Neuroscience Chapter on GABA and Glycine

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Questions and Answers

Which subunit of the GABAA receptor is primarily found in the cerebellum?

α3

β2

α6 (correct)

α1

Which of the following statements about the GABAA receptor is FALSE?

It is a single subunit protein, with no splice variants. (correct)

It can be found in the lateral septum, reticular nucleus of the thalamus, and brainstem nuclei.

It can be composed of heteromeric complexes of α, β, γ, δ, and ε subunits.

It is a homomeric complex of ρ subunits in the retina.

Which of the following is a TRUE statement about the GABAB receptor?

It is insensitive to baclofen.

It is a ligand-gated ion channel.

It is activated by bicuculline.

It forms a heterodimeric complex of GABAB1 and GABAB2 subunits for function. (correct)

Which region of the brain shows expression of the α3 subunit of the GABAA receptor?

Lateral Septum Signup and view all the answers

The GABAB receptor is classified as _, while the GABAA receptor is classified as _.

metabotropic, ionotropic Signup and view all the answers

What is the primary effect of GABAB receptor activation on presynaptic GABAergic terminals?

Decreased neurotransmitter release Signup and view all the answers

Which of the following is a TRUE statement about the GABAA receptor 𝜌 subunit?

It is a component of the GABAC receptor, found in the retina. Signup and view all the answers

Which of the following is NOT a characteristic of the GABAB receptor?

It is sensitive to bicuculline. Signup and view all the answers

What is the primary effect of GABAB receptor activation on postsynaptic neurons?

Hyperpolarization Signup and view all the answers

What role does glycine play in embryonic nervous system development?

Excitatory neurotransmitter Signup and view all the answers

At what developmental stage is the K+/Cl– co-transporter KCC2 first expressed?

10 days postnatally Signup and view all the answers

How are glycine receptors influenced by external substances?

They're allosterically modulated by alcohols and anesthetics Signup and view all the answers

What condition is associated with dysregulation in glycinergic functioning?

Hereditary hyperekplexia Signup and view all the answers

Which of the following is NOT a ligand that affects glycine receptors?

Dopamine Signup and view all the answers

What is the main function of glycine in the context of GABA uptake?

It inhibits GABA uptake. Signup and view all the answers

Which of the following statements about glycine receptors is false?

Both α and β subunits contain the glycine binding site. Signup and view all the answers

Which receptor subunit type is only expressed early during development?

α2 Signup and view all the answers

What is the effect of strychnine on glycine receptors?

It inhibits them competitively. Signup and view all the answers

Which amino acid has the highest affinity for activating glycine receptors?

Glycine Signup and view all the answers

Which of the following receptors is known to be insensitive to picrotoxinin?

Receptors that contain β subunits. Signup and view all the answers

In which region of the CNS is α3 subunit primarily expressed?

The limbic system and cerebellum Signup and view all the answers

Which of the following also co-exists with glycine in some vesicles?

GABA Signup and view all the answers

What does the absence of VIAAT in certain CNS areas suggest?

The existence of other transporters. Signup and view all the answers

How are glycine receptors regulated across different developmental stages?

They are selectively regulated regionally and developmentally. Signup and view all the answers

What is a primary function of GABA in the nervous system?

Facilitates inhibitory neurotransmission Signup and view all the answers

Which compound is identified as an antagonist to glycine receptors?

Strychnine Signup and view all the answers

What occurs during GABAergic transmission after the action is initiated?

GABA is rapidly inactivated by enzymatic activity Signup and view all the answers

Which of the following describes the functional significance of glycine?

Plays a role in inhibiting spinal reflexes Signup and view all the answers

What characteristic does GABA have when discussing its synthesis and abundance?

It is derived from glutamate through specific enzymatic reactions Signup and view all the answers

In the context of performance enhancement in sports, what is the importance of strychnine?

It acts as a glycine receptor antagonist, thus increasing motor neuron activity Signup and view all the answers

Which of the following statements about GABAergic transmission is incorrect?

GABA acts as a primary excitatory neurotransmitter in the brain Signup and view all the answers

Which of the following conditions is NOT associated with a deficiency in GABA-transaminase?

Increased anxiety levels Signup and view all the answers

What is the primary effect of GABA during early developmental stages of the nervous system?

Excitation of neuronal activity through depolarization Signup and view all the answers

What is the primary function of GABA-transaminase?

Breakdown of GABA into glutamate Signup and view all the answers

How does the change in chloride ion flux in immature neurons contribute to GABA's excitatory effect?

Immature neurons have higher intracellular chloride concentrations, causing depolarization Signup and view all the answers

What does the research by Aguayo and Pancetti suggest about the role of ethanol in GABAergic neurotransmission?

Ethanol enhances GABAergic inhibition of neuronal activity Signup and view all the answers

Which of the following statements accurately describes the developmental transition of GABA's role in the nervous system?

GABA initially acts as an excitatory neurotransmitter and later transitions to an inhibitory role Signup and view all the answers

What is the most likely reason for the developmental transition of GABA's role in the nervous system?

Changes in the intracellular chloride concentration of neurons Signup and view all the answers

Which of the following is a likely consequence of GABA's excitatory role in embryonic nervous system development?

Enhanced neuronal proliferation and survival Signup and view all the answers

Study Notes

GABA & Glycine

GABA and glycine are inhibitory neurotransmitters in the adult nervous system
Ironically, the main excitatory neurotransmitter (glutamate) is the precursor to GABA
GABA is synthesized by the enzyme glutamic acid decarboxylase (GAD)
GAD (either 65 or 67) is specifically located on GABAergic neurons
GABA is present in various inhibitory interneurons and projection neurons (e.g., basket, stellate, Purkinje) throughout the brain
GABA is transported back into GABAergic terminals via dedicated GABA transporters
It is also buffered by astrocytes, where GABA is degraded by GABA-transaminase (GABA-T)
This results, in GABAergic neurotransmission, in a net flow of GABA from the neuronal to the astrocytic compartment

GABA Receptors

GABA receptors are thought to be pentameric complexes with over 2000 subunit combinations
The a1 subunit is the most prevalent in the brain
GABA receptors have differing subunit compositions, based on a1, a2, and a3 subunits localized in particular areas (e.g a1 in hippocampus, a2 in hippocampus, striatum, etc., a3 in regions complimentary to a1, also in brainstem and lateral septum)
GABA receptors also include a6 subunit primarily localized in the cerebellum
GABA receptors have various binding sites (benzodiazepine, GABA, barbiturate, steroid, picrotoxin)

Receptor Nomenclature

GABA receptors are classified as ionotropic and metabotropic based on function
Ionotropic receptors are Cl- channels
Metabotropic receptors are linked to G proteins
GABA receptors have multiple subunit complexes and are either homomeric or heteromeric
Homomeric subunits are made up of the same subunits
Heteromeric subunits are made up of combinations of different subunits
GABA receptors have different locations within the nervous system that are regionally regulated

Receptor Nomenclature: Is there a GABAC?

GABAC receptors are homomeric
They are distinct from GABAA and GABAB receptors
Activated by cis-4-aminobutan-2-enoate (CACA)
They have a considerable sequence homology with GABAA receptors
They are considered to be a pharmacologically distinct GABAA receptor subclass

Drugs Affecting GABAergic Transmission

Various drugs, acting as agonists or antagonists, affect GABAergic transmission
Benzodiazepines, barbiturates, and alcohol are agonists
Bicuculline, picrotoxin, and 3-APMPA are antagonists

Mechanism of Action for Alcohol

Alcohol modulates glycine receptors and increases the amplitude of glycine currents
Alcohol enhances GABAergic synaptic inhibition by acting on GABAA receptors

Hereditary Hyperekplexia

Characterized by increased muscle tone and exaggerated startle response, often fatal at early age
Caused mutations in the GLRA1 gene
GLRA1 gene provides instructions for making one part of the glycine receptor, leading to improperly responding glycine receptors

Glycine

Glycine is a smaller amino acid, acting as an inhibitory neurotransmitter
Synthesized from serine, by the enzyme serine hydroxymethyltransferase (SHMT)
Packaged into vesicles by a vesicular transporter
Removed from the cleft by specific glycine transporters (GLYT1 and GLYT2) located on astrocytes and presynaptic terminals
Degraded by a glycine cleavage system (GCS) in the mitochondria
Glycine receptors are pentmeric, similar to GABAA receptors

Composition of the GABAA & Distribution

The most common subunit in the brain is a1
a2 subunit is abundant where a1 is not
a3 subunit exists in complementary regions to a1
a6 subunit is mainly located in cerebellum

Glycine Receptors

Glycine receptors are ligand-gated Cl- channels
Pentameric structure similar to GABA receptors
Composed of α subunits with glycine binding sites and β subunits
Activated by glycine, β-alanine, taurine, etc
Inhibited by strychnine
Receptors containing β subunits are insensitive to picrotoxin

Glycine Receptor are Modulated by Alcohols and Other Drugs

Glycine receptors are allosterically modulated by alcohols and anesthetics like enflurane and isoflurane.
They're also affected by cocaine and other 5HT3 and NMDA ligands

Example Question L7

Picrotoxin primarily targets the GABAC receptor.

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Description

Explore the roles of GABA and glycine as inhibitory neurotransmitters in the nervous system. Understand the synthesis of GABA, its transport mechanisms, and the complexity of GABA receptor subunits. This quiz covers essential aspects of neurotransmission and brain function.