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BIOL2052 S1 > Molecular Neuroscience > Flashcards

Molecular Neuroscience Flashcards

1
Q

Why is the brain described as being a non-vital organ?

A

As if you are brain dead you can survive

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2
Q

Where does transcription and translation occur?

A
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3
Q

What have promotor studies shown?

A
  • Identifies mouse mutants
  • Identifies disease forming mutations in humans
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4
Q

Which of the following are regulated by nerve activity?

  • Gene expression in DNA
  • Maturation in RNA
  • ALternate splicing in RNA
  • protein function
A

All of them are regulated by nerve activity

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5
Q

For the following flow, what does each split into?

  • DNA
  • RNA
  • Proteins
  • Protein function
A
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6
Q

Whats required for Glutamate to turn into GABA?

A

Glutamate decarboxylase

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7
Q

Tell me about glutamate

A
  • A naturally occuring AA, can get from diet
  • The most abundant and excitatory AA in the brain
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8
Q

Tell me about GABA

A
  • Has to be synthesised, not occuring naturally
  • An inhibitory AA
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9
Q

What is the GAD gene recognised by? What is this to ensure?

A

GAD gene is recongised by transcription factors to ensure gene is selectivity expressed in GABA neurons

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10
Q

Whats the difference between enhancers and repressors?

A

Enhancers: increase the rate of transcription of genes

Repressors: Decrease the rate of transcription

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11
Q

What is cytoskeleton first born ?

A

Born as a non-neuronal cell mature and cells-develop processes

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12
Q

In the cytoskeleton; polarity of processes (tend to be ended)

What does the axon and dendrite form?

A

Axon: giving the presynaptic nerve terminal

Dendrite: Giving the postsynaptic nerve terminal

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13
Q

How does the cytoskeleton retain its shape?

Why is it important?

A

Retain this shape basic polarity static view but actually they are highly dynamic

Cytoskeleton is the important molecular component

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14
Q

What is the cytoskeleton made up of?

A

Microtubules

Actin filaments

Intermediate filaments

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15
Q

What dimers are the cytoskeleton made up of?

A

Alpha and beta dimers build the hollow tube giving a +ve and -ve end

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16
Q

What monomers make the F-actin filaments ?

A

G-actin monomers

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17
Q

How is the following arranged in a neuron?

  • actin cytoskeleton
  • Microtubules in axon and dendrite
  • Neurofilament

What regulatory proteins are present?

A
  • Dendrites use both orientations of microtubules
  • Molecules define shape of neuron
  • Associated protein found in sub compartments
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18
Q

What do kinesins and other motors do?

A

Move things around

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19
Q

What do kinesins bind to?

A
  • cargo or proteins that need to be transported
  • binds to microtubules
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20
Q

What do kinesins use?

A

ATP activity

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21
Q

What do kinesins walk along and where do they move proteins?

A

Kinesins move along the microtubule

They move proteins to extremities of the processes where the major signalling happens

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22
Q

Is kinesin a motor protein?

A

yes

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23
Q

What do Dyneins do?

A

They recognise mictotubules and move from +ve to -ve end (retrograde transport)

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24
Q

What does the Na+/K+ ATPase pump, pump?

A

3 Na+ out

2 K+ in

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25
Q

What are the levels (mM) of sodium inside and outside of the cell?

A

More sodium outside (142 mM) than inside (10mM)

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26
Q

What are the levels of potassium (mM) inside and outside of the cell?

A

More potassium inside (140mM) than outside (4mM)

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27
Q

What the major anion in the cell and what are its levels inside and outside of the cell?

A

Major negative ion chloride (Cl- is an anion) is higher outside (103mM) inside (4mM)

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28
Q

What is the minor ion in the cell and its levels (mM) inside and outside of the cell?

A

Minor ion Calcium outside (2mM) very low inside (100 nM)

29
Q

What is the RMP set up by?

A

RMP is set up by a leak of K+ in the membrane, not by the ATPase ion pump

30
Q

What two types of communication are used for intercellular communication?

A
  • electrical communication
  • chemical communication
31
Q

What is the sodium channel made up of?

A

one protein sequence that contains 4 domains which are linked via a single polypeptide chain in order to make an ion channel

32
Q

What does each domain of the sodium channel have?

A

a voltage sensor and 1/4 of the pore

33
Q

For Na+ channels, whats the treshold for activation and inactivation?

A

Activation= -50mV

Inactivation= 0 mV

34
Q

What are potassium channels made up of?

A

Made up of one protein sequence that contains 1 domain

made of isolated polypeptide chains

35
Q

What does each potassium channel domain have?

A

A voltage sensor and 1/4 of the pore. Come together in a tetramer to make a functional channel

36
Q

Whats the threshold for activation and inactivation in potassium channels?

A

Activation: 0 mV

Inactivation: -50 mV

37
Q

Do K+ and Na+ open at the same RMP?

A

No

38
Q

Tell me about how an action potential arises and the different voltages seen and what ion channels open/close?

A
  1. Voltage channels are closed and the Potassium (K+) leak channel and the sodium (Na+) pump maintain the resting membrane potential of -70 mV. The Sodium/Potassium Pump (ATPase) is responsible for maintaining the membrane potential at -70mv, the protein actively pumps three sodium ions out of the cell and pumps two potassium ions into the cell.
  2. The neurone becomes stimulated. The voltage gated sodium channels begin to open and the membrane potential begins to slowly depolarises and sodium enters the cell down its concentration gradient. All the voltage-gated Sodium channels open when the membrane potential reaches around -55 mV and there’s a large influx of Sodium, causing a sharp rise in voltage. As the potential nears +30mV, the rate of depolarisation slows down as the voltage-gated Sodium channels become saturated and inactivate, preventing further sodium ions from entering the cell.
  3. Voltage gated potassium channels open, and potassium leaves the cell down its concentration gradient. The depolarization of the cell stops and repolarisation can occur through these voltage-gated Potassium channels.
  4. Voltage gated sodium channels are completely deactivated and potassium floods out through the voltage gated potassium channels,
  5. Voltage gated potassium channels are slow to close, and therefore hyperpolarisation occurs. This is where the membrane potential drops below the resting potential of -70 mV as potassium continues to leave.
  6. Once the voltage gated potassium channels close, the resting state can be re-established through the Potassium leak channel and Sodium pump.
39
Q

What is the speed of the ion channels opening/closing dependent on?

A

Speed is intrinsic to protein structure. The protein structure controls the speed in which the proteins react to membrane potential change

40
Q

What are the two ways to bridge the synaptic gap?

A
41
Q

What are the principles of chemical transmission?

A
42
Q

What are the stages to chemical transmission?

A
  1. Stimulated neuron opens ion channels including those that allow Ca2+ into nerve terminal.
  2. Ca2+ is sensed. Recognized by a protein that binds Ca2+ and changes its conformation (Synaptotagmin).
  3. Change in conformation allows proteins SNARE proteins to promote fusion via a vesicle/plasmamembrane protein complex.
  4. Vesicle fuses with the plasma membrane, NT released and diffuses into the synaptic cleft.
  5. Receptors bind NT and these proteins are ion channels.
  6. NT binding opens (or is gates) receptor channel, allows ions to flow and change distribution across membrane.
  7. Excite by depolarizing the membranes {positive signal}.
  8. Inhibit by hyperpolarizing the membrane {negative signal}.
  9. Chemical signal is terminated by diffusion away or reuptake from the synaptic cleft
43
Q

Initiating transmitter release by opening ion channels

A
44
Q

How is transmitter release across the synapse initiated?

A

When an action potentail arrives at the synapse, it initiates the opening of calcium gates channels

45
Q

What is Ca2+ couple to?

A

vesicle fusion

46
Q

What is the calcium sensor in synapses and what does it do?

A

A protein called Synaptotagmin recognises Ca2+ and changes its conformation

47
Q

What two things act as fusion promoting protein, making a vesicle/ plasma membrane complex

A

The vesicle (v) and target membrane (t) SNARE proteins

48
Q

Tell me about Synaptotagmin and its role in the synapse?

A

Protein domains that bind Ca2+

Changes conformation when bound Ca2+

Allows vesicle to see the signal from Ca2+

Protein domains: Synaptotagmin contains two C2 domains, referred to as the C2A and C2B domains, that bind Ca2+ with similar properties and affinities

49
Q

What does Ca2+ synaptotagmin promote?

A

Promotes vesicle SNAREs and plasmamembrane SNAREs to complex using complementary protein interaction domaines (i.e. coil-coil domains) this promotes fusion

50
Q

Whats Synaptobrevin?

A

A protein complex which helps to drive fusion.

They are small integral membrane proteins of secretory vesicles, specialised secretory organelles that actively accumulate neurotransmitters and participate in their calcium-dependent release by exocytosis

51
Q

Whats Syntaxin?

A

A family of membrane integrated Q-SNARE proteins participating in exocytosis

52
Q

Whats SNAP-25?

A

Component of SNARE complex. Proposed to account for the specificity of membrane fusion by forming a tight complex that brings the synaptic vesicle and plasma membranes together

53
Q

Tell me about the the stage of the action potential where the action potential is released, diffusion and reception

A
54
Q

Tell me about receptor activation and transmitter action termination

A
55
Q

How are receptors inhibited or excited during neurotransmitter release?

A

Inhibited by…

  • hyperpolarised the membrane (negative ion Cl- influx)

Excited by…

  • Depolarising the membranes (positive ions Na+ influx)
56
Q

Where are the major excitatory synapses located?

Whats used as a transmitter?

A

On the dendrites

use Glutamate as the transmitter

57
Q

Where are the major inhibitory synapses located?

Whats used as a neurotransmitter?

A

On cell body

Use GABA or glycine as the transmitter

58
Q

What is a Axo-dendritic synapse and a Axo-somatic synapse?

A
59
Q

Tell me whether the following synapses are often symmetric or asymmetric?

  • Glutamatergic
  • GABA/glycine
A
60
Q

In a glutamatergic synapse

  • What attaches to the stored glutamate?
  • Tell me about the specialisation organiser
A
61
Q

In a GABA/glycine synapse

What attaches to the stored glycine?

Tell me about the specialisation organiser

A
62
Q

Tell me about the key features of glutamate receptors?

A
  • Four subunits to make ion channel
  • Glutamate binding site on outside
  • Cation channel
  • Bind to molecules like PSD-95 on inside
  • Postsynaptic cell
63
Q

Tell me about the key features of glycine/ GABA receptors?

A
  • Five subunits to make ion channel
  • Glycine binding site on outside
  • Anion channel
  • Bind to Gephyrin on the inside
  • Postsynaptic cells
64
Q

Key features on excitatory and inhibitory receptors

A
65
Q

Organising molecules are multi-domain proteins and can help with segregation

A
66
Q

Simple model as a primer for a complex synaptic glue

A
67
Q

A real impact of molecular neurobiology in understanding and treating disease

A
68
Q

Consider the following…

A

BIOL2052 S1 (10 decks)

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