Synapses and the Role of Neurotransmitters Flashcards

1
Q

what does the CNS consist of?

A

brain and spinal cord

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2
Q

what are the different roles of the PNS?

A

sensory nervous system
motor systems
autonomic nervous system
- sympathetic
- parasympathetic
- enteric

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3
Q

what specialisations do neurones possess in order to communicate?

A

dendrites (form the dendritic tree) - receiving input from other neurones
axon hillock - (junction of the axon from the cell body) AP generation
axon - impulse conduction
axon terminal (or synaptic bouton) - release of neurotransmitter triggered by AP

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4
Q

at a sensory neurone, where is the AP generated?

A

not all AP are generated at the axon hillock
in sensory neurones its at the nerve endings

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5
Q

what are synapses?

A

site of communication between two neurones, two cells or a cell (muscle cell) and a neurone

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6
Q

what are the 2 different types of synapses?

A

electrical
chemical

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7
Q

what is the electrical synapse?

A

known as ‘gap junction’
fastest and most primitive
between adjacent cells or neurites
direct transfer of ionic current (also small molecules)
bi-directional

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8
Q

what is the structure of an electrical synapse?

A

connexons (protein) line up physically connecting the two cells by having half of each connexon in either cell.
there is a pore in the connexon allowing the passage of ions
information (ions) can travel in both directions - allows synchronous activity between cells

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9
Q

what is the difference between electrical and chemical synapses

A

electrical allows bi-directional transfer of info
chemical is uni-directional- transfer of information from pre-synaptic –> post synaptic cell

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10
Q

what does the electrical synapse do?

A
  • allows synchronous activity
  • relatively rare between neurones in the CNS, although important in development
  • glia-neurone, glia-glia communication - much more common than neurone-neurone
  • also, cardiac myocytes are connected via gap junctions - allows cardiac muscle to depolarise to cause contraction
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11
Q

what is the chemical synapse?

A
  • close association between the presynaptic (axon terminal) and the postsynaptic membrane
  • presynaptic terminal releases neurotransmitter
  • diffuses across the synaptic cleft
  • interacts with receptor on the postsynaptic membrane
  • plenty of vesicles to allow for the transport of the neurotransmitter.
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12
Q

what is the synaptic cleft?

A

space that separates two neurones

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13
Q

explain the critical process of neurotransmission

A
  1. Action potential (initiated in the cell body) propagates down the axon, invading the nerve terminal (The AP is dependent on membrane depolarisation which is dependent on the influx of Na+ through voltage-gated Na+ channels)
  2. Depolarisation at the nerve terminal triggers a conformation change in Ca2+ voltage gated ion channels causing them to open
  3. Ca2+ influx into the nerve terminal triggers the release of neurotransmitter
  4. Vesicle will move and fuse with the membrane of the presynaptic terminal -this portion is called the active zone
  5. Docks with the membrane and the vesicle contents (neurotransmitter) are released into the synaptic cleft via exocytosis
  6. Neurotransmitter diffuses across the synaptic cleft (down its concentration gradient)
  7. Neurotransmitter then binds to the receptor on the post synaptic membrane. (The receptor is very specific so only one type of neurotransmitter will bind to it)
  8. A signal is communicated and this causes depolarisation - EPSP in post synaptic neurone –> lead to AP.
  9. Signal must be quickly terminated after the signal is processed. The mechanism to do this, depends upon:
    - the synapse itself and what neuron is involved
    - the neurotransmitter released
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14
Q

explain the 1st mechanism used to terminate a signal in the synapse

A

Mechanism 1: The neurotransmitter is taken back up into the nerve terminal by a specific re-uptake mechanism. This is done rapidly:
1. Protein on the cell surface membrane (re-uptake sites) transport neurotransmitter back in pre-synaptic terminal.
2. Once the neurotransmitter is taken up, it can be broken down by enzymes present in the presynaptic membrane. Many (not all) of the enzymes which break down the neurotransmitter are expressed via the mitochondria
3. However, it can also be re-packaged into vesicles

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15
Q

explain the 2nd mechanism used to terminate a signal at the synapse

A

Mechanism 2:
Here mitochondria are in the extracellular fluid.
1. Enzymatic activity in the extracellular fluid breaks down the neurotransmitter released in the synaptic cleft without reuptake
2. This mechanism is used to terminate signalling at certain synapses e.g. those that use acetylcholine

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16
Q

define neurotransmitters

A

chemical messengers at the synapse

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17
Q

what are the 4 major neurotransmitters?

A

Acetylcholine (ACh)
Amino acids
Monoamines
Neuroactive peptides

18
Q

what are the different AA neurotransmitters? (all start with G)

A

glutamate (most abundant excitatory NT in the CNS) - does most of the brain activity involving stimulation
GABA: (gamma aminobutyric acid) most abundant inhibitory NT
Glycine

19
Q

name a few monoamines

A

noradrenaline
dopamine
Serotonin (5-hydroxytryptamine - 5-HT)

20
Q

what are examples of neuroactive peptides?

A

More than 100 different kinds
e.g. opioid peptides (endorphin, enkephalin) tachykinins (Substance P, neurokinin A)

21
Q

what is the role of receptors in the synapse

A
  • Recognition site for a neurotransmitter
  • Its a membrane spanning protein expressed by the cell membrane on the post synaptic neuron
  • Its binding site stick out into extracellular compartment whilst the intracellular domain is related to signalling cascades
22
Q

how do the receptors transmit info across the synapse?

A

it initiates an intracellular signal (depolarisation) via changing its conformation
Receptors are specific for a single neurotransmitter - a neurotransmitter can bind to many different receptors whereas one receptor can only have one specific neurotransmitter binding to it i.e. one neurotransmitter - several receptor subtypes

23
Q

what can some exogenous substances do to receptors?

A

Man-made material and plant based material (exogenous substances) can also mimic molecules and bind to receptor sites

24
Q

what are the 2 types of receptor signalling mechanisms at the synapse?

A

Ionotropic
Metabotropic

25
Q

what is an ionotropic receptor mechanism?

A

receptor operated/ ligand gated ion channels
neurotransmitter binding induces conformational change –> specific channel opening –> ion movement
fast transmission

26
Q

what is an example of an excitatory ionotropic receptor?

A

glutamate AMPA, NMDA, kainate receptor subtypes
ACh nicotinic receptor subtype

27
Q

how does an inotropic receptor behave at an excitatory synapse?

A

1) An excitatory neurotransmitter binds to the receptor
2) This causes a conformational change in the Na+ ion channels causing it to open
3) This allows influx of Na+ (due to ionic driving force) causing depolarisation
4) This causes small excitatory post synaptic event (see in the graph) (EPSP - excitatory post synaptic potential)
5) This doesn’t last long as the Na+ is pumped out after
5) So excitatory neurotransmitters cause excitation in the post synaptic neuron

28
Q

what is an example of an inhibitory ionotropic receptor?

A

GABA a receptor subtype
glycine receptor

29
Q

how does an inotropic receptor behave at an inhibitory synapse?

A

1) An inhibitory neurotransmitter is released and interacts with a specific receptor
2) This causes conformation change in Cl- ion channel –> opens
3) This causes an influx of Cl-ions into the cell
4) The movement of Cl-is due to its concentration gradient (against electrical attraction)
5) This causes membrane hyperpolarisation
6) The membrane potential becomes more negative than the resting membrane potential = small inhibitory post synaptic potential (IPSP)

30
Q

what is a metabotropic receptor mechanism?

A

G -protein coupled Receptor
slower transmission - due to more steps
longer lasting effects on neurones excitability

31
Q

how does the metabotropic receptor mechanism work?

A

1) Conformational change in the receptor protein itself
2) This activates a G-protein – this is tethered (connected to) on the intracellular side of the membrane
3) The G protein then activates ‘effector systems’ - this can be excitatory or inhibitory depending on the particular receptor and G-protein
4) Slower transmission but longer lasting effects on the excitability of the post synaptic cell

32
Q

what is an example of a metabotropic receptor?

A

ACh muscarinic
GABA b
monoamine receptors (except 5-HT3)

33
Q

what are the 2 ways in which an activated G protein can affect different potential effector systems?

A
  1. open or close G-protein gated ion channels which allows for less/more ion movement changing the excitability of the cell
  2. stimulate or inhibit enzymes/ secondary messenger systems which can switch on/off an enzyme cascade E.g. ACh muscarinic receptors; GABAB receptors; monoamine receptors (except 5-HT3)
34
Q

how does a neurotransmitter cause different effects on the same cell?

A

One neurotransmitter can bind to multiple subtypes of receptors which can be either Ionotropic/Metabotropic
so a neurotransmitter can cause different effects on the same cell at the same synapse if multiple types of receptors are expressed at that synapse.
can have fast and slow transmission by same neurotransmitter

35
Q

why is synaptic integration of info important?

A
  • Each neuron has thousands of synaptic contacts on it, which all control the excitability of this one neurone.
  • Therefore, a single cell must integrate all of this information and decide what to do.
  • A neurone has inputs coming in along its entire surface area
36
Q

what are the 2 types of summation?

A

spatial
temporal

37
Q

what is spatial summation?

A

summing of post synaptic potentials generated at separate synapses

38
Q

how does spatial summation allow threshold to be reached?

A
  1. One small EPSP is not enough for the threshold value to be reached.
  2. Multiple simultaneous inputs from several synapses will cause the membrane potential to reach the threshold value (causing VG Na+ ion channels to open –> Na+ influx) resulting in the generation of an AP.
  3. An input closer to the axon hillock will have a much larger effect on the excitability of the cell compared an input on the dendritic tree.
39
Q

how is threshold reached at a mixed synapse (both excitatory and inhibitory neurotransmitters)?

A
  1. At a mixed synapse you can have both inhibitory and excitatory sypatic imputs
  2. An excitatory and inhibitory input, coming in at the same time can lead to no change at all for the excitability of the cell - membrane level of polarisation remains the same.
  3. If the level of the excitatory input = level of the inhibitory input, then they cancel each other out.
40
Q

what is temporal summation?

A

Summation over time
Single synapse repeatedly stimulating/ firing the cell (with a small gap in between)

41
Q

how does temporal summation work?

A
  1. one EPSP is quickly followed by another, so they can sum up because each one does not have time to decay away before another adds on top
  2. This can result in the threshold value being reached and an action potential being generated
  3. If EPSP are too slow, the first one will decay away!