Neuroscience
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Age- and menopause-related deficits in working memory can be partially restored with estradiol replacement in women and female nonhuman primates. Working memory is a cognitive function reliant on persistent firing of dorsolateral prefrontal cortex (dlPFC) neurons that requires the activation of GluN2B-containing glutamate NMDA receptors. We tested the hypothesis that the distribution of phospho-Tyr1472-GluN2B (pGluN2B), a predominant form of GluN2B seen at the synapse, is sensitive to aging or estradiol treatment and coupled to working memory performance. ⋯ On the other hand, the percentage of pGluN2B gold particles in the spine cytoplasm was decreased with E treatment in young, but increased with E in aged monkeys. In aged monkeys, DR average accuracy inversely correlated with the percentage of synaptic pGluN2B, while it positively correlated with the percentage of cytoplasmic pGluN2B. Together, E replacement may promote cognitive health in aged monkeys, in part, by decreasing the relative representation of synaptic pGluN2B and potentially protecting the dlPFC from calcium toxicity.
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The ability to recognize a tool's affordances (how a spoon should be appropriately grasped and used), is vital for daily life. Prior research has identified parietofrontal circuits, including mirror neurons, to be critical in understanding affordances. However, parietofrontal action-encoding regions receive extensive visual input and are adjacent to parietofrontal attention control networks. ⋯ Particularly, only overt gaze toward the hand-tool interaction engaged mirror neurons (frontal N400) when discerning grasps that manipulate but not functionally use a tool - (grasp bowl rather than stem of spoon). Results here detail the first human electrophysiological evidence on how attention selectively modulates multiple parietofrontal grasp-perception circuits, especially the mirror neuron system, while unaffecting parietofrontal encoding of tool-use contexts. These results are pertinent to neurophysiological models of affordances that typically neglect the role of attention in action perception.
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The serotoninergic 5-HT2A receptor is involved in the mechanism of depression and antidepressant drugs action. Earlier we showed that striatal-enriched protein tyrosine phosphatase (STEP) inhibitor - 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153) affects both the brain serotoninergic system and the brain-derived neurotropic factor that are known to be involved in the psychopathology of depression. In the present study we investigated the effects of chronic TC-2153 administration on behavior in the standard battery of tests as well as the effects of acute and chronic TC-2153 treatment on the brain 5-HT2A receptors in mice. ⋯ Moreover, both acute and chronic TC-2153 administration inhibited the functional activity of 5-HT2A receptors estimated by the number of 2,5-dimethoxy-4-iodoamphetamine (DOI, agonist of 5-HT2A receptors)-induced head-twitches. TC-2153 treatment also attenuated the DOI-induced c-fos expression in cortical and hippocampal neurons and reduced the 5-HT2A receptor protein level in the hippocampus and frontal cortex, but not in the striatum. Taken together, our combined data demonstrate that the antidepressant effect of STEP inhibitor TC-2153 could be mediated by its inhibitory properties towards the 5-HT2A receptor-mediated signaling.
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Being able to inhibit an impending movement in response to a contextual change is a distinctive feature of action control. Such inhibitory control relies on a complex cortical-subcortical network, including posterior prefrontal regions such as caudal inferior frontal gyrus and pre-supplementary motor area. According to hierarchical models of action control, both areas represent the intermediate level between prefronto-dependent and motor-related cortices. ⋯ Effective TMS on SMA-proper produced no effect on STOP trials' performance (p = 0.31) nor in the GO trial performance (p = 0.56). Our data show that there is at least a portion of PMCd playing a distinctive role in the control of mouth-related M1 during instructed visuomotor inhibitory behavior. This region could therefore represent a low-level hierarchical node for externally cued action inhibition.
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Previously we described similarities and differences in the organization and molecular composition of an aggrecan based extracellular matrix (ECM) in three precerebellar nuclei, the inferior olive, the prepositus hypoglossi nucleus and the red nucleus of the rat associated with their specific cytoarchitecture, connection and function in the vestibular system. The aim of present study is to map the ECM pattern in a mesencephalic precerebellar nucleus, the pararubral area, which has a unique function among the precerebellar nuclei with its retinal connection and involvement in the circadian rhythm regulation. ⋯ Characteristic perineuronal nets (PNNs) were only recognizable with Wisteria floribunda agglutinin (WFA) and aggrecan staining around some of the medium-sized neurons, whereas the small cells were rarely surrounded by a weakly stained PNNs. The moderate expression of key molecules of PNN, the hyaluronan (HA) and HAPLN1 suggests that the lesser stability of ECM assembly around the pararubral neurons may allow quicker response to the modified neuronal activity and contributes to the high level of plasticity in the vestibular system.