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Excitatory Activity (excitatory + activity)
Selected AbstractsInhibition of neural activity depletes orexin from rat hypothalamic slice cultureJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2010Shotaro Michinaga Abstract Orexins (hypocretins) are neuropeptides produced by a small population of hypothalamic neurons whose dysregulation may lead to narcolepsy, a neurological disorder characterized by disorganization of sleep and wakefulness. Excessive stimulation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors causes preferential loss of orexin neurons in the hypothalamus, whereas an adequate level of neuronal excitatory activities is generally known to be important for the maintenance of central neurons. By examining the effect of manipulation of neural activity, we found that 24,72 hr application of tetrodotoxin (TTX) caused a substantial decrease in the number of orexin-immunoreactive neurons, but not of melanin-concentrating hormone-immunoreactive neurons, in hypothalamic slice culture. Similar results were obtained when neural activity was arrested by added extracellular Mg2+. Reduction of orexin expression by TTX and Mg2+ was also observed at mRNA level. The decrease of orexin-immunoreactive neurons was attributable to depletion of orexin, because it was reversible after washout of TTX or elevated extracellular Mg2+ and was not associated with induction of cell death. Blockers of voltage-dependent Ca2+ channels as well as of NMDA receptors also induced a significant and selective decrease of orexin-immunoreactive neurons. Moreover, TTX-induced decrease of orexin immunoreactivity was largely abrogated by concurrent application of a moderate concentration of NMDA. These results suggest that Ca2+ entry associated with nontoxic levels of spontaneous activity of glutamatergic inputs plays an important role in the maintenance of orexin neurons in a tissue culture model. © 2009 Wiley-Liss, Inc. [source] Quantitative effects produced by modifications of neuronal activity on the size of GABAA receptor clusters in hippocampal slice culturesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2004Serge Marty Abstract The number and strength of GABAergic synapses needs to be precisely adjusted for adequate control of excitatory activity. We investigated to what extent the size of GABAA receptor clusters at inhibitory synapses is under the regulation of neuronal activity. Slices from P7 rat hippocampus were cultured for 13 days in the presence of bicuculline or 4-aminopyridine (4-AP) to increase neuronal activity, or DNQX to decrease activity. The changes provoked by these treatments on clusters immunoreactive for the ,1 and ,2 subunits of the GABAA receptor or gephyrin were quantitatively evaluated. While an increase in activity augmented the density of these clusters, a decrease in activity provoked, in contrast, a decrease in their density. An inverse regulation was observed for the size of individual clusters. Bicuculline and 4-AP decreased whilst DNQX increased the mean size of the clusters. When the pharmacological treatments were applied for 2 days instead of 2 weeks, no effects on the size of the clusters were observed. The variations in the mean size of individual clusters were mainly due to changes in the number of small clusters. Finally, a regulation of the size of GABAA receptor clusters occurred during development in vivo, with a decrease of the mean size of the clusters between P7 and P21. This physiological change was also the result of an increase in the number of small clusters. These results indicate that neuronal activity regulates the mean size of GABAA receptor- and gephyrin-immunoreactive clusters by modifying specifically the number of synapses with small clusters of receptors. [source] Levodopa treatment reverses endocannabinoid system abnormalities in experimental parkinsonismJOURNAL OF NEUROCHEMISTRY, Issue 4 2003Mauro Maccarrone Abstract Cannabinoid receptors and their endogenous ligands are potent inhibitors of neurotransmitter release in the brain. Here, we show that in a rat model of Parkinson's disease induced by unilateral nigral lesion with 6-hydroxydopamine (6-OHDA), the striatal levels of the endocannabinoid anandamide (AEA) were increased, while the activity of its membrane transporter and hydrolase (fatty-acid amide hydrolase, FAAH) were decreased. These changes were not observed in the cerebellum of the same animals. Moreover, the frequency and amplitude of glutamate-mediated spontaneous excitatory post-synaptic currents were augmented in striatal spiny neurones recorded from parkinsonian rats. Remarkably, the anomalies in the endocannabinoid system, as well as those in glutamatergic activity, were completely reversed by chronic treatment of parkinsonian rats with levodopa, and the pharmacological inhibition of FAAH restored a normal glutamatergic activity in 6-OHDA-lesioned animals. Thus, the increased striatal levels of AEA may reflect a compensatory mechanism trying to counteract the abnormal corticostriatal glutamatergic drive in parkinsonian rats. However, this mechanism seems to be unsuccessful, since spontaneous excitatory activity is still higher in these animals. Taken together, these data show that anomalies in the endocannabinoid system induced by experimental parkinsonism are restricted to the striatum and can be reversed by chronic levodopa treatment, and suggest that inhibition of FAAH might represent a possible target to decrease the abnormal cortical glutamatergic drive in Parkinson's disease. [source] ,-Aminobutyric acid is present in a spatially discrete subpopulation of hair cells in the crista ampullaris of the toadfish Opsanus tauTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 1 2004Gay R. Holstein Abstract Although ,-aminobutyric acid (GABA) and glutamate are known to be present in the vestibular sensory epithelia of a variety of species, the functional relationship between these two transmitters is not clear. The present study addresses the three-dimensional spatial distribution of GABA and glutamate immunoreactivity in the vestibular labyrinth of the oyster toadfish by using whole end organs labeled by immunofluorescence with monoclonal anti-GABA and/or antiglutamate antibodies and visualized as whole mounts by multiphoton confocal microscopy. We find glutamate-immunoreactive hair cells present throughout the sensory epithelium. In contrast, prominent GABA immunoreactivity is restricted to a small population of hair cells located in the central region of the crista. Double immunofluorescence reveals two distinct staining patterns in GABA-labeled hair cells. Most (,80%) GABA-labeled cells show trace levels of glutamate, appropriate for the metabolic/synthetic role of cytoplasmic glutamate. The remainder of the GABA-stained cells contain substantial levels of both GABA and glutamate, suggesting transmitter colocalization. In the toadfish utricle, glutamatergic hair cells are present throughout the macula. GABA-immunoreactive hair cells follow the arc of the striola, and most GABA-labeled receptor cells coexpress glutamate. The localization of GABA was explored in other species as well. In the pigeon, GABAergic hair cells are present throughout the crista ampullaris. Our findings demonstrate that multiple, neurochemically distinct types of hair cells are present in vestibular sensory epithelia. These observations, together with the excitatory activity generally associated with 8th nerve afferent fibers, strongly suggest that GABA serves an important, specific, and complex role in determining primary afferent response dynamics. J. Comp. Neurol. 471:1,10, 2004. © 2004 Wiley-Liss, Inc. [source] | ||||||||||