Neuroscience
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Exposure to organophosphorus nerve agents induces brain seizures, which can cause profound brain damage resulting in death or long-term cognitive deficits. The amygdala and the hippocampus are two of the most seizure-prone brain structures, but their relative contribution to the generation of seizures after nerve agent exposure is unclear. Here, we report that application of 1 muM soman for 30 min, in rat coronal brain slices containing both the hippocampus and the amygdala, produces prolonged synchronous neuronal discharges (10-40 s duration, 1.5-5 min interval of occurrence) resembling ictal activity in the basolateral nucleus of the amygdala (BLA), but only interictal-like activity ("spikes" of 100-250 ms duration; 2-5 s interval) in the pyramidal cell layer of the CA1 hippocampal area. ⋯ The GluR5KR antagonist UBP302 reduced the amplitude of the hippocampal interictal-like spikes, and eliminated the seizure-like discharges in the BLA, or reduced their duration and frequency, with no significant effect on the evoked field potentials. This is the first study reporting in vitro ictal-like activity in response to a nerve agent. Our findings, along with previous literature, suggest that the amygdala may play a more important role than the hippocampus in the generation of seizures following soman exposure, and provide the first evidence that GluR5KR antagonists may be an effective treatment against nerve agent-induced seizures.
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Prenatal and neonatal exposure to relatively low-dose bisphenol-A (BPA, 20 microg/kg/day) causes hyper-locomotion of male rat offspring. This research investigated the developmental pattern of activity-dependent synaptic plasticity in dorsolateral (DL) striatum, a cellular basis for motor controlling, in male rat offspring with hyper-locomotion. High frequency stimulation (four-pulse bursts at 100 Hz) was undertaken to induce long-term potentiation (LTP) and long-term depression (LTD) in corticostriatal synapse during postnatal day (PD) 10-32. ⋯ Furthermore, the dopamine 2 receptor (D2R) agonist quinpirole recovered the LTD induction in PD28 BPA-rats, which was D1R-dependent and metabotropic glutamate receptor-dependent. In PD28 control rats, the blockade of D2R by l-sulpiride reversed the D1R- and mGluR-dependent LTD to short-term potentiation. Therefore, the findings provide functional evidence that prenatal and neonatal exposure to low-dose BPA causes deficits in development of LTP and LTD at DL-striatum via altering the function of dopaminergic receptors.
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Neurogenesis in the adult dentate gyrus (DG) of the hippocampus has been implicated in neural plasticity and cognition but the specific functions contributed by adult-born neurons remain controversial. Here, we have explored the relationship between adult hippocampal neurogenesis and memory function using tasks which specifically require the participation of the DG. In two separate experiments several groups of rats were exposed to fractionated ionizing radiation (two sessions of 7 Gy each on consecutive days) applied either to the whole brain or focally, aiming at a region overlying the hippocampus. ⋯ In the second experiment, focal irradiation reduced DCX expression by 36% but did not impair performance on (1) a standard non-matching-to-place (NMTP) task, (2) a more demanding NMTP task with increasingly longer within-trial delays, (3) a long-term retention test of the alternation rule and (4) a spatial reversal task. However, rats irradiated focally showed clear deficits in a "purely" contextual fear-conditioning task at short and long retention intervals. These data demonstrate that reduced adult hippocampal neurogenesis produces marked deficits in the rapid acquisition of emotionally relevant contextual information but spares spatial working memory function, the long-term retention of acquired spatial rules and the ability to flexibly modify learned spatial strategies.
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Autonomic dysreflexia is a potentially life-threatening hypertensive syndrome following high thoracic (T) spinal cord injury (SCI). It is commonly triggered by noxious pelvic stimuli below the injury site that correlates with increased sprouting of primary afferent C-fibers into the lumbosacral (L/S) spinal cord. We have recently demonstrated that injury-induced plasticity of (L/S) propriospinal neurons, which relay pelvic visceral sensations to thoracolumbar sympathetic preganglionic neurons, is also correlated with the development of this syndrome. ⋯ Quantitative analysis showed that the density of CGRP(+) afferent fibers was significantly increased in the L/S dorsal horns of T4-transected versus sham rats, whereas RT97(+) afferent fiber density showed no change. Importantly, CTb-labeled pelvic afferent fibers were co-localized with CGRP(+) fibers, but not with RT97(+) fibers. These results suggest that the sprouting of unmyelinated nociceptive pelvic afferents following high thoracic SCI, but not myelinated fibers, contributes to hypertensive autonomic dysreflexia induced by pelvic visceral pain.
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Olfactory bulbectomy (OBX) in rats causes several behavioral and neurochemical changes. However, the extent and onset of physiological and behavioral changes induced after bulbectomy have been little examined. ⋯ Removal of the olfactory bulbs results in rapid, stable and persistent changes in basal locomotor activity, body temperature, heart rate and heart rate variability. Although the sleep-wake cycle of these parameters is not altered, increases in circadian amplitude are apparent within 3 days after surgery. This indicates that physiological changes in the OBX rat are the immediate result of olfactory bulb removal. Further, stress responsivity in OBX rats depends on stressor intensity. Bulbectomized rats display smaller temperature and heart rate responses to less intense witness stress compared with sham rats. Increased locomotor responses to more intense novel cage stress are present in the home cage as well as the open field. The present study shows that olfactory bulbectomy has rapid and persistent influence on basal and stress-induced physiological parameters.