Evidence for Two Subpopulations of Cerebrospinal Fluid-Contacting Neurons with Opposite GABAergic Signaling in Adult Mouse Spinal Cord.

Spinal cerebrospinal fluid-contacting neurons (CSF-cNs) form an evolutionary conserved bipolar cell population localized around the central canal of all vertebrates. CSF-cNs were shown to express molecular markers of neuronal immaturity into adulthood; however, the impact of their incomplete maturation on the chloride (Cl) homeostasis as well as GABAergic signaling remains unknown. Using adult mice from both sexes, in situ hybridization revealed that a proportion of spinal CSF-cNs (18.

Glial Endozepines Reverse High-Fat Diet-Induced Obesity by Enhancing Hypothalamic Response to Peripheral Leptin.

Research on energy homeostasis has focused on neuronal signaling; however, the role of glial cells has remained little explored. Glial endozepines exert anorexigenic actions by mechanisms which remain poorly understood. In this context, the present study was designed to decipher the mechanisms underlying the anorexigenic action of endozepines and to investigate their potential curative effect on high-fat diet-induced obesity.

GABA receptors modulate Ca but not G protein-gated inwardly rectifying K channels in cerebrospinal-fluid contacting neurones of mouse brainstem.

Key Points: Medullo-spinal CSF contacting neurones (CSF-cNs) located around the central canal are conserved in all vertebrates and suggested to be a novel sensory system intrinsic to the CNS. CSF-cNs receive GABAergic inhibitory synaptic inputs involving ionotropic GABA receptors, but the contribution of metabotropic GABA receptors (GABA -Rs) has not yet been studied. Here, we indicate that CSF-cNs express functional GABA -Rs that inhibit postsynaptic calcium channels but fail to activate inhibitory potassium channel of the Kir3-type.

KCTD Hetero-oligomers Confer Unique Kinetic Properties on Hippocampal GABAB Receptor-Induced K+ Currents.

Unlabelled: GABA receptors are the G-protein coupled receptors for the main inhibitory neurotransmitter in the brain, GABA. GABA receptors were shown to associate with homo-oligomers of auxiliary KCTD8, KCTD12, KCTD12b, and KCTD16 subunits (named after their T1 K-channel tetramerization domain) that regulate G-protein signaling of the receptor. Here we provide evidence that GABA receptors also associate with hetero-oligomers of KCTD subunits.

A single polycystic kidney disease 2-like 1 channel opening acts as a spike generator in cerebrospinal fluid-contacting neurons of adult mouse brainstem.

Cerebrospinal fluid contacting neurons (CSF-cNs) are found around the central canal of all vertebrates. They present a typical morphology, with a single dendrite that projects into the cavity and ends in the CSF with a protuberance. These anatomical features have led to the suggestion that CSF-cNs might have sensory functions, either by sensing CSF movement or composition, but the physiological mechanisms for any such role are unknown.

Up-regulation of GABA(B) receptor signaling by constitutive assembly with the K+ channel tetramerization domain-containing protein 12 (KCTD12).

GABA(B) receptors are the G-protein coupled receptors (GPCRs) for GABA, the main inhibitory neurotransmitter in the central nervous system. Native GABA(B) receptors comprise principle and auxiliary subunits that regulate receptor properties in distinct ways. The principle subunits GABA(B1a), GABA(B1b), and GABA(B2) form fully functional heteromeric GABA(B(1a,2)) and GABA(B(1b,2)) receptors.

Opposite effects of KCTD subunit domains on GABA(B) receptor-mediated desensitization.

GABA(B) receptors assemble from principle and auxiliary subunits. The principle subunits GABA(B1) and GABA(B2) form functional heteromeric GABA(B(1,2)) receptors that associate with homotetramers of auxiliary KCTD8, -12, -12b, or -16 (named after their K(+) channel tetramerization domain) subunits. These auxiliary subunits constitute receptor subtypes with distinct functional properties.

GABAB receptors: physiological functions and mechanisms of diversity.

GABA(B) receptors are the G-protein-coupled receptors (GPCRs) for gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the central nervous system. GABA(B) receptors are implicated in the etiology of a variety of psychiatric disorders and are considered attractive drug targets. With the cloning of GABA(B) receptor subunits 13 years ago, substantial progress was made in the understanding of the molecular structure, physiology, and pharmacology of these receptors.

NMDA receptor-dependent GABAB receptor internalization via CaMKII phosphorylation of serine 867 in GABAB1.

GABAB receptors are the G-protein-coupled receptors for GABA, the main inhibitory neurotransmitter in the brain. GABAB receptors are abundant on dendritic spines, where they dampen postsynaptic excitability and inhibit Ca2+ influx through NMDA receptors when activated by spillover of GABA from neighboring GABAergic terminals. Here, we show that an excitatory signaling cascade enables spines to counteract this GABAB-mediated inhibition.

Native GABA(B) receptors are heteromultimers with a family of auxiliary subunits.

GABA(B) receptors are the G-protein-coupled receptors for gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. They are expressed in almost all neurons of the brain, where they regulate synaptic transmission and signal propagation by controlling the activity of voltage-gated calcium (Ca(v)) and inward-rectifier potassium (K(ir)) channels. Molecular cloning revealed that functional GABA(B) receptors are formed by the heteromeric assembly of GABA(B1) with GABA(B2) subunits.

A mouse model for visualization of GABA(B) receptors.

GABA(B) receptors are the G-protein-coupled receptors for the neurotransmitter gamma-aminobutyric acid (GABA). Receptor subtypes are based on the subunit isoforms GABA(B1a) and GABA(B1b), which combine with GABA(B2) subunits to form heteromeric receptors. Here, we used a modified bacterial artificial chromosome (BAC) containing the GABA(B1) gene to generate transgenic mice expressing GABA(B1a) and GABA(B1b) subunits fused to the enhanced green fluorescence protein (eGFP).

The GABAB1a isoform mediates heterosynaptic depression at hippocampal mossy fiber synapses.

GABA(B) receptor subtypes are based on the subunit isoforms GABA(B1a) and GABA(B1b), which associate with GABA(B2) subunits to form pharmacologically indistinguishable GABA(B(1a,2)) and GABA(B(1b,2)) receptors. Studies with mice selectively expressing GABA(B1a) or GABA(B1b) subunits revealed that GABA(B(1a,2)) receptors are more abundant than GABA(B(1b,2)) receptors at glutamatergic terminals. Accordingly, it was found that GABA(B(1a,2)) receptors are more efficient than GABA(B(1b,2)) receptors in inhibiting glutamate release when maximally activated by exogenous application of the agonist baclofen.

Synapse loss in cortex of agrin-deficient mice after genetic rescue of perinatal death.

Agrin-deficient mice die at birth because of aberrant development of the neuromuscular junctions. Here, we examined the role of agrin at brain synapses. We show that agrin is associated with excitatory but not inhibitory synapses in the cerebral cortex.

Corelease of GABA/glycine in lamina-X of the spinal cord of neonatal rats.

Spinal-cord slices from neonatal rats were used to record lamina-X neurons using the patch-clamp technique under whole cell recording configuration. Lamina-X surrounds the central canal of the spinal cord and contains sympathetic preganglionic neurons of the central autonomic nucleus. Miniature inhibitory postsynaptic currents were recorded in the presence of tetrodotoxin and kynurenic acid to block action potential-dependent transmitter release and glutamatergic transmissions, respectively.

Modulation of GABAergic synaptic transmission by terminal nicotinic acetylcholine receptors in the central autonomic nucleus of the neonatal rat spinal cord.

Using patch clamp recordings from an in vitro spinal cord slice preparation of neonatal rats (9-15days old), we characterized the GABAergic synaptic transmission in sympathetic preganglionic neurones (SPN) of the central autonomic nucleus (CA) of lamina X. Local applications of isoguvacine (100microM), a selective agonist at GABA(A) receptors, induced in all cells tested a chloride current which was abolished by bicuculline, a competitive antagonist at GABA(A) receptors. In addition, 25% of the recorded cells displayed spontaneous tetrodotoxin-insensitive and bicuculline-sensitive chloride miniature inhibitory postsynaptic currents (mIPSCs).

The rat spinal cord slice: Its use in generating pharmacological evidence for cholinergic transmission using the alpha7 subtype of nicotinic receptors in the central autonomic nucleus.

Lamina X surrounds the central canal of the spinal cord and is an important site for the convergence of somatic and visceral afferent inputs relaying nociceptive information. Lamina X contains sympathetic preganglionic neurons (SPN) in the so-called central autonomic nucleus which may participate to viscero-autonomic reflexes. Here, we describe a transversal slice preparation of postnatal rat thoracolumbar spinal cord which allows the detailed characterization of the morphology, electrophysiological properties, synaptic activities and receptor pharmacology of neurons surrounding the central canal.

Choline induces Ca2+ entry in cultured sympathetic neurones isolated from rat superior cervical ganglion.

Choline has been shown to be a specific agonist at alpha7 nicotinic acetylcholine receptors, which are the most Ca(2+) permeable of the ionotropic receptor channels. Whole-cell patch recording combined with the measurement of intracellular free Ca(2+) concentration ([Ca(2+)](i), using Indo1, in cultured rat superior cervical ganglion neurones demonstrated that application of choline induced a slowly desensitizing inward current and increased [Ca(2+)](i). The effect was dose dependent with an EC(50) of 1.