Neurotransmitters: GABA and Glycine

gamma-aminobutyric acid (GABA), a neurotransmitter found in the brain, is synthesized from glutamate. GABA is involved in reducing neuronal activity, promoting relaxation, and inhibiting anxiety.

Glycine is an amino acid that acts as a neurotransmitter in the spinal cord and brainstem. It is involved in inhibiting motor neuron activity and regulating muscle movement.

GABA receptors are protein complexes found on neurons that bind to GABA. They are classified into GABA-A and GABA-B receptors, each with distinct actions.

Strychnine is a potent antagonist of glycine receptors. It blocks the inhibitory effects of glycine, leading to increased muscle activity and potentially fatal convulsions.

Glycine receptors are protein complexes found in the spinal cord and brainstem that bind to glycine. They are involved in inhibiting motor neuron activity.

GABAergic transmission refers to the process of communication between neurons using GABA as the neurotransmitter. GABA is released from presynaptic neurons and binds to GABA receptors on postsynaptic neurons.

Glycinergic transmission refers to the process of communication between neurons using glycine as the neurotransmitter. Glycine is released from presynaptic neurons and binds to glycine receptors on postsynaptic neurons.

The inactivation of GABA action occurs through reuptake mechanisms, where GABA is transported back into presynaptic neurons, or through enzymatic breakdown by GABA transaminase.

GABA is a neurotransmitter involved in various brain functions and plays a role in several neuropsychiatric disorders like epilepsy, Huntington's disease, tardive dyskinesia, addiction, and sleep disorders.

GABA-T deficiency is a rare genetic disorder that leads to a buildup of GABA in the body, causing severe symptoms such as seizures, uncontrolled movements, and developmental delays. This deficiency is due to a lack of the enzyme GABA-T, which is responsible for breaking down GABA.

In the early stages of development, the nervous system utilizes GABA as an excitatory neurotransmitter. Unlike in mature neurons where it usually inhibits, in developing neurons, GABA depolarizes the membrane, causing an influx of chloride ions. This excitatory effect is believed to be crucial for the development of the central nervous system.

GABA's primary function in adult neurons is inhibition, meaning it reduces the activity of other neurons. This inhibitory action is crucial for controlling neuronal firing and regulating brain activity.

Glycine receptors, like GABA-A receptors, are structured as a pentamer, consisting of five subunits. They are similar in structure to other ion channels, like nicotinic acetylcholine receptors and serotonin 5HT3 receptors.

Glycine receptors primarily contain two types of subunits: alpha (α) and beta (β). There are four different α subunits and only one type of β subunit. The α subunits are responsible for binding glycine.

Glycine receptors can be formed by only α subunits or in combination with β subunits. The presence of β subunits makes the receptor insensitive to a drug called picrotoxinin.

Glycine receptors are activated by several different molecules. They are most strongly activated by glycine, followed by β-alanine, taurine, L- and D-alanine, and L-serine. D-serine activates the receptors to a lesser extent.

Glycine receptors can be inhibited by two different mechanisms. They can be inhibited competitively by strychnine, meaning strychnine blocks the binding of glycine. Alternatively, they can be non-competitively inhibited by picrotoxin, which prevents the receptor from opening even if glycine is bound.

Glycine receptors are regulated throughout the lifespan and vary in their distribution in the central nervous system (CNS). α1 subunits are associated with strychnine-sensitive sites in adults. α2 subunits are expressed early in development and are found widely in the CNS but only in a few places in adults. α3 subunits are found in parts of the limbic system and the cerebellum. α4 subunits have not been detected in adult humans.

The distribution of glycine receptors in the brain is a complex, changing landscape. The expression of different α subunits is regulated during development, making glycine receptors very dynamic.

Glycine receptors play a crucial role in inhibitory neurotransmission, particularly in the spinal cord. They are important in controlling muscle movement and regulating reflexes. Their activation leads to the opening of chloride channels, which hyperpolarizes the postsynaptic neuron, reducing its firing rate.

Glycine acts as an excitatory neurotransmitter in the developing nervous system.

The K+/Cl– co-transporter KCC2, expressed after 10 days postnatally, shifts the Cl– reversal potential negatively, contributing to the change in glycine's action from excitatory to inhibitory.

Glycine receptors are influenced by various substances, including alcohols, anesthetics, cocaine, and certain serotonin and NMDA receptor ligands.

Alcohol affects the central nervous system by modulating glycine receptors, along with GABA receptors. This modulation can lead to changes in behavior and cognitive function.

Hereditary hyperekplexia is a genetic disorder caused by a deficiency in glycine neurotransmission, leading to an exaggerated startle response and muscle stiffness.

β-mRNA is present in the central nervous system but does not independently form glycine receptors.

Glycinergic synapses become active early in brain development, contributing to neuronal activity in embryonic and immature stages.

Glycine, like GABA, can depolarize neurons in developing organisms, influencing their activity during critical stages of nervous system development.

Infants with hyperekplexia display increased muscle tone, making them stiff and inflexible.

A sudden, involuntary muscle contraction triggered by unexpected stimuli, like loud noises, in infants with hyperekplexia.

The brief period following a startle response where infants become rigid, unable to move, and may even stop breathing.

A rare symptom of hyperekplexia where infants exhibit involuntary muscle twitches as they fall asleep.

A characteristic response of infants with hyperekplexia where tapping their nose causes head extension and muscle spasms.

Recurrent seizures or epilepsy can sometimes occur in infants with hyperekplexia.

The symptoms of hyperekplexia generally lessen and often resolve by the age of 1.

A type of ionotropic receptor that binds to glutamate, contributing to fast excitatory neurotransmission. Found widely in the brain, facilitating various functions like learning and memory.

A type of ionotropic receptor that binds to glutamate, plays a vital role in synaptic plasticity (learning and memory) and is activated by N-methyl-d-aspartate (NMDA).