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.
The interfaces between T-CELLS and ANTIGEN-PRESENTING CELLS. Supramolecular organization of proteins takes place at these synapses involving various types of immune cells. Immunological synapses can have several functions including LYMPHOCYTE ACTIVATION; enhancing, balancing, or terminating signaling; or directing cytokine secretion.
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
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.
Specialized junctions between NEURONS which connect the cytoplasm of one neuron to another allowing direct passage of an ion current.
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.
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.
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.
Extensions of the nerve cell body. They are short and branched and receive stimuli from other NEURONS.
A class of ionotropic glutamate receptors characterized by their affinity for the agonist AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid).
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.
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.
The function of opposing or restraining the excitation of neurons or their target excitable cells.
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.
The most common inhibitory neurotransmitter in the central nervous system.
Long-Term Synaptic Depression
Excitatory Amino Acid Antagonists
Mossy Fibers, Hippocampal
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.
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.
Cytoskeleton specialization at the cytoplasmic side of postsynaptic membrane in SYNAPSES. It is involved in neuronal signaling and NEURONAL PLASTICITY and comprised of GLUTAMATE RECEPTORS; scaffolding molecules (e.g., PSD95, PSD93), and other proteins (e.g., CaCMKII).
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.
Vesicular Glutamate Transport Protein 1
A vesicular glutamate transporter protein that is predominately expressed in TELENCEPHALON of the BRAIN.
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.
Inhibitory Postsynaptic Potentials
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.
Receptors, Metabotropic Glutamate
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.
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.
Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.
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.
CA1 Region, Hippocampal
Microscopy, Electron, Transmission
Neurotransmitter receptors located on or near presynaptic terminals or varicosities. Presynaptic receptors which bind transmitter molecules released by the terminal itself are termed AUTORECEPTORS.
Organ Culture Techniques
Electrical responses recorded from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported.
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.
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.
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.
Green Fluorescent Proteins
Retinal Bipolar Cells
Neurons which conduct NERVE IMPULSES to the CENTRAL NERVOUS SYSTEM.
The superficial GRAY MATTER of the CEREBELLUM. It consists of two main layers, the stratum moleculare and the stratum granulosum.
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.
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.
Vesicular Inhibitory Amino Acid Transport Proteins
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.
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.
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).
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.
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.
Miniature Postsynaptic Potentials
The ten-layered nervous tissue membrane of the eye. It is continuous with the OPTIC NERVE and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the CHOROID and the inner surface with the VITREOUS BODY. The outer-most layer is pigmented, whereas the inner nine layers are transparent.
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.
Paired bodies containing mostly GRAY MATTER and forming part of the lateral wall of the THIRD VENTRICLE of the brain.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
CA3 Region, Hippocampal
Annelids of the class Hirudinea. Some species, the bloodsuckers, may become temporarily parasitic upon animals, including man. Medicinal leeches (HIRUDO MEDICINALIS) have been used therapeutically for drawing blood since ancient times.
Receptors, Kainic Acid
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.
The brain stem nucleus that receives the central input from the cochlear nerve. The cochlear nucleus is located lateral and dorsolateral to the inferior cerebellar peduncles and is functionally divided into dorsal and ventral parts. It is tonotopically organized, performs the first stage of central auditory processing, and projects (directly or indirectly) to higher auditory areas including the superior olivary nuclei, the medial geniculi, the inferior colliculi, and the auditory cortex.
Neurons whose primary neurotransmitter is GAMMA-AMINOBUTYRIC ACID.
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.
GRAY MATTER situated above the GYRUS HIPPOCAMPI. It is composed of three layers. The molecular layer is continuous with the HIPPOCAMPUS in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called GRANULE CELLS, whose AXONS pass through the polymorphic layer ending on the DENDRITES of PYRAMIDAL CELLS in the hippocampus.
Vesicular Glutamate Transport Proteins
A family of vesicular neurotransmitter transporter proteins that were originally characterized as sodium dependent inorganic phosphate cotransporters. Vesicular glutamate transport proteins sequester the excitatory neurotransmitter GLUTAMATE from the CYTOPLASM into SECRETORY VESICLES in exchange for lumenal PROTONS.
Calcium-Calmodulin-Dependent Protein Kinase Type 2
A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
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.
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 184.108.40.206.
Cannabinoid Receptor Modulators
A pathway of fibers that originates in the lateral part of the ENTORHINAL CORTEX, perforates the SUBICULUM of the HIPPOCAMPUS, and runs into the stratum moleculare of the hippocampus, where these fibers synapse with others that go to the DENTATE GYRUS where the pathway terminates. It is also known as the perforating fasciculus.
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.
Quaternary Ammonium Compounds
INTERNEURONS of the vertebrate RETINA. They integrate, modulate, and interpose a temporal domain in the visual message presented to the RETINAL GANGLION CELLS, with which they synapse in the inner plexiform layer.
Central Nervous System
Brain-Derived Neurotrophic Factor
Dose-Response Relationship, Radiation
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.
Neural Cell Adhesion Molecules
Cell adhesion molecule involved in a diverse range of contact-mediated interactions among neurons, astrocytes, oligodendrocytes, and myotubes. It is widely but transiently expressed in many tissues early in embryogenesis. Four main isoforms exist, including CD56; (ANTIGENS, CD56); but there are many other variants resulting from alternative splicing and post-translational modifications. (From Pigott & Power, The Adhesion Molecule FactsBook, 1993, pp115-119)
The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the BLOOD-BRAIN BARRIER and BLOOD-RETINAL BARRIER, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear.
An outbred strain of rats developed in 1915 by crossing several Wistar Institute white females with a wild gray male. Inbred strains have been derived from this original outbred strain, including Long-Evans cinnamon rats (RATS, INBRED LEC) and Otsuka-Long-Evans-Tokushima Fatty rats (RATS, INBRED OLETF), which are models for Wilson's disease and non-insulin dependent diabetes mellitus, respectively.
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.
Intracellular Signaling Peptides and Proteins
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Analysis of Variance
Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.
Low molecular weight, calcium binding muscle proteins. Their physiological function is possibly related to the contractile process.
Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS.
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.
Receptors, Antigen, T-Cell
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
Animals, Genetically Modified
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.
Receptor, Cannabinoid, CB1
A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
Amino Acid Transport System X-AG
A family of POTASSIUM and SODIUM-dependent acidic amino acid transporters that demonstrate a high affinity for GLUTAMIC ACID and ASPARTIC ACID. Several variants of this system are found in neuronal tissue.
Retinal Rod Photoreceptor Cells
Photosensitive afferent neurons located in the peripheral retina, with their density increases radially away from the FOVEA CENTRALIS. Being much more sensitive to light than the RETINAL CONE CELLS, the rod cells are responsible for twilight vision (at scotopic intensities) as well as peripheral vision, but provide no color discrimination.
A genus of the Ambystomatidae family. The best known species are the axolotl AMBYSTOMA MEXICANUM and the closely related tiger salamander Ambystoma tigrinum. They may retain gills and remain aquatic without developing all of the adult characteristics. However, under proper changes in the environment they metamorphose.
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.