Neuroscience
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Comparative Study
Delayed minocycline treatment reduces long-term functional deficits and histological injury in a rodent model of focal ischemia.
The absence of effective treatments for stroke presents a critical need for novel strategies that can reduce ischemic injury. Neuroinflammation following focal ischemia induces secondary injury in the region surrounding the insult, thus anti-inflammatory agents are potential neuroprotectants. Minocycline is one such agent possessing neuroprotective properties, however many studies examining minocycline after ischemia have used minimal delays between ischemia and treatment, short survival periods, and lack measures of functional outcome. ⋯ Subcortical and whole hemisphere infarct volumes were reduced by 41 and 39% respectively in minocycline-treated animals. Further analysis revealed that minocycline attenuated long-term white matter damage adjacent to the striatal injury core, which correlated with sustained functional benefits. This study indicates that delayed minocycline treatment improves long-term functional outcome which is linked to protection of both white and gray matter.
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Comparative Study
Unique presynaptic and postsynaptic roles of Group II metabotropic glutamate receptors in the modulation of thalamic network activity.
The thalamic reticular nucleus (TRN) is a sheet of GABAergic neurons that project to other TRN neurons and to associated thalamocortical relay nuclei. The TRN receives glutamatergic synaptic inputs from cortex as well as reciprocal inputs from the collaterals of thalamocortical neurons. In addition to ionotropic glutamate receptors, metabotropic glutamate receptors (mGluRs) are present in the TRN circuitry. ⋯ Because strong corticothalamic activation is implicated in abnormal thalamic rhythms, we used extracellular recordings in the lateral geniculate nucleus to study the effect of Group II mGluR agonists upon these slow oscillations. We induced approximately 3 Hz spike-and-wave discharge activity through corticothalamic stimulation, and found that such activity was reduced in the presence of the Group II mGluR agonist, (-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268). These data indicate that Group II mGluR reduce the impact of corticothalamic excitation, and that they may be a useful target in the reduction of absence-like rhythms.
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Olvanil ((N-vanillyl)-9-oleamide), a non-pungent transient receptor potential vanilloid type 1 agonist, desensitizes nociceptors and alleviates pain. But its molecular targets and signaling mechanisms are little known. Calcium influx through voltage-activated Ca(2+) channels plays an important role in neurotransmitter release and synaptic transmission. ⋯ In addition, double immunofluorescence labeling revealed that olvanil induced a rapid internalization of Ca(V)2.2 immunoreactivity from the membrane surface of dorsal root ganglion neurons. Collectively, this study suggests that stimulation of non-pungent transient receptor potential vanilloid type 1 inhibits voltage-activated Ca(2+) channels through a biochemical pathway involving intracellular Ca(2+)-calmodulin and calcineurin in nociceptive neurons. This new information is important for our understanding of the signaling mechanisms of desensitization of nociceptors by transient receptor potential vanilloid type 1 analogues and the feedback regulation of intracellular Ca(2+) and voltage-activated Ca(2+) channels in nociceptive sensory neurons.
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Comparative Study
Selective mechanisms for complex visual patterns revealed by adaptation.
A great deal is known about the initial steps of visual processing. We know that humans have neural mechanisms selectively tuned to simple patterns of particular spatial frequencies and orientations. ⋯ Very little is known about intermediate levels of visual processing, where early visual signals are presumably combined to represent increasingly complex visual features. Here we show the existence of visual mechanisms in humans, tuned and selective to particular combinations of simple sinusoidal patterns, using a novel method of compound adaptation.
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Comparative Study
Absence of GABA type A signaling in adult medial habenular neurons.
Neural inhibition in the brain is mainly mediated by ionotropic GABA type A receptors. Apart from the GABA type A receptors, both K(+)-Cl(-) cotransporter isoform 2 and the GABA-synthesizing enzyme, glutamic acid decarboxylase, are essential determinants for GABA type A receptor-mediated inhibition. By using immunofluorescent staining, we observed that K(+)-Cl(-) cotransporter isoform 2, GABA type A receptor beta2/3 subunits and a presynaptically localized glutamic acid decarboxylase isoform, glutamic acid decarboxylase 65, were all absent in adult Sprague-Dawley rat medial habenular nucleus, while immunopositive staining for glutamic acid decarboxylase 67, GABA and GABA type B receptor type 2 subunit were present in the medial habenular nucleus. ⋯ These results support the idea that GABAergic transmission in medial habenular nucleus is probably not mediated by any of the most common GABA type A receptor subtypes. Our data suggest that GABA type B receptor-mediated inhibition may play a role in balancing neuronal excitation in this special region. Further exploration for factors determining medial habenular nucleus neural inhibition will lead to a more complete understanding of control of synaptic balance in the CNS.