Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included.Receptors, Presynaptic: Neurotransmitter receptors located on or near presynaptic terminals or varicosities. Presynaptic receptors which bind transmitter molecules released by the terminal itself are termed AUTORECEPTORS.Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.Excitatory Postsynaptic Potentials: Depolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during neurotransmission. Excitatory postsynaptic potentials can singly or in summation reach the trigger threshold for ACTION POTENTIALS.Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents.Neurotransmitter Agents: Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.Neural Inhibition: The function of opposing or restraining the excitation of neurons or their target excitable cells.Electric Stimulation: Use of electric potential or currents to elicit biological responses.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Neuromuscular Junction: The synapse between a neuron and a muscle.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Neuronal Plasticity: The capacity of the NERVOUS SYSTEM to change its reactivity as the result of successive activations.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Receptors, GABA-B: A subset of GABA RECEPTORS that signal through their interaction with HETEROTRIMERIC G-PROTEINS.Synaptic Membranes: Cell membranes associated with synapses. Both presynaptic and postsynaptic membranes are included along with their integral or tightly associated specializations for the release or reception of transmitters.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Nerve Endings: Branch-like terminations of NERVE FIBERS, sensory or motor NEURONS. Endings of sensory neurons are the beginnings of afferent pathway to the CENTRAL NERVOUS SYSTEM. Endings of motor neurons are the terminals of axons at the muscle cells. Nerve endings which release neurotransmitters are called PRESYNAPTIC TERMINALS.Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates.Mossy Fibers, Hippocampal: Axons of certain cells in the DENTATE GYRUS. They project to the polymorphic layer of the dentate gyrus and to the proximal dendrites of PYRAMIDAL CELLS of the HIPPOCAMPUS. These mossy fibers should not be confused with mossy fibers that are cerebellar afferents (see NERVE FIBERS).Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.Synaptophysin: A MARVEL domain-containing protein found in the presynaptic vesicles of NEURONS and NEUROENDOCRINE CELLS. It is commonly used as an immunocytochemical marker for neuroendocrine differentiation.Synapsins: A family of synaptic vesicle-associated proteins involved in the short-term regulation of NEUROTRANSMITTER release. Synapsin I, the predominant member of this family, links SYNAPTIC VESICLES to ACTIN FILAMENTS in the presynaptic nerve terminal. These interactions are modulated by the reversible PHOSPHORYLATION of synapsin I through various signal transduction pathways. The protein is also a substrate for cAMP- and CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASES. It is believed that these functional properties are also shared by synapsin II.Inhibitory Postsynaptic Potentials: Hyperpolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during NEUROTRANSMISSION. They are local changes which diminish responsiveness to excitatory signals.Baclofen: A GAMMA-AMINOBUTYRIC ACID derivative that is a specific agonist of GABA-B RECEPTORS. It is used in the treatment of MUSCLE SPASTICITY, especially that due to SPINAL CORD INJURIES. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Nerve Tissue ProteinsLong-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory.Calcium Channels, N-Type: CALCIUM CHANNELS that are concentrated in neural tissue. Omega toxins inhibit the actions of these channels by altering their voltage dependence.GABA Antagonists: Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.Synaptic Potentials: The voltages across pre- or post-SYNAPTIC MEMBRANES.Interneurons: Most generally any NEURONS which are not motor or sensory. Interneurons may also refer to neurons whose AXONS remain within a particular brain region in contrast to projection neurons, which have axons projecting to other brain regions.Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.Motor Neurons: Neurons which activate MUSCLE CELLS.Receptors, Metabotropic Glutamate: Cell surface proteins that bind glutamate and act through G-proteins to influence second messenger systems. Several types of metabotropic glutamate receptors have been cloned. They differ in pharmacology, distribution, and mechanisms of action.Miniature Postsynaptic Potentials: Postsynaptic potentials generated from a release of neurotransmitters from a presynaptic nerve terminal in the absence of an ACTION POTENTIAL. They may be m.e.p.p.s (miniature EXCITATORY POSTSYNAPTIC POTENTIALS) or m.i.p.p.s (miniature INHIBITORY POSTSYNAPTIC POTENTIALS).Pyridinium CompoundsTetrodotoxin: An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.Pyramidal Cells: Projection neurons in the CEREBRAL CORTEX and the HIPPOCAMPUS. Pyramidal cells have a pyramid-shaped soma with the apex and an apical dendrite pointed toward the pial surface and other dendrites and an axon emerging from the base. The axons may have local collaterals but also project outside their cortical region.Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other NEURONS.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).6-Cyano-7-nitroquinoxaline-2,3-dione: A potent excitatory amino acid antagonist with a preference for non-NMDA iontropic receptors. It is used primarily as a research tool.Astacoidea: A superfamily of various freshwater CRUSTACEA, in the infraorder Astacidea, comprising the crayfish. Common genera include Astacus and Procambarus. Crayfish resemble lobsters, but are usually much smaller.Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Animals, Newborn: Refers to animals in the period of time just after birth.omega-Conotoxin GVIA: A neurotoxic peptide, which is a cleavage product (VIa) of the omega-Conotoxin precursor protein contained in venom from the marine snail, CONUS geographus. It is an antagonist of CALCIUM CHANNELS, N-TYPE.Receptors, N-Methyl-D-Aspartate: A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.Neurons, Afferent: Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM.Receptors, AMPA: A class of ionotropic glutamate receptors characterized by their affinity for the agonist AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid).Brain Stem: The part of the brain that connects the CEREBRAL HEMISPHERES with the SPINAL CORD. It consists of the MESENCEPHALON; PONS; and MEDULLA OBLONGATA.Aplysia: An opisthobranch mollusk of the order Anaspidea. It is used frequently in studies of nervous system development because of its large identifiable neurons. Aplysiatoxin and its derivatives are not biosynthesized by Aplysia, but acquired by ingestion of Lyngbya (seaweed) species.Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.GABA Agonists: Endogenous compounds and drugs that bind to and activate GAMMA-AMINOBUTYRIC ACID receptors (RECEPTORS, GABA).Autoreceptors: Transmitter receptors on or near presynaptic terminals (or varicosities) which are sensitive to the transmitter(s) released by the terminal itself. Receptors for the hormones released by hormone-releasing cells are also included.Vesicular Glutamate Transport Protein 1: A vesicular glutamate transporter protein that is predominately expressed in TELENCEPHALON of the BRAIN.Phosphinic Acids: Inorganic or organic derivatives of phosphinic acid, H2PO(OH). They include phosphinates and phosphinic acid esters.Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.GABA-B Receptor Antagonists: Drugs that bind to but do not activate GABA-B RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-B RECEPTOR AGONISTS.Calcium Channels, Q-Type: CALCIUM CHANNELS located in the neurons of the brain.Receptors, Glutamate: Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells. Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ion channels, and metabotropic receptors which act through second messenger systems. Glutamate receptors are the most common mediators of fast excitatory synaptic transmission in the central nervous system. They have also been implicated in the mechanisms of memory and of many diseases.Calcium Channels, P-Type: CALCIUM CHANNELS located within the PURKINJE CELLS of the cerebellum. They are involved in stimulation-secretion coupling of neurons.Receptors, Kainic Acid: A class of ionotropic glutamate receptors characterized by their affinity for KAINIC ACID.Purkinje Cells: The output neurons of the cerebellar cortex.GABA-B Receptor Agonists: Endogenous compounds and drugs that bind to and activate GABA-B RECEPTORS.Spider Venoms: Venoms of arthropods of the order Araneida of the ARACHNIDA. The venoms usually contain several protein fractions, including ENZYMES, hemolytic, neurolytic, and other TOXINS, BIOLOGICAL.Long-Term Synaptic Depression: A persistent activity-dependent decrease in synaptic efficacy between NEURONS. It typically occurs following repeated low-frequency afferent stimulation, but it can be induced by other methods. Long-term depression appears to play a role in MEMORY.Organ Culture Techniques: A technique for maintenance or growth of animal organs in vitro. It refers to three-dimensional cultures of undisaggregated tissue retaining some or all of the histological features of the tissue in vivo. (Freshney, Culture of Animal Cells, 3d ed, p1)Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Cerebellum: The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.Models, Neurological: Theoretical representations that simulate the behavior or activity of the neurological system, processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Dopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Spinal Cord: A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.Afferent Pathways: Nerve structures through which impulses are conducted from a peripheral part toward a nerve center.Acetylcholine: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Receptors, GABA-A: Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.Decapodiformes: A superorder of CEPHALOPODS comprised of squid, cuttlefish, and their relatives. Their distinguishing feature is the modification of their fourth pair of arms into tentacles, resulting in 10 limbs.Quinoxalines2-Amino-5-phosphonovalerate: The D-enantiomer is a potent and specific antagonist of NMDA glutamate receptors (RECEPTORS, N-METHYL-D-ASPARTATE). The L form is inactive at NMDA receptors but may affect the AP4 (2-amino-4-phosphonobutyrate; APB) excitatory amino acid receptors.Neocortex: The largest portion of the CEREBRAL CORTEX in which the NEURONS are arranged in six layers in the mammalian brain: molecular, external granular, external pyramidal, internal granular, internal pyramidal and multiform layers.omega-Agatoxin IVA: A neuropeptide toxin from the venom of the funnel web spider, Agelenopsis aperta. It inhibits CALCIUM CHANNELS, P-TYPE by altering the voltage-dependent gating so that very large depolarizations are needed for channel opening. It also inhibits CALCIUM CHANNELS, Q-TYPE.Bicuculline: An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.H-Reflex: A monosynaptic reflex elicited by stimulating a nerve, particularly the tibial nerve, with an electric shock.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Lampreys: Common name for the only family (Petromyzontidae) of eellike fish in the order Petromyzontiformes. They are jawless but have a sucking mouth with horny teeth.Synaptotagmins: A family of vesicular transport proteins characterized by an N-terminal transmembrane region and two C-terminal calcium-binding domains.Vesicular Inhibitory Amino Acid Transport Proteins: A family of vesicular neurotransmitter transporter proteins that sequester the inhibitory neurotransmitters GLYCINE; GAMMA-AMINOBUTYRIC ACID; and possibly GAMMA-HYDROXYBUTYRATE into SECRETORY VESICLES.rab3A GTP-Binding Protein: The most abundant member of the RAB3 GTP-BINDING PROTEINS. It is involved in calcium-dependent EXOCYTOSIS and is localized to neurons and neuroendocrine cells. This enzyme was formerly listed as EC 18.104.22.168.Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.Neural Pathways: Neural tracts connecting one part of the nervous system with another.Excitatory Amino Acid Agents: Drugs used for their actions on any aspect of excitatory amino acid neurotransmitter systems. Included are drugs that act on excitatory amino acid receptors, affect the life cycle of excitatory amino acid transmitters, or affect the survival of neurons using excitatory amino acids.Corpus Striatum: Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.Synaptosomal-Associated Protein 25: A ubiquitous target SNARE protein that interacts with SYNTAXIN and SYNAPTOBREVIN. It is a core component of the machinery for intracellular MEMBRANE FUSION. The sequence contains 2 SNARE domains, one is the prototype for the Qb-SNARES, and the other is the prototype for the Qc-SNARES.Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.Ganglia, Invertebrate: Clusters of neuronal cell bodies in invertebrates. Invertebrate ganglia may also contain neuronal processes and non-neuronal supporting cells. Many invertebrate ganglia are favorable subjects for research because they have small numbers of functional neuronal types which can be identified from one animal to another.Aminobutyrates: Derivatives of BUTYRIC ACID that contain one or more amino groups attached to the aliphatic structure. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the aminobutryrate structure.Goldfish: Common name for Carassius auratus, a type of carp (CARPS).Cannabinoid Receptor Modulators: Compounds that interact with and modulate the activity of CANNABINOID RECEPTORS.Receptors, Neurotransmitter: Cell surface receptors that bind signalling molecules released by neurons and convert these signals into intracellular changes influencing the behavior of cells. Neurotransmitter is used here in its most general sense, including not only messengers that act to regulate ion channels, but also those which act on second messenger systems and those which may act at a distance from their release sites. Included are receptors for neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not located at synapses.Receptor, Cannabinoid, CB1: A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of ERECTILE DYSFUNCTION.Fluorescent Dyes: Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Mice, Inbred C57BLNerve Fibers: Slender processes of NEURONS, including the AXONS and their glial envelopes (MYELIN SHEATH). Nerve fibers conduct nerve impulses to and from the CENTRAL NERVOUS SYSTEM.Neuropeptides: Peptides released by NEURONS as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells.Receptors, GABA: Cell-surface proteins that bind GAMMA-AMINOBUTYRIC ACID with high affinity and trigger changes that influence the behavior of cells. GABA-A receptors control chloride channels formed by the receptor complex itself. They are blocked by bicuculline and usually have modulatory sites sensitive to benzodiazepines and barbiturates. GABA-B receptors act through G-proteins on several effector systems, are insensitive to bicuculline, and have a high affinity for L-baclofen.Cerebral Cortex: The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.GABA-A Receptor Antagonists: Drugs that bind to but do not activate GABA-A RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-A RECEPTOR AGONISTS.Aldicarb: Carbamate derivative used as an insecticide, acaricide, and nematocide.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.4-Aminopyridine: One of the POTASSIUM CHANNEL BLOCKERS, with secondary effect on calcium currents, which is used mainly as a research tool and to characterize channel subtypes.alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid: An IBOTENIC ACID homolog and glutamate agonist. The compound is the defining agonist for the AMPA subtype of glutamate receptors (RECEPTORS, AMPA). It has been used as a radionuclide imaging agent but is more commonly used as an experimental tool in cell biological studies.Quaternary Ammonium Compounds: Derivatives of ammonium compounds, NH4+ Y-, in which all four of the hydrogens bonded to nitrogen have been replaced with hydrocarbyl groups. These are distinguished from IMINES which are RN=CR2.CA3 Region, Hippocampal: A subsection of the hippocampus, described by Lorente de No, that is located between the HIPPOCAMPUS CA2 FIELD and the DENTATE GYRUS.Sodium Channel Blockers: A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.N-Methylaspartate: An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Green Fluorescent Proteins: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.Ganglia, Parasympathetic: Ganglia of the parasympathetic nervous system, including the ciliary, pterygopalatine, submandibular, and otic ganglia in the cranial region and intrinsic (terminal) ganglia associated with target organs in the thorax and abdomen.Picrotoxin: A noncompetitive antagonist at GABA-A receptors and thus a convulsant. Picrotoxin blocks the GAMMA-AMINOBUTYRIC ACID-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates.Retinal Bipolar Cells: INTERNEURONS of the vertebrate RETINA containing two processes. They receive inputs from the RETINAL PHOTORECEPTOR CELLS and send outputs to the RETINAL GANGLION CELLS. The bipolar cells also make lateral connections in the retina with the RETINAL HORIZONTAL CELLS and with the AMACRINE CELLS.Kainic Acid: (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose.GABAergic Neurons: Neurons whose primary neurotransmitter is GAMMA-AMINOBUTYRIC ACID.Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized CONNECTIVE TISSUE located outside the CENTRAL NERVOUS SYSTEM.Cerebellar Cortex: The superficial GRAY MATTER of the CEREBELLUM. It consists of two main layers, the stratum moleculare and the stratum granulosum.Animals, Genetically Modified: ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring.Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.Egtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.Vesicle-Associated Membrane Protein 2: A synaptic membrane protein involved in MEMBRANE FUSION of SYNAPTIC VESICLES with the presynaptic membranes. It is the prototype member of the R-SNARE PROTEINS.Posterior Horn Cells: Neurons in the SPINAL CORD DORSAL HORN whose cell bodies and processes are confined entirely to the CENTRAL NERVOUS SYSTEM. They receive collateral or direct terminations of dorsal root fibers. They send their axons either directly to ANTERIOR HORN CELLS or to the WHITE MATTER ascending and descending longitudinal fibers.Nerve Net: A meshlike structure composed of interconnecting nerve cells that are separated at the synaptic junction or joined to one another by cytoplasmic processes. In invertebrates, for example, the nerve net allows nerve impulses to spread over a wide area of the net because synapses can pass information in any direction.Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.Receptors, Nicotinic: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.Motor Endplate: The specialized postsynaptic region of a muscle cell. The motor endplate is immediately across the synaptic cleft from the presynaptic axon terminal. Among its anatomical specializations are junctional folds which harbor a high density of cholinergic receptors.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Ganglia, Sympathetic: Ganglia of the sympathetic nervous system including the paravertebral and the prevertebral ganglia. Among these are the sympathetic chain ganglia, the superior, middle, and inferior cervical ganglia, and the aorticorenal, celiac, and stellate ganglia.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Chelating Agents: Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS.Endocannabinoids: Fatty acid derivatives that have specificity for CANNABINOID RECEPTORS. They are structurally distinct from CANNABINOIDS and were originally discovered as a group of endogenous CANNABINOID RECEPTOR AGONISTS.Glutamate Decarboxylase: A pyridoxal-phosphate protein that catalyzes the alpha-decarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining GAMMA-AMINOBUTYRIC ACID levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC 22.214.171.124.Microscopy, Electron, Transmission: Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.CyclopropanesMice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.omega-Conotoxins: A family of structurally related neurotoxic peptides from mollusk venom that inhibit voltage-activated entry of calcium into the presynaptic membrane. They selectively inhibit N-, P-, and Q-type calcium channels.Vesicular Glutamate Transport Protein 2: A vesicular glutamate transporter protein that is predominately expressed in the DIENCEPHALON and lower brainstem regions of the CENTRAL NERVOUS SYSTEM.Benzoxazines: OXAZINES with a fused BENZENE ring.Potassium: An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.Receptors, Dopamine D2: A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.GABA Agents: Substances used for their pharmacological actions on GABAergic systems. GABAergic agents include agonists, antagonists, degradation or uptake inhibitors, depleters, precursors, and modulators of receptor function.Clonidine: An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.Benzothiadiazines: Heterocyclic compounds of a ring with SULFUR and two NITROGEN atoms fused to a BENZENE ring. Members inhibit SODIUM-POTASSIUM-CHLORIDE SYMPORTERS and are used as DIURETICS.Cycloleucine: An amino acid formed by cyclization of leucine. It has cytostatic, immunosuppressive and antineoplastic activities.Axonal Transport: The directed transport of ORGANELLES and molecules along nerve cell AXONS. Transport can be anterograde (from the cell body) or retrograde (toward the cell body). (Alberts et al., Molecular Biology of the Cell, 3d ed, pG3)Receptors, Adrenergic, alpha-2: A subclass of alpha-adrenergic receptors found on both presynaptic and postsynaptic membranes where they signal through Gi-Go G-PROTEINS. While postsynaptic alpha-2 receptors play a traditional role in mediating the effects of ADRENERGIC AGONISTS, the subset of alpha-2 receptors found on presynaptic membranes signal the feedback inhibition of NEUROTRANSMITTER release.Adenosine: A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.CA1 Region, Hippocampal: One of four subsections of the hippocampus described by Lorente de No, located furthest from the DENTATE GYRUS.Piperidines: A family of hexahydropyridines.Synaptotagmin I: A vesicular transport protein expressed predominately in NEURONS. Synaptotagmin helps regulate EXOCYTOSIS of SYNAPTIC VESICLES and appears to serve as a calcium sensor to trigger NEUROTRANSMITTER release. It also acts as a nerve cell receptor for certain BOTULINUM TOXINS.Neostriatum: The phylogenetically newer part of the CORPUS STRIATUM consisting of the CAUDATE NUCLEUS and PUTAMEN. It is often called simply the striatum.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Auditory Pathways: NEURAL PATHWAYS and connections within the CENTRAL NERVOUS SYSTEM, beginning at the hair cells of the ORGAN OF CORTI, continuing along the eighth cranial nerve, and terminating at the AUDITORY CORTEX.Receptors, Adrenergic: Cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction.Calcium Channels, R-Type: CALCIUM CHANNELS located in the neurons of the brain. They are inhibited by the marine snail toxin, omega conotoxin MVIIC.Xanthenes: Compounds with three aromatic rings in linear arrangement with an OXYGEN in the center ring.Receptors, Cannabinoid: A class of G-protein-coupled receptors that are specific for CANNABINOIDS such as those derived from CANNABIS. They also bind a structurally distinct class of endogenous factors referred to as ENDOCANNABINOIDS. The receptor class may play a role in modulating the release of signaling molecules such as NEUROTRANSMITTERS and CYTOKINES.Superior Cervical Ganglion: The largest and uppermost of the paravertebral sympathetic ganglia.Stellate Ganglion: A paravertebral sympathetic ganglion formed by the fusion of the inferior cervical and first thoracic ganglia.Iontophoresis: Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ION EXCHANGE; AIR IONIZATION nor PHONOPHORESIS, none of which requires current.Receptors, Cholinergic: Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology.Cell Adhesion Molecules, Neuronal: Surface ligands that mediate cell-to-cell adhesion and function in the assembly and interconnection of the vertebrate nervous system. These molecules promote cell adhesion via a homophilic mechanism. These are not to be confused with NEURAL CELL ADHESION MOLECULES, now known to be expressed in a variety of tissues and cell types in addition to nervous tissue.Naphthalenes: Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.Cats: The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)Brain-Derived Neurotrophic Factor: A member of the nerve growth factor family of trophic factors. In the brain BDNF has a trophic action on retinal, cholinergic, and dopaminergic neurons, and in the peripheral nervous system it acts on both motor and sensory neurons. (From Kendrew, The Encyclopedia of Molecular Biology, 1994)Glycine Agents: Substances used for their pharmacological actions on glycinergic systems. Glycinergic agents include agonists, antagonists, degradation or uptake inhibitors, depleters, precursors, and modulators of receptor function.Receptors, Adrenergic, alpha: One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.Curare: Plant extracts from several species, including genera STRYCHNOS and Chondodendron, which contain TETRAHYDROISOQUINOLINES that produce PARALYSIS of skeletal muscle. These extracts are toxic and must be used with the administration of artificial respiration.Elapid Venoms: Venoms from snakes of the family Elapidae, including cobras, kraits, mambas, coral, tiger, and Australian snakes. The venoms contain polypeptide toxins of various kinds, cytolytic, hemolytic, and neurotoxic factors, but fewer enzymes than viper or crotalid venoms. Many of the toxins have been characterized.Dendritic Spines: Spiny processes on DENDRITES, each of which receives excitatory input from one nerve ending (NERVE ENDINGS). They are commonly found on PURKINJE CELLS and PYRAMIDAL CELLS.Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.Receptors, Purinergic P1: A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra).Electric Conductivity: The ability of a substrate to allow the passage of ELECTRONS.Larva: Wormlike or grublike stage, following the egg in the life cycle of insects, worms, and other metamorphosing animals.Microscopy, Immunoelectron: Microscopy in which the samples are first stained immunocytochemically and then examined using an electron microscope. Immunoelectron microscopy is used extensively in diagnostic virology as part of very sensitive immunoassays.Tetany: A disorder characterized by muscle twitches, cramps, and carpopedal spasm, and when severe, laryngospasm and seizures. This condition is associated with unstable depolarization of axonal membranes, primarily in the peripheral nervous system. Tetany usually results from HYPOCALCEMIA or reduced serum levels of MAGNESIUM that may be associated with HYPERVENTILATION; HYPOPARATHYROIDISM; RICKETS; UREMIA; or other conditions. (From Adams et al., Principles of Neurology, 6th ed, p1490)Syntaxin 1: A neuronal cell membrane protein that combines with SNAP-25 and SYNAPTOBREVIN 2 to form a SNARE complex that leads to EXOCYTOSIS.Receptor, Adenosine A1: A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of tissues including the BRAIN and DORSAL HORN NEURONS. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.Biophysics: The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.Reflex, Monosynaptic: A reflex in which the AFFERENT NEURONS synapse directly on the EFFERENT NEURONS, without any INTERCALATED NEURONS. (Lockard, Desk Reference for Neuroscience, 2nd ed.)Cadmium Chloride: A cadmium halide in the form of colorless crystals, soluble in water, methanol, and ethanol. It is used in photography, in dyeing, and calico printing, and as a solution to precipitate sulfides. (McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Nicotinic Antagonists: Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.Bungarotoxins: Neurotoxic proteins from the venom of the banded or Formosan krait (Bungarus multicinctus, an elapid snake). alpha-Bungarotoxin blocks nicotinic acetylcholine receptors and has been used to isolate and study them; beta- and gamma-bungarotoxins act presynaptically causing acetylcholine release and depletion. Both alpha and beta forms have been characterized, the alpha being similar to the large, long or Type II neurotoxins from other elapid venoms.rab3 GTP-Binding Proteins: A genetically related subfamily of RAB GTP-BINDING PROTEINS involved in calcium-dependent EXOCYTOSIS. This enzyme was formerly listed as EC 126.96.36.199.