Neurotransmitter System II: Glutamate & Glycine Flashcards

1
Q

What is GABA as a neurotransmitter?

A
  • Gamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system
  • First identified in the mammalian nervous system in 1950
  • Around one third of synapses utilise GABA as a neurotransmitter
  • It’s most commonly found as a inhibitory neurotransmitter in local circuit interneurons
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2
Q

How is GABA synthesised?

A
  • Glutamate is converted to GABA via a glutamate decarboxylase enzyme. Uses pyridoxal phosphate
  • Synthesised in the nerve terminals
  • Transported into vesicles by vesicular inhibitory amino acid transporters
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3
Q

Describe the re-uptake of GABA

A
  • Goes from the presynaptic terminal to the post synaptic neuron via GATS
  • Neurons and glial contain high affinity Na+ dependent GABA reuptake transporters (GATS)
  • Neurons = GAT-1
  • Glial cells = GAT-
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4
Q

Describe the degradation of GABA

A
  • GABA converted to succinic semialdehyde via the GABA trans animate enzyme (GABA-T)
  • This is then converted to succinic acid via the succinic semialdehyde dehydrogenase enzyme (SSADH)
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5
Q

What are the two broad family of receptors?

A
  • Ligand gated ion channels (ionotrophic)
  • G protein coupled receptors (metabotropic)
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6
Q

What type of receptors does GABA bind to?

A
  • Binds to both Ionotropic and metabotropic GABA receptors
  • ionotropic receptors = GABAA (LGIC)
  • Metabotropic receptors = GABAB (GPCR)
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7
Q

Describe the GABAB receptor

A
  • G protein coupled receptor
  • Has a Cysteine rich domain
  • Has a 7 transmembrane domain
  • Dimers: Heteromers GABAB1 and GABAB2
  • Watch lecture for this bit
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8
Q

What can inhibitory neurotransmitters cause?

A
  • Can cause neuronal membrane hyperpolarisation
  • Which is the displacement of the membrane potential towards a more negative value
  • Watch lecture
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9
Q

What is the cerebellum as a part of the brain?

A
  • A prominent hind structure
  • Accounts for approximately 10% of the human brains volume
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10
Q

What is the function of the cerebellum?

A
  • Detects differences in Motor error between an intended movement and the actual movement
  • Aids the motor cortex to produce precise and coordinated movement
  • Doesn’t initiate movement
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11
Q

Is the function of the cerebellum conserved?

A
  • Its been shown that the cerebellum is important in synchronisation of movement with musical rhythm
  • This could be widespread across the animal kingdom
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12
Q

What are Purkinje cells?

A

A class of GABAergic neurons that comprise the principle projection neurons of the cerebellar cortex

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13
Q

Describe the structure of purkinje cells

A

Have elaborate dendritic trees that receive convergent input from cells in the molecular layer

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14
Q

What is the function of purkinje cells?

A
  • They send GABAergic projections to deep cerebellar neurons
  • Purkinje cell output to the deep cerebellar neurons which generates an error connection signal that can modify movements
  • This provides the basis of real time control of precise and synchronous movement
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15
Q

How is GABA and glutamate balanced in the brain?

A
  • GABA and glutamate are the major neurotransmitters in the brain
  • Both work together to control the brains overall level of excitation
  • In one step, the major neurotransmitter is converted into the other major neurotransmitter in the brain
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16
Q

How is Glutamate converted into GABA?

A
  • Via a decarboxylase (GAD) enzyme which also contains pyridoxal phosphate
  • GABA is then produced from Glutamate
17
Q

What is Epilepsy?

A

A brain disorder characterised by periodic and unpredictable seizures mediated by the rhythmic firing of large groups of neurons

18
Q

How does epilepsy work?

A

GABAA receptor enhancers: Barbiturates Benzodiazepines
GAT blockers: Tiagabine
GABA transaminase inhibitor: Vigabatrine
GAD modulators: Gabapentin Valproate
Prodrug: Progabide

19
Q

What is anxiety?

A

Can be defined as a feeling of unease (worry/fear) which can range from mild to severe

20
Q

What is Glycine?

A

The second major inhibitory neurotransmitter in the central nervous system

21
Q

How is glycine synthesised in the body?

A

3 phosphoglycerate (glycolysis) -> Serine -> glycine via serine hydroxymethyl transferase enzyme

22
Q

Where is glycine synthesised?

A

In the nerve terminals

23
Q

Where is the Glycine then transported to?

A

Transported into vesicles by vesicular inhibitory amino acid transporters (VIAAT)

24
Q

Describe the re-uptake of Glycine

A
  • Goes from the presynaptic terminal to the post synaptic neuron via GlyT
  • Neurons and glial contain high affinity Na+ dependent glycine re-uptake transporters (GlyTs)
  • Glial cells = GlyT-1
  • Neurons = GlyT-2
25
Q

Describe the degradation of Glycine

A

Glycine is converted into Serine via the Serine hydroxymethyl-transferase enzyme

26
Q

What type of receptor does glycine have?

A

Ligand gated Cl- channel

27
Q

Describe the glycine receptor

A
  • Ligand gated Cl- channel
  • Has a pentameric structure containing 4 ã subtypes (ã1-ã4) and one β subtype
  • 3α12β or 4α1β most common configuration
  • Agonist/antagonist binding sites unclear – although plant alkaloid strychnine potently blocks glycine receptors
28
Q

What is Hyperekplexia?

A
  • A rare disorder characterised by hypertonic (increased muscle tone) and an exaggerated startle response
  • Symptoms can manifest in relation to unexpected stimuli
29
Q

What is the role of glycine in Hyperekplexia?

A
  • Gene mutations can disrupt normal glycinergic neurotransmission
  • Can lead to neuronal hyperexcitability
  • Leads to hypertonia and exaggerated startle response
30
Q

What happens in startle goats?

A
  • There is descended muscle chloride conductance
  • Can be caused by glycine receptor mutations
  • As the goats mature, GABAA receptors are unregulated to compensate