Neuroscience
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The command and control of limb movements by the cerebellar and reflex pathways are modeled by means of a circuit whose structure is deduced from functional constraints. One constraint is that fast limb movements must be accurate although they cannot be continuously controlled in closed loop by use of sensory signals. Thus, the pathways which process the motor orders must contain approximate inverse functions of the bio-mechanical functions of the limb and of the muscles. ⋯ Reflexes comparable to the myotatic and tendinous reflexes, and stabilizing reactions comparable to the cerebellar sensory-motor reactions, reduce efficiently the effects of perturbing torques. These results allow to link the behavioral concepts of the equilibrium-point "lambda model" [J Motor Behav 18 (1986) 17] with anatomical and physiological features: gains of reflexes and sensori-motor reactions set the slope of the "invariant characteristic," and efferent copies set the "threshold of the stretch reflex." Thus, mathematical and physical laws account for the raison d'etre of the inhibitory nature of Purkinje cells and for the conspicuous anatomical pattern of the cerebellar pathways. These properties of these pathways allow to perform approximate inverse calculations after learning of direct functions, and insure also the coordination of voluntary and reflex motor orders.
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Etomidate (ET), an imidazole general anesthetic, has been medically widely used. Recent evidence suggests that the inhibitory neurotransmitter GABA receptor may be one of the important molecular target(s) of general anesthetics. Up to date, little attention has been directed toward the sacral dorsal commissural nucleus (SDCN), which serves as a relay of sensory information from the pelvic viscera in the spinal cord. ⋯ At lower concentrations (0.1-100 microM), ET reversibly potentiated GABA (1 microM)-activated Cl(-) currents in a bell-shaped manner, with the maximal facilitative effect at 10 microM, whereas at concentrations >100 microM, the peak of the ET-induced current was suppressed in the absence or presence of GABA (1 microM). These results suggest that in SDCN, in addition to the potentiation of GABA(A) receptor-mediated responses at low concentrations and the direct activation of GABA(A) receptors at moderate concentrations as expected, ET produced a fast blocking action at high concentrations. The general anesthetic-induced effects in SDCN, at least the potentiation of GABA responses, may significantly contribute to anesthesia of pelvic viscera during the general anesthesia.
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Comparative Study
Developmental emergence of hippocampal fast-field "ripple" oscillations in the behaving rat pups.
Sharp wave and associated fast oscillatory ripples (140-200 Hz) in the cornu ammonis 1 region are the most synchronous hippocampal patterns in the adult rat. Spike sequences associated with sharp waves are believed to play a critical role in transferring transient memories from the hippocampus to the neocortex and the emergence of superfast ripples is pathognostic in temporal lobe epilepsy. Sharp waves in cornu ammonis 1 stratum radiatum are induced by a strong depolarization by the cornu ammonis 3 Schaffer collaterals, due to the synchronous discharge of cornu ammonis 3 pyramidal cells. ⋯ Once ripples emerged, the intra-ripple frequency assumed adult values. The developmental time course of the ripple parallels the switch in the GABA(A) receptor-mediated signaling from excitation to inhibition. The time course may also reflect hitherto unidentified emergence of neuronal gap junctions.
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Comparative Study
Synaptic and subcellular localization of A-kinase anchoring protein 150 in rat hippocampal CA1 pyramidal cells: Co-localization with excitatory synaptic markers.
Excitatory and inhibitory ionotropic receptors are regulated by protein kinases and phosphatases, which are localized to specific subcellular locations by one of several anchoring proteins. One of these is the A-kinase anchoring protein (AKAP150), which confers spatial specificity to protein kinase A and protein phosphatase 2B in the rat brain. The distribution of AKAP150 was examined at rat hippocampal CA1 pyramidal cell asymmetric and symmetric post-synaptic densities and with respect to the distribution of markers of excitatory (vesicular glutamate transporter 1, glutamate receptor subunit 1) and inhibitory receptors (vesicular GABA transporter, GABA receptor type A beta2/3 subunits, gephyrin) and the Golgi marker, trans-Golgi network glycoprotein 38. ⋯ In contrast, we did not find AKAP150-immunoreactivity associated with inhibitory synapses in rat CA1 neurons, despite reports demonstrating an in vitro interaction between AKAP150 and GABA receptor type A receptor beta subunits, and the reported co-localization of these proteins in rat hippocampal cultures. There was some overlap between AKAP150 and GABA receptor type A receptor beta2/3-immunoreactivity intracellularly in perinuclear clusters. These findings support previous work indicating the integration of kinase and phosphatase activity at excitatory synapses by AKAP150, but do not support a role for selective targeting of AKAP150 and its accompanying proteins to inhibitory synapses.
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Comparative Study
Neuronal gap junctions in the mouse main olfactory bulb: morphological analyses on transgenic mice.
In the present study we analyzed the structural features of extraglomerular gap junction-forming processes in mouse olfactory bulb electron microscopically. This work complements a previous study in which we analyzed the structural features of neuronal gap junction-forming processes within the glomerulus itself. Furthermore we examined connexin 36 expressing cells in the mouse olfactory bulb by analyzing transgenic mice in which the connexin 36 coding sequence was replaced with histological reporters. ⋯ Multiple immunofluorescent labelings further revealed that presumed interneurons expressing connexin 36 in the periglomerular region rarely expressed calbindin, calretinin or tyrosine hydroxylase and are likely to comprise a chemically uncharacterized class of neurons. Similarly, interneurons expressing connexin 36 in the granule cell layer were rarely positive for calretinin, which was expressed in numerous presumed granule cells in the mouse main olfactory bulb. In summary, these findings revealed that mitral/tufted cells make gap junctions with diverse types of neurons; in the glomeruli gap junction-forming interneuronal processes originated from some types of periglomerular cells but others from a hitherto uncharacterized neuron type(s), and in the extraglomerular region gap-junction forming processes originate mainly from a subset of cells within the granule cell layer.