Chemical Synapses Flashcards

1
Q

Do dendritic spines receive excitatory, inhibitory or both types of synapses?

A

Dendritic spines receive excitatory synapses.

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2
Q

True or false: axons connect only once with a given neuron (more connections would be redundant)

A

False. Axons can make multiple contacts with a given neuron (different synapses) and this is key to strengthen their connections and to spatial integration..

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3
Q

True or false: when AP reach axon terminal, vesicles with neurotransmitters (NTs) are released to the synaptic cleft inducing a post-synaptic potential.

A

False. Vesicles are not released, only the NTs are released into the synaptic cleft. Vesicles only fuse with the pre-synaptic membrane.

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4
Q

What are the advantages and drawbacks of chemical synapses as opposed to gap junctions?

A

Even though they are slower, the modulation and plasticity allowed far outweighs the former and underpins memory and learning.

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5
Q

Compare ionotropic and metabotropic receptors and their roles.

A

Ionotropic receptors undergo simple fast conformational changes upon NT binding (or voltage changes or other gating stimuli) opening the channel and allowing immediate ion flow (very fast: <1ms), whereas metabotropic receptors (G-protein coupled receptors) release second messenger which triggers a cascade of signaling pathways and hence it’s much slower (>50ms), however it allows modulation (key for instance in sensory adaptation), tighter control, plasticity (key to memory and learning) and amplification (key to some sensory modalities to increase sensitivity). Ionotropic receptors are involved in AP generation and propagation, whereas metabotropic receptors modulate synapse strength, making it easier or harder to trigger an AP.

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6
Q

Complete the blanks: ________ in the pre-synaptic membrane bind _______ in the NT vesicle. Then _________ (also in the vesicle) along with other protein factors (SNAP and NSF proteins) bind t-SNARE/v-SNARE complex bringing vesicle and membrane closer together. Then ______ hydrolysis gets rid of SNAP and NSF allowing _______ and ________ allows conformational changes, mediating ______ release once vesicle fuses to membrane.

A

SNAP-25/synapsin (t-SNAREs) …. VAMP (v-SNAREs) … synaptotagmin … ATP … fusion … Ca2+ … NT…

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7
Q

Describe the events leading up to the release of NT

A
1- AP travels along presynaptic axon
2- Bouton becomes depolarised
3- Voltage-gated Ca2+ channel open
4- [Ca2+] in terminal rises
5- Vesicle and cell membranes fuse
6- Pore opens releasing NT
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8
Q

Which receptor is a “coincidence detector” and why?

A

NMDAR because it detects the coincidence of:

  1. Glu release due to presynaptic depolarisation
  2. postsynaptic depolarisation (from any source)
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9
Q

What are the 3 types of ionotropic Glu receptors? What are their differences?

A

AMPAR and kainate receptors let monovalent cations like Na+ and K+ flow once they open upon Glu binding. NMDARs are permeable to both Ca2+ and monovalent cations and open upon Glu (+ Gly) binding (occupation of both Glu and a Gly binding sites is required for activation but Gly site is very high affinity and there is normally enough Gly extrasynaptically to saturate this site and thus it’s not dependent on Gly release)

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10
Q

What happens when AMPARs open after Glu binding?

A

AMPAR is equally permeable to all monovalent ions (mainly K+ and Na+), therefore, once opened upon Glu binding, Na+ inflow will be much higher than K+ outflow due to the negative RMP (higher Na+ driving force), depolarizing the postsynaptic membrane.

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11
Q

What happens when NMDARs open after Glu binding?

A

As soon as NMDRs open, intracellular Mg2+ blocks channel so there’s no ion flow. For negative Vm, channel is blocked by Mg2+. However, if there is depolarization, the more positive Vm allows Mg2+ to get out, in turn allowing Ca2+ (key to EPSP due to high charge density) and Na+ influx

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12
Q

What are the main excitatory and inhibitory NTs and why?

A

The main excitatory NT is Glu, causing depolarization (EPSP), that is, increases probability of cell firing, mainly due to the inflow of Na+ (and Ca+). The main inhibitory NTs are Gly and GABA which cause hyperpolarization, that is, decrease the probability of the cell firing, due to inflow of Cl-.

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13
Q

How is Cl- inflow represented in V(t) and I(t) neurophisiological recordings?

A

Current is defined by the flow of positive charges. Hence, Cl- inflow generates an outward current (upwards in I(t)) and since Cl- is negative it will further decrease the Vm and lead to hyperpolarization (downwards in V(t)).

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14
Q

At what voltage would you get equal flow of Na+

into the cell and K+ out of the cell through AMPARs? And in what direction would the current flow during the overshoot?

A

Near 0mV because AMPARs are equally permeable to Na+ and K+ so the ion flow only depends on the driving force (Vm and E). Hence, since E(Na+)=+62mV and E(K+)=-80mV, AMPA equilibrium potential would be close to -10mV (nearly 0mV). If Vm>0mV, the current flows outwards (K+). Conversely, if Vm<0mV, the current flows inwards (Na+).

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15
Q

What is the GABA equilibrium potential? In what direction will the current flow at RMP?

A

GABA equilibrium potential is roughly -80mV thus at RMP the current would flow outwards (since Cl- are anions these ions would flow inwards)

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16
Q

Describe and explain the I(V) curve for NMDARs?

A

NMDA equilibrium potential close to 0mV (due to dominance of K+ and Na+ flow) and the current flows outwards as Vm increases, similar to AMPARs but at slightly higher voltages due to small Ca2+ inward current. For small negative Vm, the current flows inward but as Vm decreases there will be n current due to Mg2+ blockage.

17
Q

What is and what influences the I(V) gradient?

A

The gradient is the conductance and is determined by the number and conductance of the channels.

18
Q

How many channels are opened and how much current is generated by a single vesicle of NTs?

A

10s of channels => 10s of pAs

19
Q

What determines the amplitude of current at a fixed potential in the post-synaptic membrane?

A
  1. number and g of postsynaptic receptors per site
  2. probability of release of NT
  3. number of sites
20
Q

Would Na+ or K+ show greater current flow at –70mV for activated AMPARs?

A

Na+ due to higher driving force.

21
Q

What will be the maximum voltage change due to a

50 pA glutamatergic current in a cell with 400 MOhms membrane resistance?

A

20mV

22
Q

And what will be the maximum voltage change due to a
50 pA glutamatergic current in a cell with 400 MOhms membrane resistance, after the GABARs opening decreased resistance by half?

A

10mV

23
Q

What determines the potential change due to a given current?

A

Resting input resistance (V = IR ), determined by leak conductances & other conductances active at the time, and the capacitance (membrane time constant, T(ms) = RC), which means maximum voltage is only reached if current flows for long enough compared to T(ms)

24
Q

How does inhibition act?

A

Not only it sends the voltage in the other direction (hyperpolarization), but it also makes the cell more leaky (decreases resistance)