Neuroscience
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Recent in vivo electrophysiological studies suggest that chronic dopamine depletion alters profoundly the firing pattern of basal ganglia neurons. These changes may disrupt the processing of cortical information flow from the striatum to the output nuclei, and presumably underlie the clinical manifestations of Parkinson's disease. We have recently reported that chronic nigrostriatal lesions induce changes in the functional state of striatal medium-spiny neurons (MSNs) that could facilitate spreading of cortical synchronous activity (approximately 1 Hz) to striatal target nuclei. ⋯ Following systemic administration of SKF38393 or SKF81279 the membrane potential of striatal MSNs was upheld into a more hyperpolarized value and action potential firing probability decreased. D1 agonists also increased the latency to the cortically driven plateau depolarization and reduced the peak potential of the short latency depolarizing postsynaptic response to a more hyperpolarized value. The present study provides in vivo evidence indicating that pharmacological stimulation of D1-class dopamine receptors can modulate the flow of cortical information through the striatum in the parkinsonian state.
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It has been shown that the noradrenergic (NE) locus coeruleus (LC)-hippocampal pathway plays an important role in learning and memory processing, and that the development of this transmitter pathway is influenced by neurotrophic factors. Although some of these factors have been discovered, the regulatory mechanisms for this developmental event have not been fully elucidated. Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor influencing LC-NE neurons. ⋯ NE fiber innervation into the hippocampal co-transplant from an adjacent brainstem graft was also influenced by the presence of GDNF, with a significantly more robust innervation observed in transplants from wildtype fetuses. The most successful LC/hippocampal co-grafts were generated from fetuses expressing the wildtype GDNF background, whereas the most severely affected transplants were derived from double transplants from null-mutated fetuses. Our data suggest that development of the NE LC-hippocampal pathway is dependent on the presence of GDNF, most likely through a target-derived neurotrophic function.
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Bidirectional modifications in synaptic efficacy are central components in recent models of cortical learning and memory, and we previously demonstrated both long-term synaptic potentiation (LTP) and long-term synaptic depression (LTD) in the neocortex of the unanaesthetized adult rat. Here, we have examined the effects of N-methyl-D-aspartate receptor (NMDAR) blockade on the induction of LTD, LTP, and depotentiation of field potentials evoked in sensorimotor cortex by stimulation of the white matter in the adult, freely moving rat. High frequency (300 Hz) stimulation (HFS) was used to induce LTP and prolonged, low-frequency (1 Hz) stimulation was used to induce either depotentiation or LTD. ⋯ Under NMDAR blockade, HFS failed to induce LTP and instead produced a depression effect similar to LTD. Following washout of the drug, HFS induced a normal LTP effect. Unlike LTP, LTD and depotentiation were found to be NMDAR-independent in the neocortex of the freely moving rat.
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Comparative Study
Corticotropin-releasing factor receptor type 1 and 2 mRNA expression in the rat anterior pituitary is modulated by intermittent hypoxia, cold and restraint.
We had previously demonstrated that continual-hypoxia stimulated corticotropin-releasing factor (CRF)mRNA in hypothalamus, and release of CRF, as well as enhancing plasma adrenocorticotropic-hormone and corticosterone of rats. The present study demonstrates using in situ autoradiography that CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2) mRNA in the rat anterior pituitary is changed by intermittent hypoxia, cold, restraint, alone and in combination. Rats were exposed to intermittent hypoxia for 4 h/day during various periods in a hypobaric chamber. ⋯ These results show that the acute response to intermittent hypoxia is a decrease in the CRF receptor mRNA whereas longer exposure to the three environmental stressors hypoxia, cold and restraint is needed to provoke an increase. This may have important consequences for adaptation to high altitude. The significant differences between the expression of CRFR1 mRNA and CRFR2 mRNA in response to the different stimuli might suggest that the two receptors in the pituitary play different roles in behavior.
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Low glutathione levels have been observed in the prefrontal cortex and the cerebrospinal fluid of schizophrenic patients, possibly enhancing the cerebral susceptibility to oxidative stress. We used osteogenic disorder Shionogi mutant rats, which constitute an adequate model of the human redox regulation because both are unable to synthesize ascorbic acid. To study the long-term consequences of a glutathione deficit, we treated developing rats with L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of glutathione synthesis, and later investigated their behavior until adulthood. ⋯ Inhibition of brain glutathione synthesis and dopamine uptake in developing rats induce long-term cognitive deficits occurring in adulthood. Males are affected earlier and more intensively than females, at least concerning object recognition. The present study suggests that the low glutathione levels observed in schizophrenic patients may participate in the development of some of their cognitive deficits.