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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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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Deficits in dopaminergic function are thought to underlie attention-deficit/hyperactivity disorder (ADHD). Dopaminergic neurons are the main source of dopamine (DA), a neurotransmitter that acts as a neuromodulator of cognitive function in the prefrontal cortex, including the anterior cingulate cortex (ACC), which receives dopaminergic inputs from the ventral tegmental area. The spontaneously hypertensive rat (SHR) has been widely studied as an animal model of ADHD. ⋯ Furthermore, DA activity enhanced the amplitude of evoked and unitary IPSCs from fast-spiking interneurons; the amplitude was also larger in control WKY than in SHRs. Notably, the amplitude of evoked IPSCs was enhanced by the activation of D1-like receptor-mediated pathways. These results suggest that hypofunction of D1-like receptor-mediated regulation of GABAergic inhibitory synaptic transmission onto layer V pyramidal cells of the ACC may contribute to the pathophysiology of ADHD.
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Mitochondrial Carrier Homolog 2 (MTCH2) acts as a receptor for the BH3 interacting-domain death agonist (BID) in the mitochondrial outer membrane. Loss of MTCH2 affects mitochondria energy metabolism and function. MTCH2 forebrain conditional KO (MTCH2 BKO) display a deficit in hippocampus-dependent cognitive functions. ⋯ MTCH2 BKO exhibit impaired spatial but not motor learning and an impairment in long-term potentiation (LTP) in hippocampal slices. Moreover, MTCH2 BKO express an increase in activated microglia, in addition to a reduction in neuron density in the hippocampus, but do not express amyloid-β plaques or neurofibrillary tangles. These results highlight the role of mitochondria in the normal hippocampus-dependent memory formation.
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Stress during development can shift the typical developmental trajectory. Maternal stress prior to conception has recently been shown to exert similar influences on the offspring. The present study questioned if a consistent maternal stressor prior to conception (elevated platform stress) would impact the pre-weaning development of offspring brain and behavior, and if maternal care was vulnerable to this experience. ⋯ The current study failed to find an effect of maternal preconception stress on early behavioral development. These results suggest that the PFC, and likely behavior dependent on the PFC, is vulnerable to maternal preconception stress and that a strong sex effect is evident. Further studies should examine how such offspring fare using a lifespan model and investigate potential mechanisms responsible for these effects.