Neuroscience
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Botulinum neurotoxin serotype A (BoNT/A) acts by cleaving synaptosome-associated-protein-25 (SNAP-25) in nerve terminals to inhibit neuronal release and shows long-lasting antinociceptive action in neuropathic pain. However, its precise mechanism of action remains unclear. Our study aimed to characterize BoNT/A-induced neuroimmunological changes after chronic constriction injury (CCI) of the sciatic nerve. ⋯ BoNT/A also diminished the injury-induced upregulation of SNAP-25 expression in both structures. We provide evidence that BoNT/A impedes injury-activated neuronal function in structures distant from the injection site, which is demonstrated by its influence on NOS1, prodynorphin and pronociceptin mRNA levels in the DRG. Moreover, the silence of microglia/macrophages after BoNT/A administration could be secondary to the inhibition of neuronal activity, but this decrease in neuroimmune interactions could be the key to the long-lasting BoNT/A effect on neuropathic pain.
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The present study intended to investigate the involvement of dopaminergic and glutamatergic systems of the basolateral amygdala in amnesia induced by the stimulation of dorsal hippocampal cannabinoid receptors in male Wistar rats. The animals were stereotaxically implanted with guide cannulas in the CA1 region of the dorsal hippocampus and basolateral amygdala (BLA), trained in a step-through type passive avoidance task, and tested 24 h after training to measure memory retrieval. Post-training intra-CA1 microinjection of the nonselective CB1/CB2 receptor agonist WIN55,212-2 (WIN) (0.1-0.5 μg/rat) dose-dependently induced amnesia. ⋯ Furthermore, the inhibitory effect of 0.5 μg/rat of intra-CA1 microinjection of WIN on memory formation was significantly decreased by pre-treatment with intra-BLA microinjection of the NMDA receptor antagonist d-2-amino-5-phosphonopentanoic acid (d-AP5; 0.1 and 0.5 μg/rat, intra-BLA). Intra-BLA microinjection of the same doses of NMDA or d-AP5 by itself did not induce any response on memory retrieval. Taken together, these findings support the existence of a functional interaction between dorsal hippocampal and basolateral amygdaloid neural circuits during processing cannabinoid-induced amnesia.
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While the basic pathways mediating vestibulo-ocular, -spinal, and -collic reflexes have been described in detail, little is known about vestibular projections to central autonomic sites. Previous studies have primarily focused on projections from the caudal vestibular region to solitary, vagal and parabrachial nuclei, but have noted a sparse innervation of the ventrolateral medulla. Since a direct pathway from the vestibular nuclei to the rostral ventrolateral medulla would provide a morphological substrate for rapid modifications in blood pressure, heart rate and respiration with changes in posture and locomotion, the present study examined anatomical evidence for this pathway using anterograde and retrograde tract tracing and immunofluorescence detection in brainstem sections of the rat medulla. ⋯ In the rostral ventrolateral medulla, these processes are highly branched and extremely varicose, primarily directed toward the somata and proximal dendrites of non-catecholaminergic neurons, with minor projections to the distal dendrites of catecholaminergic cells. In the caudal ventrolateral medulla, the axons of vestibular nucleus neurons are more modestly branched with fewer varicosities, and their endings are contiguous with both the perikarya and dendrites of catecholamine-containing neurons. These data suggest that vestibular neurons preferentially target the rostral ventrolateral medulla, and can thereby provide a morphological basis for a short latency vestibulo-sympathetic pathway.
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Compensated respiratory acidosis has been observed in a significant number of patients with active vestibular disease. We therefore hypothesized that the inner ear may play an unrecognized integral role in respiratory control. To test this premise, we investigated whether mice with induced inner ear injury demonstrated any alteration in their respiratory response to inhaled carbon dioxide (CO(2)). ⋯ Inner ear damage significantly reduces the respiratory response to CO(2) inhalation. In addition to the established role of the inner ear organ in hearing and balance, this alludes to an unidentified function of the inner ear and its interconnecting neuronal pathways in respiratory regulation. This finding may offer valuable new clues for disease states with abnormal respiratory control where inner ear dysfunction may be present.
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Chronic stress induces dendritic retraction in the hippocampal CA3 subregion, but the mechanisms responsible for this retraction and its impact on neural circuitry are not well understood. To determine the role of NMDA (N-methyl-d-aspartic acid) receptor (NMDAR)-mediated signaling in this process, we compared the effects of chronic immobilization stress (CIS) on hippocampal dendritic morphology, hypothalamic-pituitary-adrenal (HPA) axis activation, and anxiety-related and hippocampus-dependent behaviors, in transgenic male mice in which the NMDAR had been selectively deleted in CA3 pyramidal cells and in non-mutant littermates. We found that CIS exposure for 10 consecutive days in non-mutant mice effectively induces HPA axis activation and dendritic retraction of CA3 short-shaft pyramidal neurons, but not CA3 long-shaft pyramidal neurons, suggesting a differential cellular stress response in this region. ⋯ Strikingly, chronic stress-induced dendritic retraction was not evident in any of the neurons in either CA3 or CA1 in the mutant mice that had a functional lack of NMDARs restricted to CA3 pyramidal neurons. Interestingly, the prevention of dendritic retraction in the mutant mice had a minimal effect on HPA axis activation and behavioral alterations that were induced by chronic stress. These data support a role for NMDAR-dependent glutamatergic signaling in CA3 in the cell-type specific induction of dendritic retraction in two hippocampal subregions following chronic stress.