Neuroscience
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Enteric viscerofugal neurons are interneurons with cell bodies in the gut wall; they project to prevertebral ganglia where they provide excitatory synaptic drive to sympathetic neurons which control intestinal motility and secretion. Here, we studied the mechanosensitivity and firing of single, identified viscerofugal neurons in guinea-pig distal colon. Flat sheet preparations of gut were set up in vitro and conventional extracellular recordings made from colonic nerve trunks. ⋯ They provide a significant primary afferent output from the colon, encoding circumferential length, largely independent of muscle tension. All viscerofugal neurons are directly mechanosensitive, although they have been reported to receive synaptic inputs. In short, viscerofugal neurons combine interneuronal function with length-sensitive mechanosensitivity.
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Recently it has become apparent that microglia play a role not only in responding to insults within the central nervous system but also in responding to changes in synaptic activity and potentially modulating synaptic function. This has led to an enormous expansion of interest in how microglia respond to both pathological and nonpathological challenges, with activities that are associated with unique morphological transformations. Examining changes in microglial morphology can provide direct insight into the cells' functional activities, as morphological status is recognized to be tightly coupled with function. ⋯ This review critically examines the strengths and weaknesses of existing morphometric analysis procedures. This review further examines efforts to improve the utility of existing approaches and discusses new developments, such as digital reconstruction, that yield more accurate and specific information on how microglia remodel themselves. Ultimately, an improved understanding of the strengths and limitations of existing, and emerging, morphometric approaches will greatly facilitate efforts to understand how microglia remodel themselves in response to the full spectrum of challenges that they are known to encounter.
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Traumatic brain injury (TBI) survivors experience long-term post-traumatic morbidities. In diffuse brain-injured rats, a chronic sensory sensitivity to whisker stimulation models the agitation of TBI survivors and provides anatomical landmarks across the whisker-barrel circuit to evaluate post-traumatic neuropathology. As a consequence of TBI, acute and chronic microglial activation can contribute to degenerative and reparative events underlying post-traumatic morbidity. ⋯ Evidence for alternative activation (arginase 1) was not observed. Thus, these data demonstrate concomitant classical activation and acquired deactivation phenotypes of microglia in diffuse TBI in the absence of overt contusion or cavitation. Anti-inflammatory treatment may further alleviate the neuropathological burden of post-traumatic inflammation.
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Alzheimer's disease (AD) is a neurodegenerative aging disorder characterized by extracellular Aβ plaques and intraneuronal neurofibrillary tangles. We conducted longitudinal studies to examine the effects of Aβ on brain amino acid metabolism in lentiviral Aβ(1-42) gene transfer animals and transgenic AD mice. We also performed lentiviral parkin gene delivery to determine the effects of Aβ clearance in AD models. ⋯ Cortical atrophy was observed in aged 3xTg-AD mice, while parkin expression was associated with reduced atrophy. Similarly, Aβ(1-42) resulted in significant cell loss, pronounced astrogliosis and cortical atrophy and parkin reduced astrogliosis and reversed Aβ(1-42) effects on cell loss and cortical atrophy. Taken together these data suggest that parkin prevents amyloid-induced alteration of brain metabolism and may be used as a therapeutic target to limit neuronal loss in AD.
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In adult rat striatum the dopamine D1-D2 receptor heteromer is expressed selectively in a subset of medium spiny neurons (MSNs) that coexpress the dopamine D1 and D2 receptors (D1R and D2R) as well as dynorphin (DYN) and enkephalin (ENK), with higher coexpression in nucleus accumbens (NAc) and much lower in the caudate putamen (CP). In the present study we showed that in neonatal striatal cultured neurons >90% exhibited the D1R/D2R-DYN/ENK phenotype. Similarly, in the striatum of juvenile rats (age 26-28 days) coexpression of D1R and D2R was also coincident with the expression of both DYN and ENK. ⋯ However, within MSNs that coexpressed D1R and D2R, the propensity to form the D1-D2 receptor heteromer did not differ between age groups. Consistent with reduced coexpression of the D1R and D2R, juvenile rats exhibited subsensitivity to D1-D2 receptor heteromer-induced grooming following activation by SKF 83959. Given the proposed role of D1R/D2R-coexpressing MSNs in the regulation of thalamic output, and the recent discovery that these MSNs exhibit both inhibitory and excitatory capabilities, these findings suggest that the functional regulation of neurotransmission by the dopamine D1-D2 receptor heteromer within the juvenile striatum may be significantly different than in the adult.