Krueger 1 Flashcards

1
Q

what are synapses?

A

specialized zone of contact at which one neuron communicated with another

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

how many neurons in human brain?
avg human received how many synapses?
number of synapse in human brain?

A

neurons= 10^11 - 10^12
1000 synapses in avg. neuron
synapses in human= 10^15 - 10^16

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

2 types of synapses & explain

A

1) electrical- junctions b/w neurons permitting direct, passive flow of electrical current

2) chemical- junctions between neurons that comminicate via secretion of neurotransmitters
- chemical agents released by presynaptic neuron produced secondary flow in postsynaptic neurons activating specific receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

neurotransmitters undergo similar cycle (4 steps)

A

1) synthesis and packaging into synaptic vesicles
2) release from presynaptic cell
3) binding to post synaptic receptors
4) rapid removal and/or degradation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

influx of ____ through voltage-gated channels triggers secretion of ______

A

CALCIUM triggers secretion of NEUROTRANSMITTERS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

rise in Ca concentration, causes what?

A
  • synaptic vesicle to fuse with presynaptic plasma membrane and release contents into space between pre and post synaptic cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

electrical synapses are ___ _______

A

gap junctions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

structure of gap junctions (electrical synapses)

A
  • plasma membrane closely apposed (3nm)

- precisely aligned, paired channels= connexons (made up of connexins)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

how do connexins form pore that connects cells (electrical synapse)

A
  • 6 presynaptic connexin align with 6 postsynaptic connexins to form pore between 2 cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

(electrical synapse) gap junctions consist of wht complexes, and they are formed by?

A
  • hexameric complexes

formed by connexons coming together (present in pre/post synaptic membranes)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

components/formation of gap junction (how much of each thing)

(electrical synapse)

A
Connexin (x6)
-->
connexon (hemichannel)- (x2)
-->
gap junction channel (x 10^2 - 10^3)
--> 
GAP JUNCTION
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

different connexin isoforms determine….?

electrical synapse

A

transmission properties of the electrical synapse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what diffuses through neuronal gap junctions (2)

electrical synapse

A
  • all ions (ex: K, Na, Ca, Cl)

- small molecular weight compounds (ex: 2nd messengers: cAMP, IP3)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

experiment: patch clamping pair of electrical coupled neurons

  • type of current injected (depol/hyper)
  • when see AP?
A

2 electrically connected neurons

  • inject depolarizing current and neuron fires AP
  • polarizes to threshold and see AP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what happens at post synaptic neuron (patch clamping experiment)

  • speed of Na
A
  • see depolarization in post synaptic
  • no AP
  • the gap junctions (small openings), only fraction of Na can make it across the junction into postsynaptic neuron, the depolarization would be much smaller than presynaptic neuron
  • very fast b/c ass soon as AP, theres Na flowing into cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

inverse experiment of patch clamping

A
  • inject hyper-polarizing current into presynaptic current

- positive charged ions will flow from other side, hyper-polarizing neuron

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is end plate current (patch clamp experiment)

  • direction current flowing, causing..?
A

macroscopic current resulting from summed opening of many ion channels

  • current flowing= inward, causes post synaptic membrane potential to depolarize
  • depolarizing change inpotential, triggers postsynaptic AP by opening voltage-gated Na and K channels
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

directionality of electrical synapses transmission

- what does it depend on?

A

bidirectional

  • electrical synapses are rectifying due to voltage-dependent of gap junction channel opening
  • current can flow in either direction across gap junction, depending on which member of coupled pairs is invaded by AP
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

velocity of electrical synapse transmission

A
  • rapid
  • synaptic latency in order of 1ms
  • b/c passive current flow across gap junction is instantaneous
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

sign and amplitude of transmitted changes of electrical synapses

  • which is better transmitter (slow/fast potential change)
A

same sign, smaller amplitude
- ex: 10mV hyperpolarization presynaptically may lead to 1mV hyperpolarization postsynaptically

  • slow potential changes are better transmitted than fast potential changes (ex: AP)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

general purpose of electrical synapse?

A

synchronize electrical activity among populations of neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

regulation of electrical transmission

gap junctions

A
  • most gap junction channels are closed, regulated to alter fraction of open channels
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

connexin phosphorylation

  • and example

(electrical synapse- regulation of transmission)

A

extracellular signals activate protein kinases which phosphorylate connexins
- depending on connexin type, phosphorylation can have opposite effect and tend to open cap junction channels

ex horizontal cells: D1 receptor–> adenyly cyclase–> cAMP–> protein kinase A–> phosphorylation of connexins–> gap junction channels less open

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

gap junction response to intracellular Ca concentration

electrical synapse- regulation of transmission

A

gap junctions close in response to pathologically high Ca concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

differences in membrane potential between electrically connected cells

A

large differences in membrane potential between electrically connected called tend to close gap junction channels
- dependent on connexin composition

  • if membrane depolarized, can lead to closing of gap junction channels
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

electrical synapses in aplysia californica

A

motor neurons in control of ink discharge are connected via electrical synapses
- allowing them to fire synchronously, providing rapid and complete ink discharge

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

electrical synapses in fish

A
  • mauthner neurons are large reticulospinal neurons in fish and amphibia that mediate escape responses
  • in teleosts, these neurons receive mixed electrical and chemical synaptic input from auditory afferents
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

electrical synapse in retina (mammals)

A
  • allow for some processing of visual info
  • horizontal cells are for lateral inhibition of input, they are couples and allow to activate at the same time
  • horizontal cells get uncoupled, and close electrical synapse, less inhibition, photoreceptors can transmit info to bipolar cells (allow to see in dark)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

electrical synapses in neocortex

A
  • have excitatory projection neurons and inhibitory neurons (GABA)
  • interneurons, similar functions, connected via electrical synapses, activate in similar way
  • if one interneuron is depolarized from incoming chemicals, sends depolarization to connecting neurons so they can depolarize the same way
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

(chemical synapses structure)

- presynaptic bouton

A

specialization of presynaptic neuron containing cellular components required for the secretion of neurotransmitter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

(chemical synapses structure)

- synaptic vesicle

A

membrane vesicle of 35-50nm diameter
- contains 1000s of neurotransmitter molecules

  • small membrane bounded organelles within presynaptic terminal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

(chemical synapses structure)

- active zone

A

proteinacious structure at presynaptic membrane

  • required for efficient exocytosis of neurotransmitter
  • provide protein to fuse to plasma membrane to release neutotransmitters
33
Q

(chemical synapses structure)
- synaptic cleft

and width

A

extracellular space between presynaptic and postsynaptic membrane
- width 20-40nm

34
Q

(chemical synapses structure)

- postsynaptic specialization

A
  • proteinaceous structure at the postsynaptic membrane
  • contains neurotransmitter receptors, proteins of intracellular signalling cascades (ex: kinases) and scaffolding proteins- which link receptors and signalling proteins to cytoskeleton
35
Q

3 reasons why chemical synapses are not created equally

A

1) structure of postsynaptic specialization is different in inhibitory and excitatory synapses
2) vesicles containing peptide and monoamine neurotransmitters have a different ultrastructural appearance
3) different pre and postsynaptic structures can participate in synapse formation

36
Q

(chem. synapses not created equal #1)

- the different structures of postsynaptic specialization between inhibitory and excitatory synapses

A

excitatory- asymmetrical synapses

    • Grays Type I
    • post synaptic specialization is thicker than presynaptic

inhibitory- symmetrical synapses

    • Grays Type II
    • thickness of pre and postsynaptic specialization is close to same
37
Q

(chem. synapses not created equal #2)
- vesicles containing peptide and monoamine neurotransmitter have a different ultrastructural appearance (3 different types)

A

1) small synaptic vesicle with little electron density
- amino acid neurotransmitters, acetylcholine, purine neurotransmitters

2) small, electron dense- vesicles
- monoamine neurotransmitter

3) large electron-dense vesicles: synapses also contain regular synaptic vesicles with non-peptide neurotransmitter
- peptide neurotransmitter

38
Q

(chem. synapses not created equal #3)

- different pre and post synaptic structures can participate in synapse formation (6 types)

A

1) axospinous synapses
2) axodendritic synapses
3) axosomatic synapses
4) axo-axonic synapses
5) dendrodentritic synapses
6) neuromuscular junctions

39
Q

(chemical synapses)

  • axospinous synapses
A

synapses of axonal boutons onto spinous protrusions of dendrites

  • excitatory (glutamatergic) synapses
40
Q

(chemical synapses)

axodendritic synapses

A

synapses of axonal boutons onto dendritic shafts

  • inhibitory or excitatory synapses
41
Q

(chemical synapses)

axosomatic synapses

A

synapses of axonal boutons onto neuronal soma

  • frequently inhibitory synapses
42
Q

(chemical synapses)

axo-axonic synapses

A

synapses of axonal boutons onto axons or another axonal bouton

  • inhibitory synapses
43
Q

(chemical synapses)

dendrodentritic synapses

A

synapses of dendritic segments containing synaptic vesicles onto another dendrite

  • often reciprocal inhibitory synapses
44
Q

(chemical synapses)

neuromuscular junctions

A

of axonal boutons onto muscle fiber

  • excitatory (cholinergic) synapses
45
Q

(chemical synapses)

synapses made on axons..

A

exclusively inhibitory

  • can inhibit the release of neurotransmitter on the synapse
46
Q

(chemical synapses)

synapses between dendrites…

A

make synaptic contact

  • often inhibitory and reciprocal
47
Q

transmission of chemical synapses

- sequence of events (7)

A

1) an AP arrives @ presynaptic bouton, voltage-gated Na channels open
2) voltage gated Ca channels open, and Ca flows into the cytosol

3) increase cytosolic [Ca] causes synaptic vesicle docked to active zone to fuse with the plasma membrane
- neurotransmitter is released into synaptic cleft (via exocytosis)

4) neurotransmitter binds to
- ionotropic receptors (lead directly to opening ion channels)
- metabotropic receptors (leading to opening/sometimes closing ion channels via activations of GPCR (and 2nd messenger cascade)

5) postsynaptic current leads to a postsynaptic potential (change in potential of postsynaptic membranes)
6) removal of neurotransmitter by glial re-uptake or enzymatic degradation
7) retrieval of vesicular membrane from plasma membrane

48
Q

ionotropic receptors

- speed of postsynaptic responses
chemical synapses

A

ligand-gated ion channels

  • the ligand (neurotransmitter) binds to an extracellular site, leading to a conformational change in receptors membrane spanning domain, which opens ion channel
  • mediate rapid postsynaptic effects
49
Q

ioniotropic receptors allow the passage of..

A
  • they are ion selective

allow
Cl) or (Na and K) or (Na, K and Ca

50
Q

metabotropic receptors

- speed of postsynaptic responses
chemical synapses

A

G-Protein Coupled Receptors (not ion channels themselves)

  • ligand (neurotransmitter) binds to extracellular site, leading to a conformational change in receptors membrane spanning domain, which activated a G-Protein bound to the receptor
  • postsynaptic responses to activation are usually slow and long-lasting
51
Q

the activated G-protein dissociated from receptors and either…

(metabotropic receptors- chemical synapses)

A

1) binds DIRECTLY to an ion channel and modulated its conductance

or

2) bind to effector proteins/enzymes that modulate the concentrations of SECOND MESSENGERS (cAMP, cGMP or IP3) which modulate ion channels
- G-protein or second messenger-modulated ion channels are usually ion-selective

52
Q

similar function of both ionotropic and metabotropic receptors

(chemical synapses)

A

lead to conduction of ions across the postsynaptic plasma membrane

(where there is ion flow there is change in postsynaptic terminal)

53
Q

what process turn chemical transmission off?

- explain (7)

A

1) voltage gated Na channel: inactivate
2) voltage-gated K channel: open, repolarizing presynaptic membrane
3) voltage-gated Ca channel: close after repolarization of presynaptic membrane
4) ion pumps: (ex: Na/K- ATPase), re-establish ion gradients across the presynaptic membrane
5) neurotransmitter: is removed from synaptic cleft by transporters in neurons and surrounding glial cells
6) some ionotropic receptors: desentsitize and close in the continued presence of their ligand
7) postsynaptic potentials: spread throughout the dendrite and soma, and eventually dissipate (of threshold to activate voltage-gated Na channels is not reached)

54
Q

time course of postsynaptic currents and potential
– of single ligand gated ionotropic receptors and synapse
(chemical synapses)

A

single ligand- gated ionotropic receptors:
neurotransmitter causes channel to open
-channel is open only for few milliseconds, as the ligand unbinds and diffuses away

synapse: many neurotransmitter molecules exocytosed many ligand-gated channels open nearly simultaneously
- variability in timecourse of ligand unbinding causes some to channels to close later

55
Q

time course of postsynaptic current and potential

chemical synapses

A

post synaptic current= sum of all channel currents

  • fast rise tome (near simultaneous ligand binding)
  • slower time to decay (variability in ligand unbinding)

postsynaptic potential
- similar, slightly slower time course

56
Q

flux of ions across membrane is determined by… (which is)

chemical synapses

A

electrochemical gradient

- the sum of membrane potential and concentration gradient

57
Q

reversal potential for an ion if..

chemical synapses

A

membrane potential and concentration gradient oppose each other and are of same strength
- electrochemical gradient is zero

58
Q

direction of postsynaptic current is calculated by…

chemical synapses

A

using membrane potential and reversal potential of ligand gated ion channel
- if reversing potential is more positive than membrane potential –>net current is inward (negative)

  • if reversing potential is more negative than membrane potential–> net current is outward (positive)
59
Q

amplitude of postsynaptic current depends on (2)

chemical synapses

A

1) number of conductance of open ligand-gated ion channels

2) magnitude of difference between membrane potential and reversal potential

60
Q

opening of ligand gated ion channels during synaptic transmission causes…

(chemical synapses)

A

postsynaptic membrane potential to change in the direction of the reversal potential of that ion

61
Q

more different the membrane potential from reversing potential the _____ the current

A

larger the current

62
Q

when does a reversal potential occur (what is net current have to be?)

(chemical synapses)

A

reversal potential of an ion channel is the membrane potential at which the net current through the channel is ZERO

63
Q

if an ion channel is selective for single ion, its reversal potential is _____,

the reversal potential can be calculated using?

A

reversal potential is equilibrium potential
- membrane potential at which there is no electrochemical driving force for this ion

  • Nerst Equation
    Erev= reversal potential
    Vm= membrane potential

Erev= (RT/zF) ln [ion]o / [ion]i

64
Q

if an ion channel is permeable to 2 or more ions, how do you calculate

A

its reversal potentail is somewhere inbetween the equilibrium potentials for the indivudual ions

  • calculate using Goldman Equation

Erev= 58log (Pk[K]o+PNa [Na]o+PCl[Cl]i) / (Pk[K]i+PNa[Na]i+PCl [Cl]o)

65
Q

post synaptic currents and potentials change ____ with membrane potential

A

linearly

66
Q

post synaptic currents and potentials are called excitatory potentials if…

(chemical synapses)

A

excitatory postsynaptic currents and potentials (EPSC and EPSP)
- if they increase the likelihood of a postsynaptic AP occurring

  • synapses at which neurotransmitter release leads to the generation of EPSP are called excitatory synapses
67
Q

when does the post synaptic potential facilitate action potential, and when is it excitatory? (with reversing potential)

(chemical synapses)

A
  • if the reversal potential of the ligand-gated ion channels carry the post synaptic current is MORE POSITIVE than the action potential
68
Q

2 examples for excitatory synapses

chemical synapses

A

1) glutamatergic synapses in the CNS
- contain Na/K- permeable glutamate receptors

2) neuromuscular junctions
- contain Na/K- permeable acetylcholine receptors

69
Q

postsynaptic currents and potentials are called inhibitory if…

A

IPSC and IPSP if they decrease the likelihood of a postsynaptic action potential occurring

  • synapses at which neurotransmitter release leads to the generation of IPSP= inhibitory synapses
70
Q

when does the post synaptic potential inhibit the action potential generating?

A

if reversal potential of ligand-gated ion channels carrying postsynaptic current is MORE NEGATIVE than the action potential threshold

  • if Erev Vm, IPSP is depolarizing so exceed threshold– shunting inhibition
71
Q

what is the shunting inhibition of IPSP?

chemical synapses

A

if Erev > Vm

  • IPSP is depolarizing
  • tends to keep membrane potential at value more negative than the AP threshold (Erev)
  • making harder for adjacent excitatory synapses to elicit action potential
  • makes inhibitory
72
Q

example of inhibitory synapses
- which contain what receptors?

(chemical synapses)

A

GABAergic synapses in the CNS

- contain Cl permeable GABA receptors

73
Q

SUMMARY

directionality (electrical vs chemical)

A

electrical= bidirectional

chemical= unidirectional
- transmission pre to post synaptic terminal

74
Q

SUMMARY

synaptic delay (electrical vs chemical)

A

electrical is

75
Q

SUMMARY

direction of postsynaptic potential change
electrical vs chemical

A

electrical: same as presynaptic potential change

chemical: either hyperpolarizing or depolarizing
- depends on Vm and Erev of postsynaptic ligand-gated ion channels

76
Q

SUMMARY

amplitude of postsynaptic potential change
electrical vs chemical

A

electrical: fraction of presynaptic potential change; slow potential changes transmitted better

chemical: depends on Vm and Erev of ion channel involved
and on number and conductance of opened channels

77
Q

SUMMARY

transmission of presynaptic sub threshold activity, yes/no
electrical vs chemical

A

electrical: YES

chemical: NO
- transmission required presynaptic action potential
- exception: photoreceptors on bipolar cells in retina, and hair cells can release neurotransmitter in response to graded receptor potentials

78
Q

What signals can be relayed by electrical synapses? What functional roles do electrical synapses
have? Is transmission at electrical synapses regulated?

A

SIGNALS - Electrical synapses contain gap junction channels that permit passage of Na+, K+, Cl-, and Ca2+ from
one cell to the other. Second messengers such as cAMP and IP3 can also diffuse through gap junction
channels

FUNCTION - (a) Fast escape responses in invertebrates and vertebrates,
(b) synchronization of activity in
neurons of the same type (especially inhibitory interneurons, such as in the cortex and the retina)

REGULATION: Conductance of gap junction channels is regulated by, e.g., phosphorylation of connexins

79
Q

What is the reversal potential (Erev) of ion channels at a synapse?

How is the postsynaptic current related to membrane potential (Vm) and Erev ?

A
  • The reversal potential of ion channels at a synapse is the membrane potential at which the net current
    through the channels is zero.
  • If the membrane potential is more negative than the reversal potential, there is a net inflow of positively charged ions into the cell (or a flow of negatively charged ions out of the cell, depending on the ion selectivity of the channels).
  • If the membrane potential is more positive than the
    reversal potential, there is a net outflow of positively charged ions out of the cell (or an inflow of negatively
    charged ions).
  • In every case, the membrane potential moves towards the reversal potential of the ion channels