Subcellular regulation of metabotropic GABA receptors in the developing cerebellum. 2007

Rafael Luján
Departamento de Ciencias Médicas, Facultad de Medicina-CRIB, Universidad de Castilla-La Mancha, Campus Biosanitario, Albacete, Spain. Rafael.Lujan@uclm.es

Our understanding of GABAergic and glutamatergic neurotransmission in the CNS has been greatly influenced with the discovery and subsequent investigations of the metabotropic gamma-aminobutyric acid (B) (GABA(B)) receptors. These G-protein coupled receptors mediate slow inhibitory neurotransmission and are widely expressed and distributed in the cerebellum, where they play critical roles in neuronal excitability and modulation of synaptic neurotransmission. Their function is modulated by interaction with effector ion channels, notably inwardly rectifying K(+) channels and voltage-gated Ca(2+) channels. The receptors are encoded by two distinct subunits, GABA(B1) and GABA(B2), both of which are required in order to function normally in vivo, as shown in recombinant expression systems and in GABA(B1) -/- mice. The GABA(B1) and GABA(B2) subunits exhibit overlapping distributions in the cerebellar cortex, both at pre- and postsynaptic sites, during development and adulthood. They are in particular abundant in Purkinje cells prior to synaptogenesis and throughout postnatal development. Using high-resolution immunohistochemical techniques at the electron microscopic level in combination with quantitative analysis and three-dimensional reconstructions, it has recently been demonstrated that GABA(B) receptors undergo changes in localization on the surface of Purkinje cell dendrites and spines during postnatal development in association with the establishment and maturation of excitatory synapses. Due to this dynamic regulation, the highest densities of GABA(B1) and GABA(B2) subunits occur around the glutamatergic synapses between Purkinje cell spines and parallel fibre varicosities. This review highlights recent studies that have shed further light on the subcellular localization during postnatal development and the cell surface dynamics of GABA(B) receptors.

UI MeSH Term Description Entries
D009435 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. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D009474 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. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011689 Purkinje Cells The output neurons of the cerebellar cortex. Purkinje Cell,Purkinje Neuron,Purkyne Cell,Cell, Purkinje,Cell, Purkyne,Cells, Purkinje,Cells, Purkyne,Neuron, Purkinje,Neurons, Purkinje,Purkinje Neurons,Purkyne Cells
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002531 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. Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013569 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. Synapse
D018080 Receptors, GABA-B A subset of GABA RECEPTORS that signal through their interaction with HETEROTRIMERIC G-PROTEINS. Baclofen Receptors,GABA-B Receptors,Baclofen Receptor,GABA receptor rho1,GABA type B receptor, subunit 1,GABA(B)R1,GABA(B)R1 receptor,GABA(B)R1a protein,GABA(B)R1a receptor,GABA(B)R1b protein,GABA(B)R1b receptor,GABA-B Receptor,GABBR1 protein,GB1a protein,GB1b protein,GBR1B protein,Receptors, Baclofen,rho1 subunit, GABA receptor
D018698 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. Aluminum L-Glutamate,Glutamate,Potassium Glutamate,D-Glutamate,Glutamic Acid, (D)-Isomer,L-Glutamate,L-Glutamic Acid,Aluminum L Glutamate,D Glutamate,Glutamate, Potassium,L Glutamate,L Glutamic Acid,L-Glutamate, Aluminum

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