Neuroscience
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Comparative Study
Effect of early isolation on signal transfer in the entorhinal cortex-dentate-hippocampal system.
Deprivation of socio-sensory interactions during early life impairs brain function in adulthood. In previous investigations we showed that early isolation severely affects neuron development in several structures of the hippocampal region, including the entorhinal cortex. In the present study we investigated the effects of early isolation on signal processing along the entorhinal cortex-dentate-CA3-CA1 system, a major memory circuit of the hippocampal region. ⋯ While the entorhinal cortex was moderately impaired, the dentate-hippocampal system was more severely affected. The impairment in the signal transfer along the entorhinal cortex-dentate gyrus-CA3-CA1 system was heavier in males, confirming the larger susceptibility of this sex to early experience. This work provides evidence that malfunctioning of a major hippocampal network may underlie the learning deficits induced by impoverished surroundings during early life.
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A number of rat neuropathy models have been developed to simulate human neuropathic pain conditions, such as spontaneous pain, hyperalgesia, and allodynia. In the present study, to determine the relative importance of injury site (proximal or distal to the primary afferent neurons) and injury type (motor or sensory), we examined pain-related behaviors and changes of brain-derived neurotrophic factor expression in the dorsal root ganglion in sham-operated rats, and in the L5 dorsal rhizotomy, L5 ventral rhizotomy, L5 dorsal rhizotomy+ventral rhizotomy, and L5 spinal nerve transection models. ⋯ On the other hand, L5 spinal nerve transection, but not dorsal rhizotomy, dorsal rhizotomy+ventral rhizotomy or ventral rhizotomy, increased the expression of brain-derived neurotrophic factor in the L4 dorsal root ganglion at 7 days after surgery. Taken together, these findings suggest that the upregulation of brain-derived neurotrophic factor expression in the L4 and L5 dorsal root ganglion neurons may be, at least in part, involved in the pathophysiological mechanisms of neuropathic pain and that the selective nerve root injury models may be useful for studying the underlying mechanisms of chronic pain after nerve injury.
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Dopamine released from lateral efferent fibers modulates the activity of the auditory nerve, but the signaling mechanism by which this is mediated is not known. The present study investigated the signal transduction pathway for the dopamine D1 receptor in the guinea-pig cochlea. D1 receptor immunolabeling was localized to the spiral ganglia neurons and at the base of the inner hair cells. ⋯ Furthermore, it was found that the level of glutamate receptor 1 phosphorylation at the protein kinase A site (Ser845) was increased by the D1 agonist, but decreased by D1 antagonist. Our results provide evidence that the D1 receptor is localized in the spiral ganglion neurons as well as the nerve endings under the inner hair cells and they can modulate auditory nerve function. One signal transduction pathway of D1 receptor in the auditory nerve is via protein kinase A-mediated glutamate receptor 1 phosphorylation.
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Activity of the immediate early genes c-fos and zif268 was compared across hemispheres in rats with unilateral, excitotoxic lesions of the hippocampus (dentate gyrus and CA fields 1-4). Counts of the protein products of these genes were made shortly after rats performed a test of spatial working memory in the radial-arm maze, a task that is sensitive to bilateral lesions of the hippocampus. Unilateral hippocampal lesions produced evidence of widespread hypoactivity. ⋯ In contrast, no observable changes were detected in the anterior cingulate, infralimbic or prelimbic cortices, as well as several amygdala nuclei, even though many of these regions receive projections from the subiculum. Instead, the immediate early gene changes were closely linked to sites that are thought to be required for successful task performance, with both immediate early genes giving similar patterns of results. The findings support the notion that the anterior thalamic nuclei, hippocampus, and parahippocampal cortices form the key components of an interdependent neuronal network involved in spatial mnemonic processing.
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Several findings suggest that glucocorticoid hormones influence the propensity of an individual to develop cocaine abuse. These hormones activate two related transcription factors, the glucocorticoid receptor and the mineralocorticoid receptor. We have shown previously that mice carrying a mutation of the glucocorticoid receptor gene specifically in neural cells, glucocorticoid receptor knock-out in the brain, show a dramatic decrease in cocaine-induced self-administration and no behavioral sensitization to this drug, two experimental procedures considered relevant models of addiction. ⋯ However, cocaine-induced changes in the levels of these mRNAs were not modified in glucocorticoid receptor knock-out in the brain mice. In contrast, mutant mice showed altered response in mRNA levels of N-methyl-D-aspartate, GLUR5 and GLUR6 glutamate receptor subunits as well as of enkephalin following cocaine administration. These modifications may be associated to decrease of behavioral effects of cocaine observed in glucocorticoid receptor knock-out in the brain mice.