GABA is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system.
The N-methyl-D-aspartatereceptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA and kainate receptors. Depending on its subunit composition, its ligands are glutamate and glycine (or D-serine). However, the binding of the ligands is typically not sufficient to open the channel as it may be blocked by Mg2+ ions which are only removed when the neuron is sufficiently depolarized. Thus, the channel acts as a "coincidence detector" and only once both of these conditions are met, the channel opens and it allows positively charged ions (cations) to flow through the cell membrane. The NMDA receptor is thought to be very important for controlling synaptic plasticity and mediating learning and memory functions.
In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems. These signals are typically chemical messengers which bind to a receptor and produce physiological responses such as change in the electrical activity of a cell. For example, GABA, an inhibitory neurotransmitter, inhibits electrical activity of neurons by binding to GABAA receptors. There are three main ways the action of the receptor can be classified: relay of signal, amplification, or integration. Relaying sends the signal onward, amplification increases the effect of a single ligand, and integration allows the signal to be incorporated into another biochemical pathway.
The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory compound in the mature vertebrate central nervous system. There are two classes of GABA receptors: GABAA and GABAB. GABAA receptors are ligand-gated ion channels ; whereas GABAB receptors are G protein-coupled receptors, also called metabotropic receptors.
The GABAA receptor (GABAAR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Accurate regulation of GABAergic transmission through appropriate developmental processes, specificity to neural cell types, and responsiveness to activity is crucial for the proper functioning of nearly all aspects of the central nervous system (CNS). Upon opening, the GABAA receptor on the postsynaptic cell is selectively permeable to chloride ions and, to a lesser extent, bicarbonate ions.
Neuropharmacology is the study of how drugs affect function in the nervous system, and the neural mechanisms through which they influence behavior. There are two main branches of neuropharmacology: behavioral and molecular. Behavioral neuropharmacology focuses on the study of how drugs affect human behavior (neuropsychopharmacology), including the study of how drug dependence and addiction affect the human brain. Molecular neuropharmacology involves the study of neurons and their neurochemical interactions, with the overall goal of developing drugs that have beneficial effects on neurological function. Both of these fields are closely connected, since both are concerned with the interactions of neurotransmitters, neuropeptides, neurohormones, neuromodulators, enzymes, second messengers, co-transporters, ion channels, and receptor proteins in the central and peripheral nervous systems. Studying these interactions, researchers are developing drugs to treat many different neurological disorders, including pain, neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, psychological disorders, addiction, and many others.
The glycine receptor is the receptor of the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride currents. It is one of the most widely distributed inhibitory receptors in the central nervous system and has important roles in a variety of physiological processes, especially in mediating inhibitory neurotransmission in the spinal cord and brainstem.
Molecular neuroscience is a branch of neuroscience that observes concepts in molecular biology applied to the nervous systems of animals. The scope of this subject covers topics such as molecular neuroanatomy, mechanisms of molecular signaling in the nervous system, the effects of genetics and epigenetics on neuronal development, and the molecular basis for neuroplasticity and neurodegenerative diseases. As with molecular biology, molecular neuroscience is a relatively new field that is considerably dynamic.
GABAB receptors (GABABR) are G-protein coupled receptors for gamma-aminobutyric acid (GABA), therefore making them metabotropic receptors, that are linked via G-proteins to potassium channels. The changing potassium concentrations hyperpolarize the cell at the end of an action potential. The reversal potential of the GABAB-mediated IPSP is −100 mV, which is much more hyperpolarized than the GABAA IPSP. GABAB receptors are found in the central nervous system and the autonomic division of the peripheral nervous system.
The GABAA-rho receptor is a subclass of GABAA receptors composed entirely of rho (ρ) subunits. GABAA receptors including those of the ρ-subclass are ligand-gated ion channels responsible for mediating the effects of gamma-amino butyric acid (GABA), the major inhibitory neurotransmitter in the brain. The GABAA-ρ receptor, like other GABAA receptors, is expressed in many areas of the brain, but in contrast to other GABAA receptors, the GABAA-ρ receptor has especially high expression in the retina.
In neuroscience, Golgi cells are the most abundant inhibitory interneurons found within the granular layer of the cerebellum. Golgi cells can be found in the granular layer at various layers. The Golgi cell is essential for controlling the activity of the granular layer. They were first identified as inhibitory in 1964. It was also the first example of an inhibitory feedback network in which the inhibitory interneuron was identified anatomically. Golgi cells produce a wide lateral inhibition that reaches beyond the afferent synaptic field and inhibit granule cells via feedforward and feedback inhibitory loops. These cells synapse onto the dendrite of granule cells and unipolar brush cells. They receive excitatory input from mossy fibres, also synapsing on granule cells, and parallel fibers, which are long granule cell axons. Thereby this circuitry allows for feed-forward and feed-back inhibition of granule cells.
Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive disorder of the degradation pathway of the inhibitory neurotransmitter γ-aminobutyric acid, or GABA. The disorder has been identified in approximately 350 families, with a significant proportion being consanguineous families. The first case was identified in 1981 and published in a Dutch clinical chemistry journal that highlighted a number of neurological conditions such as delayed intellectual, motor, speech, and language as the most common manifestations. Later cases reported in the early 1990s began to show that hypotonia, hyporeflexia, seizures, and a nonprogressive ataxia were frequent clinical features as well.
GABA receptor antagonists are drugs that inhibit the action of GABA. In general these drugs produce stimulant and convulsant effects, and are mainly used for counteracting overdoses of sedative drugs.
A GABA receptor agonist is a drug that is an agonist for one or more of the GABA receptors, producing typically sedative effects, and may also cause other effects such as anxiolytic, anticonvulsant, and muscle relaxant effects. There are three receptors of the gamma-aminobutyric acid. The two receptors GABA-α and GABA-ρ are ion channels that are permeable to chloride ions which reduces neuronal excitability. The GABA-β receptor belongs to the class of G-Protein coupled receptors that inhibit adenylyl cyclase, therefore leading to decreased cyclic adenosine monophosphate (cAMP). GABA-α and GABA-ρ receptors produce sedative and hypnotic effects and have anti-convulsion properties. GABA-β receptors also produce sedative effects. Furthermore, they lead to changes in gene transcription.
Gamma-aminobutyric acid receptor subunit delta is a protein that in humans is encoded by the GABRD gene. In the mammalian brain, the delta (δ) subunit forms specific GABAA receptor subtypes by co-assembly leading to δ subunit containing GABAA receptors.
Reuptake inhibitors (RIs) are a type of reuptake modulators. It is a drug that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron. This leads to an increase in extracellular concentrations of the neurotransmitter and an increase in neurotransmission. Various drugs exert their psychological and physiological effects through reuptake inhibition, including many antidepressants and psychostimulants.
ROD-188 is a sedative drug that was structurally derived from the GABAA antagonist bicuculline by a team at Roche. Unlike bicuculline, ROD-188 acts as an agonist at GABAA receptors, being a positive allosteric modulator acting at a novel binding site distinct from those of benzodiazepines, barbiturates or muscimol, with its strongest effect produced at the α6β2γ2 subtype of the GABAA receptor. ROD-188 is one of a number of related compounds acting at this novel modulatory site, some of which also act at benzodiazepine receptors.
In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimuli. Some of them, like benzodiazepines or alcohol, function as psychoactive drugs. The site that an allosteric modulator binds to is not the same one to which an endogenous agonist of the receptor would bind. Modulators and agonists can both be called receptor ligands.
In pharmacology, GABAA receptor positive allosteric modulators, also known as GABAkines or GABAA receptor potentiators, are positive allosteric modulator (PAM) molecules that increase the activity of the GABAA receptor protein in the vertebrate central nervous system.
Presynaptic inhibition is a phenomenon in which an inhibitory neuron provides synaptic input to the axon of another neuron to make it less likely to fire an action potential. Presynaptic inhibition occurs when an inhibitory neurotransmitter, like GABA, acts on GABA receptors on the axon terminal. Or when endocannabinoids act as retrograde messengers by binding to presynaptic CB1 receptors, thereby indirectly modulating GABA and the excitability of dopamine neurons by reducing it and other presynaptic released neurotransmitters. Presynaptic inhibition is ubiquitous among sensory neurons.
