-broken down by enzymes in the synaptic cleft
-by products of this breakdown may be recycled

Question 23

how do psychoactive drugs work
-drugs can influence all the stages of _________ production

Answer 23

-psychoactive drugs interact with neurotransmitter systems
-neurotransmitter

Question 24

two types of drugs

Answer 24

-agonists : mimic or enhance the effects of a naturally occurring neurotransmitter

-antagonists : block or reduce the effects of a naturally occurring neurotransmitter

Question 25

agonists
-synthesis
-release
-binding
-deactivation

Answer 25

synthesis
-agonist will increase the amount of nt made
-destroys enzymes that break down NTs

release :
-agonists increase the amount of NT’s released by cleft
-block autoreceptors which limits NT release

binding
-direct agonist:substance which is similar enough to a particular neurotransmitter that it can bind to the normal neurotransmitter site and still cause those changes , cause channel to open

deactivation: destroys enzymes that break down NTs
-block reuptake ports for taking NTs back into the cell

Question 26

antagonists
-synthesis
-release
-binding

Answer 26

synthesis
-decrease the amount of NT made
-breaks open vesicles so NTs are destroyed by enzymes

release
-antagonists block the release of NTs from cell
-activates autoreceptors, to limit NT release

binding: direct antagonists again have the right shape and so bind to receptor site blocking the NT

Question 27

what ionotropic receptor can aceytylcholine bind to
-what does this do, involved in what

Answer 27

-nicotine receptors
-ionotropic
-excites skeletal muscles (contractions)
-in CNS - involved in learning, memory, arousal and moto control and alertness after waking

Question 28

what metabotropic receptors do aceytlcholine bind to
-involved in what

Answer 28

-muscarinic receptors
-metabotropic ‘-found primarily in the CNS
-involved in control of physiological functions/ parasympathetic nervous system (eg salivation, lacrimation,digestion)
-slows heart rate , relaxes smooth muscles (i.e in the gut)

Question 29

acetylcholine receptor agonists
-nicotine
-at lower doses
-at higher doses

Answer 29

-nicotine acts as an agonist on the ionotropic receptors, enhancing the effect of ACh in the CNS
-At lower doses , it produces some feelings of euphoria and relaxation
-at high doses, it produces nausea, vomiting and mental confusion as it overstimulates those receptors in the cns

Question 30

acetylcholine receptor agonists
muscarine

Answer 30

-found in many mushrooms
-muscarine acts as an agonist on the metabotropic muscarine receptors
-enhances parasympathetic functions
-nausea, vomiting, increased salivation, slowed heart rate (bradycardia), reduced blood pressure
-can lead to circulatory collapse, coma and death

Question 31

acetylcholine receptor antagonists
-nicotinic receptor antagonists

Answer 31

-find alot of this in venom of creatures eg snakes
-a-bungarotoxin-the venom of the branded krait snake
-bond directly to the receptors at the neuromuscular junction
-irreversible blocking of nicotine ACh receptors
-prevents skeletal muscle activation leading to paralysis
others : curare, cobra a-neurotoxin, contoxins from marine cone snails

Question 32

acetylcholine receptor antagonists
-muscarinic receptor antagonists

Answer 32

found in things such as atropine (deadly nightshade) and scopolamine (Henbane)
-reduces parasympathetic functions
-may be used to increase heart rate (bradycardia treatment)
-used in surgery to reduce saliva production

Question 33

glutamate
what is it

Answer 33

-most important transmitter for normal brain function
-almost all excitatory neurons in the central nervous system are glutamatergic : (have receptors that respond to glutamate)
-over half of all brain synapses are thought to release glutamate
-glutamate does not cross the blood brain barrier , therefore must be synthesised from local precursors

Question 34

agonists of glutamate
ibotenic acid

Answer 34

ibotenic acid
-prolongs activation of the NMDA receptor(ionotropic) (key receptor of glutamate)

-NMDA : linked to long term changes in the brain (‘synaptic plasticity’) necessary for learning and memory
-extended function leads to cell damage and death (excitotoxicity)

Question 35

antagonists of glutamate
ketamine

Answer 35

ketamine : antagonist of the NMDA receptor
-blocks the excitatory effect of glutamate
-used as a sedative and anaesthetic
-has distancing effect on perception , recreationally used for hallucinatory properties

Question 36

glutamate and excitotoxicity (Olney ,1969)

Answer 36

-glutamate agonists can cause excitotoxicity - cell death due to enhanced activation
-excitotoxicity also occurs following cell damage due to injury or stroke
damage : releases glutamate: glutamate activates post synaptic cells : cells die

Question 37

if an excess of glutamate is causing damage to the cells , it could be possible to use ________ _______ to treat stroke or brain damage

Answer 37

glutamate blockers
-glutamate antagonists would block the receptors , limiting the damage caused by the excess glutamate (neuroprotective therapy)

this may not work as its difficult for specificity , we have many glutamate receptors widespread in the brain ,so if you give someone an antagonist its not just going to affect someone in the brain region of injury its going to affect other regions too- so other glutamate receptors are blocked and signalling reduced or lost

Question 38

f an excess of glutamate is causing damage to the cells , it could be possible to use glutamate blockers to treat stroke or brain damage

why might this not work?

Answer 38

this may not work as its difficult for specificity , we have many glutamate receptors widespread in the brain ,so if you give someone an antagonist its not just going to affect someone in the brain region of injury its going to affect other regions too- so other glutamate receptors are blocked and signalling reduced or lost

a second reason this may not work is due to timing
-glutamate increase after brain injury has been studied , and there is a really sharp increase in the level of glutamate right after injury (10.30 mins in rats , uncertain in humans)
-but if you keep measuring the glutamate , there’s a second sustained, milder increase days or weeks after injury

Question 39

-glutamate spikes after brain injury, then again there’s a milder increase
why
ikonomidou and turski (2002)

Answer 39

-glutamates normal physiological role is to promote neuronal survival
-so initial increase directly after injury - links s to cell death
-but the second later increase may be the bodys attempt to repair and bring back glutamates role of developing synaptic connections, help mainatin cell function
-so if you give the antagonist too late youll miss out on blocking the cell death and end up blocking this process