Neuroscience
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Interactions between the intracellular domain of ligand-gated membrane receptors and cytoplasmic proteins play important roles in their assembly, clustering, and function. In addition, protein-protein interactions may provide an alternative mechanism by which neurotransmitters activate intracellular pathways. In this study, we report a novel interaction between the GABA rho1 subunit and cellular retinoic acid binding protein in mammalian retina that could serve as a link between the GABA signaling pathway and the control of gene expression in neurons. ⋯ In the absence of the rho1 receptor, these cells showed enhanced neurite outgrowth when exposed to retinoic acid and GABA had no effect on their response to retinoic acid. In contrast, cells stably transfected with the human rho1 subunit showed a significantly reduced sensitivity to retinoic acid when exposed to GABA. These results suggest that the GABA receptor subunit effectively altered gene expression through its interaction with the cellular retinoic acid binding protein pathway.
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Comparative Study
Rapid damping of food-entrained circadian rhythm of clock gene expression in clock-defective peripheral tissues under fasting conditions.
Restricted feeding-induced free-running oscillation of clock genes in the liver was studied in homozygous Clock-mutant (Clock/Clock) mice. Similar to wild-type mice, Clock/Clock mice showed robust food-anticipatory behavioral activity in accordance with a restricted feeding schedule. ⋯ However, during the fasting days after temporal feeding cues were removed, the oscillation of clock genes in the liver and heart, excluding the suprachiasmatic nuclei, appeared to result in arrhythmicity in Clock/Clock mice. Thus, although the CLOCK-based molecular mechanism is not required for the expression of food-anticipatory activity, intact CLOCK protein might be involved in sustaining several cycles of peripheral circadian oscillations after restricted feeding-induced resetting.
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Cocaine self-administration experiments were designed to assess the respective roles of D1-like and D2-like dopamine receptors in the ventral forebrain in cocaine reinforcement. D1-like or D2-like dopamine receptor antagonists were microinjected into the nucleus accumbens core, nucleus accumbens shell, neostriatum or lateral septum prior to sessions in which cocaine was self-administered under a progressive ratio schedule by rats. ⋯ Neither SCH-23390 nor eticlopride influenced cocaine reinforcement when administered into the neostriatum or lateral septum. Collectively, these results indicate that D1-like and D2 dopamine receptors in the nucleus accumbens shell selectively modulate the reinforcing efficacy of cocaine, whereas D1-like and D2 dopamine receptors in the accumbens core have a more general influence on reinforced behaviors.
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Globular bushy cells are a key element of brainstem circuits that mediate the early stages of sound localization. Many of their physiological properties have been attributed to convergence of inputs from the auditory nerve, many of which are large with complex geometry, but the number of these terminals contacting individual cells has not been measured directly. Herein we report, using cats as the experimental model, that this number ranged greatly (9-69) across a population of 12 cells, but over one-half of the cells (seven of 12) received between 15 and 23 inputs. ⋯ This predictive model reveals that basic physiological features, such as precise first spike latencies and peristimulus time histogram shapes, including primary-like with notch and onset-L, can be generated in these cells without including inhibitory inputs. However, phase-locking is not significantly enhanced over auditory-nerve fibers. These combined anatomical and computational approaches reveal additional parameters, such as active zone density, nerve terminal size, numbers and sources of inhibitory inputs and their activity patterns, that must be determined and incorporated into next-generation models to understand the physiology of globular bushy cells.
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Comparative Study
Electrophysiological properties and thermosensitivity of mouse preoptic and anterior hypothalamic neurons in culture.
Responses of mouse preoptic and anterior hypothalamic neurons to variations of temperature are key elements in regulating the setpoint of homeotherms. The goal of the present work was to assess the relevance of culture preparations for investigating the cellular mechanisms underlying thermosensitivity in hypothalamic cells. Our working hypothesis was that some of the main properties of preoptic/anterior hypothalamic neurons in culture are similar to those reported by other authors in slice preparations. ⋯ The increased firing rate of warm-sensitive cells in response to warming can be prepotential and/or synaptically driven. Overall, our data suggest that a warm-sensitive phenotype is already developed in cultured cells. Therefore, and despite obvious differences in their networks, cultured and slice preparations of hypothalamic neurons can complement each other for further studies of warm-sensitivity at the cellular and molecular level.