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physiology > Lectures 9-16: Anatomy and Physiology of Synapse + Synaptic Physiology & Integration > Flashcards

Lectures 9-16: Anatomy and Physiology of Synapse + Synaptic Physiology & Integration Flashcards

1
Q

Electrical synapses…

A

Gap junctions (connexons)

Symmetrical bidirectional

very fast (Signals are conveyed cell to cell in <0.3ms)

Ca2+ independent

Temperature insensitive

Large synapse

Allow synchronisation between neighbouring neurones

Usually excitatory

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2
Q

Chemical synapses:

A

Highly developed structure

Polarised

Pre and post synaptic density

Slow (synaptic delay)

Ca2+ dependent

Temperature sensitive

Excitatory or inhibitory

Specific point to point activity

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3
Q

Molecule that is the main neurotransmitter In excitatory synapses…

A

Glutamate

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4
Q

Molecule that is the main neurotransmitter In inhibitory synapses…

A

GABA

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5
Q

The uptake and storage of dopamine in pre synaptic vesicles…

A

Allows high concentration of transmitter

Allows quantal release of transmitter

Is inhibited by reserpine

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6
Q

Arrival of an action potential at pre synaptic terminal firstly triggers…

A

Opening of voltage gated calcium channels

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7
Q

Botulinum toxins cause paralysis because they…

A

Proteolytically cleave SNARE proteins

Inhibit release of acetylcholine at neuromuscular junctions

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8
Q

Acetylcholine:

A

Binds to ionotropic receptors

Binds to metabotropic receptors

Mediates excitatory transmission in the brain and in the autonomic system

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9
Q

Glutamate:

A

Binds to ionotropic receptors

Binds to metabotropic receptors

It’s action is terminated by uptake into glial cells

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10
Q

Noradrenaline:

A

Binds to metabotropic receptors

Mediates excitatory transmission in the brain and in the autonomic system

Can be enzymatically inactivated in pre synaptic terminals

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11
Q

The gap between pre and post synaptic elements at a chemical synapse is about…

A

50nm

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12
Q

electrical synapses are in…

A

mammalian retina, spinal cord, bran regions

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13
Q

types of chemical synapse:

A

axo-dendrite

axo-somatic

axo-axonic

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14
Q

Axo-dendritic=

A

Between the axon of one Neurone and dendrite of another

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15
Q

Axo-somatic =

A

Between the axon of one neurone and the soma of another

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16
Q

Axo-axonic=

A

Between the axon of one neurone and the axon of another

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17
Q

Synapses can be ….

A

Gray’s type 1 = asymmetrical, excitatory

Gray’s type 2 =
symmetrical, inhibitory

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18
Q

Autonomic nervous system:

A

Controls voluntary function

Consists of sympathetic and parasympathetic

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19
Q

Sympathetic nervous system:

A

Fight/flight

Short myelinated preganglionic fibres

Long unmyelinated postganglionic fibres

Postganglionic neurones are noradrenergic = they release noradrenaline which acts on adrenoceptors

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20
Q

Parasympathetic nervous system:

A

Rest/digest

Long myelinated preganglionic fibres

Short unmyelinated postganglionic fibres

Postganglionic neurones are cholinergic = they release acetylcholine which acts on muscarinic acetylcholine receptors

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21
Q

All preganglionic neurones are …

A

cholinergic - use acetylcholine as neurotransmitter and act on nicotinic acetylcholine receptors

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22
Q

Nicotinic acetylcholine receptors are…

A

Ligand gated ion channels

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23
Q

Muscarinic acetylcholine receptors are…

A

G protein coupled receptors

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24
Q

Stages of chemical synaptic transmission:

A

1) Neurotransmitter synthesis
2) Neurotransmitter storage into synaptic vesicles
3) Synaptic vesicle cycling, exocytosis and transmitter release
4) transmitter binds to receptor whose identity determines post synaptic response
5) removal of neurotransmitter from synaptic cleft

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25
Q

Vesicles:

A

Vesicles protect transmitters from degradation by cytoplasmic enzymes and allow regulation

Most transmitters are in 40-50nm vesicles

Neuropeptides (e.g somatostatin) are in larger >100nm dense core vesicles

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26
Q

Vesicle cycling and exocytosis:

A

Vesicles in the reserve pool are primed to enter readily-releasable pool

Primed vesicles can be induced to fuse with the plasma membrane by sustained depolarisation (elevated Ca2+ in cytoplasm)

Snare zipping is triggered by Ca2+ entering via VOOC

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27
Q

Synaptotagmin =

A

Is a calcium sensor, it regulates SNARE zipping

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28
Q

SNARE zipping

A

bridges lipid bilayers and plasma membranes bringing them in proximity and inducing their fusion

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29
Q

Botulinum toxins=

A

Inhibit vesicle fusion and transmitter release

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30
Q

Quanta -

A

Corresponds to release of individual synaptic vesicles at the neuromuscular junction

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31
Q

Excitatory post synaptic potential:

A

Depolarisation

Inward current (Na2, Ca2+)

Increased firing rate (graph increases)

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32
Q

Inhibitory post synaptic potential:

A

Hyperpolerisation

Inward (Cl-) or outward (k+)

Decreased firing rate (decreased graph)

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33
Q

Amino acid transmitters -

A

Mediate excitatory (e.g.glutamate) or inhibitory (e.g.GABA or glycine) transmission via ionotropic receptors

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34
Q

Catecholamine and peptide (e.g. enkephalins) transmitters -

A

modulate transmission via metabotropic receptors by altering the probability of release (of glutamate, GABA, acetylcholine) from presynaptic axon terminals

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35
Q

Acetylcholine -

A

Mediates excitatory transmission via ionotropic receptors

modulates transmission via metabotropic receptors

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36
Q

Purpose of chemical synapses:

A

Information transfer between pre synaptic and post synaptic cells

Amplification of signals

Integration of multiple inputs

Plasticity - learning and memory

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37
Q

Neurones are highly complex:

A

Can generate intrinsic activity or receive inputs from other neurones via synapses

Integrate received synaptic inputs

Encode patterns of activity for output

Distribute outputs to other Nero s via synapses

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38
Q

Ionotropic transmitters:

A

Open and close to allow ions through a channel by ligand inducing conformational change

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39
Q

Metabotropic transmitters:

A

Linked to G protein which is activated when ligand binds to receptor which activates a secondary messenger

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40
Q

What makes transmitter excitatory?

A

If transmitter opens Na+ or Ca2+ ion channels
- these enter cell because of electrochemical gradient
= membrane potential becomes less negative
=excitatory postsynaptic potential

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41
Q

What makes transmitter inhibitory?

A

If transmitter opens k+ channels
- k+ exits cell down electrochemical gradient
=membrane potential becomes more negative
=inhibitory postsynaptic potential

If transmitter opens Cl- channels
- Cl- enters cell down electrochemical gradient
=membrane potential becomes more negative
=inhibitory postsynaptic potential

42
Q

if equilibrium potential of chloride (Ecl) is less than resting membrane potential (Vm) …

A

net influx of Cl- ions = hyperpolarisation = inhibitory

in adult

43
Q

if equilibrium potential of chloride (Ecl) is more than resting membrane potential (Vm) …

A

net efflux of Cl- ions = depolarisation = excitatory

in young

44
Q

calcium channels…

A

can be both inhibitory and excitatory

adult = inhibitory
young = excitatory
45
Q

excitatory neurotransmitter:

A

depolarises excitatory post synaptic potential

requires increase in intracellular positive charge (Na or Ca)

= cation influx causes depolarisation

46
Q

inhibitory neurotransmitter:

A

hyperpolarises inhibitory post synaptic potential

requires decrease in intracellular positive charge (Na or Ca)

= cation efflux or anion influx causes hyperpolarisation

47
Q

cys-loop receptor superfamily:

A 
has both inhibitory and excitatory receptors 
nACH = excitatory
5-HT3 = excitatory 
GABAa = inhibitory
glycine = inhibitory
  • have common molecular structure
48
Q

mutated glycine receptors..

A

are cation selective

49
Q

mutated Ach receptors..

A

are anion selective

50
Q

comparison of excitatory post synaptic potential and action potential;

A

both caused by Na influx…
- excitatory post synaptic potential at ligand gated
cation channel
- action potential at voltage gated sodium channels

excitatory post synaptic potential are smaller than action potentials…

  • lower number of synaptic ligand gated cation channels than axonal voltage gated sodium channels
  • differences in biophysical properties between these two channels
51
Q

voltage vs ligand gated :

A 
vlotage = hogh cation selctivity = reversal potential is close to reversal potential for the ligand
ligand = less selective between different types of cation = reversal potential is around zero - only slightly more selective for one ion
52
Q

Spatial synaptic integration =

A

The integration of inputs that arrive on a dendrite of a neurone at multiple different places at the same time

All cause a small depolarisation that summate to produce a larger effect

Total effect on soma membrane potential is sum of all synaptic potentials

E.g purkinje cells

53
Q

Temporal synaptic integration:

A

Integration of signals over time
Series of action potentials arriving and active synapse repeatedly = summation of effects over time

Requires long time constant of excitatory post synaptic potential = post synaptic potentials add up

54
Q

Why does length constant affect spatial synaptic integration?

A

Amplitude of synaptic potential change reduces with distance from synapse

Decline in synaptic amplitude with distance from synapse is determined by length constant

55
Q

Length constant =

A

Distance taken for excitatory post synaptic potential has declined to 37% of its maximum

56
Q

What parameters determine the length constant of a dendrite?

A

Dendritic membrane resistance

Axial resistance of dendrite

Not affected by Myelination as dendrites are not myelinated

57
Q

What parameter

Influences the time constant of a dendrite?

A

Dendritic Membrane capacitance

58
Q

When working out Vm, You cannot combine effects of synapses from different distances because…

A

Activity at one synapse opens ion channels
= change in membrane resistance
= change in length constant
= change in effect on cell soma potential from other synapses

59
Q

Time constant =

A

Time it takes for excitatory post synaptic potential to declined to 37% of its maximum

= membrane resistance x membrane capacitance

60
Q

Effect of greater membrane resistance:

A

Synaptic current doesn’t leak as rapidly

Postsynaptic potential lasts longer

= longer time constant

61
Q

Effect of greater membrane capacitance:

A

More charge resulting from synaptic current flow is stored and discharged after the synaptic current flow has stopped

Postsynaptic potential last longer

=longer time constant

62
Q

Temporal integrator:

A

Long time constant

Majority of excitatory postsynaptic potential contribute to activation of action potentials

Precise timing of action potentials is only weakly linked to input pattern

E.g. oculomotor integrator (eye position)

63
Q

Coincidence detector:

A

Short time constant

Only few excitatory postsynaptic potentials contribute directly yo activation of action potentials

Timing of action potentials is closely linked to coincident synaptic inputs

E.g. sound localisation between left and right ear and visual processing

64
Q

Silent postsynaptic inhibition:

A

Occurs when synaptic reversal potential equals the resting membrane potential
= no current flow

65
Q

if reversal potential is more positive than membrane potential…

A
  • net inflow of positive charge

- depolarization of the postsynaptic membrane potential

66
Q

if reversal potential is more negative than membrane potential…

A
  • net outflow of positive charge

- hyperpolarisation of the postsynaptic membrane potential

67
Q

length constant affects..

A

spatial summation

68
Q

time constant affects…

A

temporal summation

69
Q

synaptic integration is important because…

A

neurons receive multiple synaptic inputs and provide multiple synaptic outputs

enables info processing in CNS

integration of synaptic inputs determines nervous system function

70
Q

parameters that effect synaptic integration:

A
  • complexity of neuritic processes
  • distance of synapse to soma
  • relative position of synapses to each other
  • amplitude of current flow at synapse (multiple synaptic inputs are required to depolarize neuron sufficiently to trigger action potential)
  • length constant affects spatial summation
  • time constant affects temporal summation
71
Q

if excitatory and inhibitory synapses are on different dendrites at some distance from soma…

A

…results in linear summation of currents in soma - smaller depolarization

72
Q

if inhibitory synapse between excitatory synapse and soma on same dendrite…

A

…results in current flow that counteracts current flow initiated at excitatory synapse

…results in opening of ion channels lower membrane resistance

  • changes length constant of dendrite
  • affects spread of EPSP

= both result in non linear summation

= cannot combine effects on soma of EPSP and IPSP

73
Q

short time constant…

A

neuron will act as coincidence detector

only EPSPs that arrive nearly simultaneously will summate

74
Q

long time constant…

A

Neuron will integrate/summate EPSPs over longer period

precise timing of EPSPs is less important

neuronal activity is more determined by average rate of EPSPs

75
Q

What happens if synaptic reversal potential equals the resting membrane potential?

A

= silent postsynaptic inhibition

  • neurotransmitter binds to receptor
  • opening of postsynaptic ion channels
  • change in membrane resistance, but no current flow and no change in membrane potential
76
Q

when there is only an inhibitory input…

A

just activates inhibitory synapse

= no current flow

77
Q

when there is only excitatory input…

A

more positive than resting potential, ion move into cell

= depolarisaton

78
Q

when there is excitatory and inhibitory input…

A

some leakage = less membrane resistance = change in membrane resistance is smaller
= inhibitory ‘shunt’
…(the depolarising current is balanced by the inhibitory current, removing the depolarising effect of the EPSP)

79
Q

“Silent” Postsynaptic Inhibition in the CNS…

A

GABA is main inhibitory neuotransmitter in CNS

GABAa receptor = ligand gated chloride channel

GABAb receptor is a (metabotropic) GPCR

chloride reversal potential is -70mV

80
Q

problems associated with studying integration..

A

connected neurons frequently form multiple contacts with each other
= even stimulating a single neuron usually activates multiple synaptic sites

81
Q

experimental approaches for studying integration…

A

computational models

  • useful
  • only as good as underlying assumptions

photolysis of caged neurotransmitter to mimics synaptic transmitter release
(photo release of caged glutamate to simulate effect of glutamate release at individual synapses

82
Q

photolysis of caged neurotransmitter:

A
  1. brain slice is bathed in solution of ‘caged’ neurotransmitter (inactive)
  2. exposure to UV light releases active transmitter – mimics synaptic release
  3. neuron is filled with fluorescent dye to visualise processes
  4. UV light is focussed on small spots along dendrites and briefly turned on = release of small amount of glutamate
83
Q

EPSP and IPSP summate, but summation is only linear when…

A

…when synapses are on different dendrites so that changes in membrane resistance do not affect spread of EPSP or IPSP

84
Q

“Silent” postsynaptic inhibition:

A

Inhibitory synapses can affect EPSPs, even if they do not cause a change in membrane potential

85
Q

Homosynaptic short-term synaptic plasticity:

A

amplitude of synaptic potentials/synaptic currents can vary strongly depending on preceding activity
= activity dependent short-term plasticity

86
Q

synaptic facilitation -

A

‘paired-pulse’ facilitation:

  1. first action potential
    - Ca2+ influx = release of transmitter from some vesicles = priming of other vesicles
  2. increased number of primed vesicles
  3. second action potential
    - Ca2+ influx = more transmitter release
87
Q

synaptotagmin 7 =

A

= calcium sensors that control synaptic vesicle release, essential for synaptic facilitation

88
Q

spike broadening during synaptic facilitation:

A

repetitive firing can lead to spike broadening

  • longer presynaptic depolarisation
  • more presynaptic Ca++ influx
  • more transmitter release
  • increased synaptic response
89
Q

synaptic depression:

A

at some synapses repeated firing of presynaptic neuron leads to progressively weaker postsynaptic responses

  1. first action potential
    - Ca2+ influx, releae of docked vesicles
  2. causes depletion of docked vesicles
  3. second action potential
    - Ca2+ influx, few docked vesicles ready to release
90
Q

Heterosynaptic modulation of synapse function…

Postsynaptic modulation:

A

Modulatory input alters sensitivity of postsynaptic membrane to presynaptic transmitter release

91
Q

Heterosynaptic modulation of synapse function…

Presynaptic modulation:

A

Modulatory input alters presynaptic transmitter release

Two examples:

  • Presynaptic inhibition
  • Presynaptic facilitation
92
Q

Postsynaptic modulation – Example 1 : GABAa receptor modulation by phosphorylation

A
  • activation of G-protein coupled receptor (e.g. serotonin receptor)
  • activation of protein kinase (e.g. protein kinase A)
  • phosphorylation of GABAA receptor
  • alters GABAA receptor function – can either enhance or suppress receptor function depending on phosphorylation site and subunit composition of GABAA receptor
93
Q

Postsynaptic modulation – Example 2 : Altering the number of postsynaptic receptors

A
  • GABAA receptors are assembled in endoplasmatic reticulum and packaged into vesicles in Golgi apparatus
  • Insulin promotes the insertion of GABAA receptors into the postsynaptic membrane = increase in postsynaptic receptor number
  • BNDF (brain-derived neurotrophic factor) promotes removal of GABAA receptors = decrease in postsynaptic receptor number
94
Q

Presynaptic inhibition – a presynaptic mechanism of heterosynaptic modulation

A

Inhibitory + Excitatory Input

= Reduced presynaptic Ca++ influx

= Reduced transmitter release

= Reduced receptor activation

= Reduced EPSP

95
Q

Heterosynaptic facilitation – a presynaptic mechanism for synapse strengthening

A

Example: Sensitisation of gill withdrawal reflex in sea hare Aplysia californica

  • Touch of siphon alone produces weak gill withdrawal response
  • Touch of siphon briefly after electrical shock of tail enhances gill withdrawal response, i.e. touch response has been sensitised
  • Sensitisation is due to heterosynaptic facilitation of sensory to motoneuron synapse
96
Q

Heterosynaptic facilitation –How does it work?

A

1) 5-HT activates metabotropic 5-HT receptor
2) 5-HT receptor activates adenylate cyclase
3) Increase in intracellular cAMP concentration
4) cAMP activates protein kinase A
5) PKA phosphorylates voltage-gated K+ channel = reduction in K+ current during action potential = broadening of AP
6) Voltage-gated Ca++ channels are open longer = more Ca++ influx
7) Higher Ca++ concentration = more transmitter release

97
Q

Mechanisms of synaptic modulation:

A

Presynaptic:

  • altered vesicle release
  • altered Ca++ entry
  • altered vesicle recycling

Postsynaptic:

  • altered receptor function
  • altered receptor number
98
Q

long term synaptic plasticity

A
  • long term potentiation in hippocampus is important for learning
99
Q

Synapses with low release probability….

A

are more likely to show synaptic facilitation

100
Q

synapses with high release probability….

A

more likely to show synaptic depression

101
Q

Heterosynaptic modulation of synapse function:

A
  • Altering sensitivity of postsynaptic neuron to presynaptic transmitter release – can lead to facilitation or depression of synapse
  • Altering presynaptic transmitter release by modulation of presynaptic calcium influx – can lead to facilitation or depression of synapse
102
Q

short term synaptic plasticity:

A
  • Synaptic facilitation

- Synaptic depression

physiology (8 decks)

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