Neuroscience Chapter on GABA and Glycine

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system (CNS). It plays a crucial role in regulating neuronal excitability and is involved in various functions, including sleep, mood, and anxiety.

GABA is synthesized from glutamate by the enzyme glutamic acid decarboxylase (GAD). It is abundant in the brain and spinal cord, particularly in the basal ganglia, hippocampus, and cerebellum.

GABA exerts its effects by binding to specific receptors on the surface of neurons. There are two main types of GABA receptors: GABA-A receptors and GABA-B receptors.

Glycine is another major inhibitory neurotransmitter in the CNS. It is particularly important in mediating spinal reflexes and motor control.

Glycine is synthesized from serine by the enzyme serine hydroxymethyltransferase. It is abundant in the spinal cord and brainstem.

Glycine interacts with its receptors to inhibit neuronal activity. Glycine receptors are located on the postsynaptic membrane and are ionotropic, meaning they directly control the flow of ions.

Glycine acts as an excitatory neurotransmitter in the developing nervous system, contributing to neuronal depolarization. This occurs before the expression of the K+/Cl- co-transporter KCC2, which later shifts the chloride reversal potential, making glycine inhibitory.

The K+/Cl- co-transporter KCC2, crucial for establishing inhibitory signaling by glycine, becomes active around 10 days after birth in rodents. Its expression leads to a negative shift in the Cl- reversal potential, transforming glycine's action from excitatory to inhibitory.

Alcohols and anesthetics like enflurane and isoflurane, along with cocaine and certain 5HT3 and NMDAR ligands, modulate the function of glycine receptors. These substances bind to the receptor, influencing its activity without directly interacting with the glycine binding site.

A rare genetic condition called hereditary hyperekplexia is caused by impairments in glycinergic neurotransmission. It results in exaggerated startle reflexes and muscle stiffness due to decreased inhibitory action of glycine.

β mRNA is commonly found in the central nervous system (CNS), but it doesn't form glycine receptors on its own. This suggests that additional components or processes are likely required for the formation of functional glycine receptors.

A family of receptors that respond to the neurotransmitter GABA. They are ionotropic and are composed of five protein subunits that assemble to form a chloride channel.

A family of receptors that are metabotropic. They are activated by baclofen and are not blocked by bicuculline. They are composed of two protein subunits: GABAB1 and GABAB2.

The α1 subunit of the GABAA receptor is concentrated in key brain regions related to learning and memory, including the hippocampus, amygdala, and cortex.

The α3 subunit of the GABAA receptor is expressed in brain regions complementary to the α1 subunit, including the lateral septum, reticular nucleus of the thalamus, and brainstem nuclei.

The α6 subunit of the GABAA receptor is uniquely concentrated in the cerebellum, a brain region crucial for motor coordination and learning.

There are 19 different subunits that make up GABAA receptors, and they can be grouped into eight families.

GABAA receptors are composed of five subunits that assemble together to form a chloride channel.

GABAB receptors can be found both on postsynaptic neurons and on presynaptic terminals.

The GABAB receptor is a metabotropic receptor that is coupled to G-protein pathways.

Glycine and GABA are neurotransmitters that can be co-released by certain neurons, activating specific receptors in the synapse.

In the central nervous system (CNS), some areas rich in GABA and/or glycine lack the VIAAT transporter, suggesting the presence of other transporters.

Glycine receptors are believed to have a pentameric structure, similar to GABAA, nicotinic cholinergic, and 5HT3 receptors.

Glycine receptors are composed of α (four subunits) and β (single type) subunits, with only α subunits containing the glycine binding site.

Glycine receptors can be formed by α subunits alone or in combination with β subunits.

Glycine receptors are activated by various ligands in descending order of potency: glycine > β-alanine > taurine > L- and D-alanine > L-serine >> D-serine.

Glycine receptors can be inhibited by strychnine, a competitive inhibitor, or picrotoxin, a non-competitive inhibitor.

Glycine receptors containing β subunits are insensitive to picrotoxinin, a potent convulsant.

Different α subunits of glycine receptors exhibit distinct developmental and regional expression patterns.

α1 subunit corresponds to strychnine-sensitive sites in adults, while α2 is expressed early in development and throughout the CNS, but mainly in specific areas in adults. α3 is found in limbic system and cerebellum, and α4 is not detected in adult humans.

GABAergic neurons are nerve cells that use GABA as their primary neurotransmitter. These neurons are involved in various brain functions, including anxiety, sleep, and movement.

GABA Receptors are protein complexes found on the surface of neurons. They bind to GABA, triggering changes in the neuron's electrical activity. Different types of GABA receptors exist, each with its own specific function.

In GABA-T deficiency, the body cannot effectively break down GABA. This leads to an excess of GABA, resulting in various neurological symptoms.

Individuals with GABA-T deficiency may experience various neurological symptoms, including seizures, uncontrolled movements, exaggerated reflexes, muscle weakness, and excessive sleepiness.

GABA is involved in various neuropsychiatric conditions, such as epilepsy, Huntington's disease, and alcohol addiction. Its role in these conditions is complex, often related to imbalances in its activity.

In the embryonic nervous system, GABA exhibits excitatory properties. It depolarizes neurons, promoting cell growth and development. This is unlike its typical inhibitory function in mature brains.

This switch from excitatory to inhibitory function of GABA is due to changes in chloride ion (Cl-) transport across neuronal membranes. These changes are crucial for proper brain development and function.

Ethanol, the active ingredient in alcoholic beverages, affects GABA signaling. It enhances the inhibitory effects of GABA, contributing to its sedative and intoxicating effects.

GABA plays a crucial role in regulating sleep. GABAergic neurons in the brain promote sleep by inhibiting neuronal activity in areas involved in wakefulness.