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NEUR3310 Neuroscience > Lecture 3: Neurotransmitters and Their Receptors > Flashcards

Lecture 3: Neurotransmitters and Their Receptors Flashcards

1
Q

Broadly speaking, chemical synaptic transmission occurs in 4 steps:

A

1) Synthesis and storage of the neurotransmitter in the presynaptic neuron

2) Release of the neurotransmitter by the presynaptic neuron into the synaptic cleft

3) Interaction of the neurotransmitter with receptors/ion channels/transporters in the postsynaptic membrane

4) Removal of the neurotransmitter

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2
Q

Neurotransmitters can also bind to…. in the presynaptic membrane

A

Neurotransmitters can also bind to:
- receptors/ion - channels/transporters

….in the presynaptic membrane

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3
Q

Definition of a neurotransmitter is not
so clear, but in principle, the chemical substance should SATISFY THE FOLLOWING CRITERIA: 4

A

1) SYNTHESISED in the presynaptic neuron

2) Is PRESENT in the PRESYNAPTIC
terminal and is RELEASED in
AMOUNTS that can CAUSE a DEFINED ACTION ON THE POSTSYNAPTIC NEURON OR ORGAN (e.g. muscle)

3) If DELIVERED EXOGENOUSLY in “reasonable” concentrations, it MIMICS THE ACTION OF THE ENDOGENOUS NEUROTRANSMITTER (e.g.
activates the same ion channels)

4) There is a SPECIFIC MECHANISMS TO REMOVE IT FROM THE SYNAPTIC CLEFT

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4
Q

Small molecule neurotransmitters: vs NEUROACTIVE PEPTIDES (larger)

PACKAGING

A
  1. SMALL MOLECULES
  2. Low molecular weights
  3. Packaged in small vesicles approx 40nm in diameter
  4. NEUROACTIVE PEPTIDES
  5. Low molecular weights
  6. Packaged in LARGE VESICLES approx 70-250nm in diameter
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5
Q

Small molecule neurotransmitters: 6

A
  1. Several classes of small molecule transmitters
  2. Many act as neuromodulators
  3. Neurotransmitters are normally discussed in the context of neuron-neuron communication
    …..4.Mostly 1-1
  4. Neuromodulators affect
    groups/populations of neurons
    …….6. Not 1-1
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6
Q

List of Small-molecule transmitter substances and their precursors…

A

slide 5

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7
Q

Small molecule neurotransmitters …labelled ones

category vs peptide

A

‘Hypothalamic realeasing hormones’:
1. thyrotropin-releasing hormone
2. gonadotropin-releasing hormone
3. somatostatin
4. corticotropin-releasing hormone
5. growth hormone-releasing hormone

‘Neurohyphyseal hormones’:
1. Vassopressin
2. oxytocin

‘Pineal Hormones’
1. Melatonin

Other
1. Neuropeptide

more in Slide 6

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8
Q

Understanding what GLUTAMATE IS: 5

A
  1. Major “EXCITATORY neurotransmitter in
    the nervous system
  2. Activation of glutamate receptors
    “excite” neurons, causing MEMBRANE DEPOLARISIATION
  3. Synthesised from GLUCOSE (Krebs cycle) or glutamine (glial cells)
  4. Astrocytes recycle GLUTAMATE and convert it back to GLUTAMINE which is
    “INACTIVE”

….5. Ready to RESUPPLY neurons

ALSO GABA

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9
Q

Glutamate

A

SLIDE 7 AND 8

PRODUCTION AND RECYCLING PROCESS DIAGRAMS

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9
Q

What are the two categories of glutamate receptors, and what distinguishes them? = 2

A

Categories:

  1. Ionotropic receptors, which are ligand-gated ion channels.
  2. Metabotropic receptors, which are G protein-coupled receptors.
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10
Q

Name the three subtypes of ionotropic glutamate receptors. = 3

A

Subtypes:

  1. NMDA receptor (N-methyl-D-aspartate)
  2. AMPA receptor (a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)
  3. Kainate receptor
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11
Q

What are ionotropic glutamate receptors, and what happens upon glutamate binding? = 4

A
  1. Definition:
    ‘Ionotropic glutamate receptors are ligand-gated ion channels.’

Upon Binding:
2. Glutamate binds to the ligand-binding domain, causing a conformational shift.

  1. This shift changes the angle of the transmembrane domain, opening the pore.
  2. It leads to an influx of cations such as Na, K, Ca, etc.
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12
Q

What are some key characteristics of NMDA receptors? = 4

A
  1. Composition:
    Composed of GluN subunits.
  2. Localization:
    Usually co-located with AMPA receptors.
  3. Function:
    Mediates the slower component of excitatory neurotransmission.
  4. Permeability:
    Exhibits high permeability to calcium and other cations.
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13
Q

What is the role of the voltage-dependent magnesium block in NMDA receptors? = 3

A
  1. Function of Magnesium Block:
  2. The magnesium block prevents cation flow through the NMDA receptor channels when the membrane is at resting potential.
  3. Upon membrane depolarization, the magnesium block is removed, allowing cations to flow through the channels without requiring a conformational change.
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14
Q

What are silent synapses, and what receptors do they typically lack?

A

Definition:
— Silent synapses are excitatory synapses that contain NMDA receptors but lack AMPA receptors.

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15
Q

What is the difference in the timing of activation between AMPA and NMDA receptors?

= 3

A
  1. Activation Timing:
  2. AMPA receptors are rapidly activated by glutamate at the synapse.
  3. NMDA receptors are activated later, after the removal of the magnesium block.
16
Q

Define silent synapses and explain their receptor composition. = 3

A
  1. Definition:
    Silent synapses are synapses that lack AMPA receptors.
  2. Receptor Composition:
    …..3. They typically contain NMDA receptors but lack AMPA receptors.
17
Q

What is required for the opening of NMDA receptors, and what role does glycine play?

= 4

A
  1. ‘Requirement for Opening:’
    - The opening of NMDA receptors requires the binding of extracellular glycine.
  2. Role of Glycine:

….3. Both the glutamate and glycine sites on the NMDA receptor must be occupied for the channel to open.

…..4. Under “normal” conditions, there is enough extracellular glycine to allow the channel to open when glutamate is released.

18
Q

What are ionotropic glutamate receptors, and how do they function? = 2

A
  1. Definition:
    Ionotropic glutamate receptors are ligand-gated ion channels.
  2. Function:
    They allow for the movement of cations across the cell membrane upon binding of the neurotransmitter glutamate.
19
Q

What are metabotropic glutamate receptors (mGluRs), and how many subtypes do they have?

A
  1. Definition:
    Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors.
  2. Subtypes:
    There are 8 different subtypes of mGluRs, named mGluR1-8.
20
Q

How are metabotropic glutamate receptors functionally subdivided, and what is their mechanism of action? = 4

A
  1. Subdivision:
    …..2…. Metabotropic glutamate receptors are subdivided into three groups.
  2. Mechanism of Action:
    …..4….. Glutamate binding to the G protein-coupled receptor (GPCR) activates a signalling cascade, leading to calcium influx through indirect ion channel opening and/or second messenger signalling.
21
Q

What is the role of GluRs (Glutamate Receptors) in the nervous system? = 2

A

Function:

  1. GluRs mediate “excitatory” neurotransmission in the nervous system.
  2. They are crucial for synaptic plasticity.
22
Q

How do AMPA receptors and NMDA receptors contribute to synaptic plasticity?

AMPA

A

MPA Receptors:

  1. AMPA receptors are added or their density is increased at excitatory synapses to strengthen synapses.
  2. This process contributes to long-term potentiation (LTP), a mechanism associated with synaptic strengthening and learning.
23
Q

How do AMPA receptors and NMDA receptors contribute to synaptic plasticity? = 2

A

NMDA Receptors:

  1. NMDA receptors are removed or their density is decreased at excitatory synapses to weaken a synapse.
  2. This process contributes to long-term depression (LTD), a mechanism associated with synaptic weakening and forgetting.
24
Q

What is the role of GABA in the nervous system,

and how does it affect neuronal activity?

A
  1. Role:
    — GABA is the major inhibitory neurotransmitter of the nervous system.
  2. Effect on Neuronal Activity:
    — Activation of GABA receptors inhibits neurons, leading to the generation of inhibitory postsynaptic potentials (IPSPs).
25
Q

How is GABA synthesized, and what removes it from the synapse? = 2

A
  1. Synthesis:
    - GABA is synthesized from glutamine.
  2. Removal from Synapse:
    - GABA is removed from the synapse by GABA transporters located on the presynaptic neuron and on astrocytes.
26
Q

What are the two subtypes of GABA receptors, and how do they function? = 4

A
  1. GABA (A) receptors
  2. GABA (A) receptors OPEN CHLORIDE CHANNELS, leading to CHLORIDE INFLUX and MEMBRANE HYPERPOLARISATION.
  3. GABA(B) receptors
  4. GABA(B) receptors INDIRECTLY OPEN POTASSIUM CHANNELS, , resulting in POTASSIUM EFFLUX AND MEMBRANE HYPERPOLARISATION.
27
Q

Differentiate between the two types of GABA receptors in terms of their ionotropic and metabotropic properties. = 4

A
  1. GABA(A) Receptors:
  2. Ionotropic receptors
  3. GABA(B) Receptors:
  4. Metabotropic receptors
28
Q

What is the effect of activating GABA receptors at physiological resting membrane potentials,

and what about at hyperpolarized resting membrane potentials? = 4

A
  1. Physiological Resting Membrane Potentials (~-65mV):
    …..2. Activation of GABA receptors causes hyperpolarization.
  2. Hyperpolarized Resting Membrane Potentials (~-80mV):
    ….4. Activation of GABA receptors causes depolarization.
29
Q

Where are GABAA receptors primarily located, and what types of inhibition do they mediate? = 2

A
  1. Location:
    GABAA receptors are primarily located post-synaptically.
  2. Inhibition Types:
    They mediate both fast and tonic inhibition.
30
Q

Describe the distribution and function of GABAA receptors at the synapse and extra-synaptically. = 5

A
  1. Synaptic Location:
    …..2. GABAA receptors are located at the synapse, mediating fast inhibition.
  2. Extra-synaptic Location:
    …..4. GABAA receptors are also located extra-synaptically, mediating tonic inhibition.
  3. Function:
    Activation of extra-synaptic receptors occurs through volume transmission.
31
Q

Where are GABAB receptors located, and how do they function in terms of ion channels and signaling pathways = 2

A
  1. Location:
    — GABAB receptors are located on glial cells and both pre- and post-synaptic neurons.
  2. Function:
    They indirectly open potassium or calcium channels via G-protein secondary messenger systems.
32
Q

What are the effects of activating pre- and post-synaptic GABAB receptors? = 4

A
  1. Pre-synaptic Activation:
    …2. Inhibition of the presynaptic neuron and calcium-dependent neurotransmitter release (auto-reception).
  2. Post-synaptic Activation:
    …4. Activation of potassium channels leading to slow hyperpolarization.
33
Q
A
33
Q

Under what conditions can the function of GABAB receptors reverse

A

Pathological Condition:

The function of GABAB receptors can reverse under pathological conditions.

NEUR3310 Neuroscience (18 decks)

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