GABA + Glycine Flashcards
What is GABA?
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system (CNS).
Approximately one third of synapses utilise GABA as their neurotransmitter
How is GABA synthesised and stored?
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How is GABA reuptake and degraded?
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What are the 2 types of receptors GABA binds to?
Ionotropic and metabotropic receptors
What are the specific GABA receptors?
GABAa and GABAb
Describe the structure of a GABAa receptor
What structure does it have?
What are the binding sites?
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Describe the structure of a GABAb receptor
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What does GABA cause?
Inhibitory neurotransmitters (e.g. GABA) can cause neuronal membrane hyperpolarisation – displacement of a membrane potential towards a more negative value.
What is the cerebellum and what is its function?
The cerebellum The cerebellum (or “little brain”) is a prominent hindbrain structure – it accounts for approximately 10% of the human brains volume.
Cerebellum function?
• The cerebellum does not initiate movement but detects differences in “motor error” between an intended movement and the actual movement
• Aids the motor cortex to produces precise and co-ordinated movement
Is the function of the cerebellum conserved?
- It has been shown that, for example, the cerebellum is important in synchronisation of movement with musical rhythm
- This may be widespread across the animal kingdom…
Describe the projections from the cerebellum
Purkinje cells are are a class of GABAergic neurons that comprise the principle projection neurons of the cerebellar cortex.
- Purkinje cells have elaborate dendritic trees that receive convergent input from cells in the molecular layer
- Purkinje cells send GABAergic projections to deep cerebellar neurons
- Purkinje cell output to the deep cerebellar neurons generates an error connection signal that can modify movements
- This provides the basis for real-time control of precise and synchronous movement
How is glutamate converted to GABA?
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What is epilepsy and what does to much excitation cause?
Epilepsy is a brain disorder characterised by periodic and unpredictable seizures mediated by the rhythmic firing of large groups of neurons.
Too much excitation? -> increase inhibition*Other anti-epileptics directly decrease excitation
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What is anxiety?
Anxiety can be defined as a feeling of unease (e.g. worry or fear), which can range from mild to severe.
What are anxiety disorders and anxioytics?
(e.g. benzodiazepines – GABAA receptor)
What is glycine?
Glycine is the second major inhibitory neurotransmitter in the central nervous system (CNS).
- Glycine was first identified in the spinal cord and brainstem in 1965
- In the 1967, glycine was shown to inhibit action potential firing in spinal neurons
- Glycine most commonly found as an inhibitory neurotransmitter in the ventral horn, the location for spinal interneuron terminals
- However, our understanding of the glycine receptor is lagging behind the GABA receptors – in part due to limited allosteric modulators of the receptor
How is glycine synthesised and stored?
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Synthesised in the nerve terminals
Transported into vesicles by vesicular inhibitory amino acid transporters (VIAAT)
How is glycine reuptaken and degraded?
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Describe the structure of the glycine receptor
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Describe Hyperekplexia and glycine neurotransmission
Hyperekplexia is a rare disorder characterised by hypertonia (increased muscle tone) and an exaggerated startle response.
• Symptoms can manifest in relation to unexpected stimuli (e.g. loud noises)
What is the role of glycine?
• Gene mutations (e.g. glycine receptors, glycine transporters) can disrupt normal glycinergic neurotransmission
• Can lead to neuronal hyperexcitability (by impairing glycinergic inhibition)
• Leads to hypertonia and exaggerated startle response
Startle (or myotonic, fainting) goats…
- In startle goats, there is a decreased muscle chloride conductance – can be caused by glycine receptor mutations
- As the goats mature, GABAA receptors are upregulated to compensate
