The Journal of neuroscience : the official journal of the Society for Neuroscience
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The abuse of synthetic psychoactive substances known as "designer drugs," or "new psychoactive substances" (NPS), is increasing at an alarming rate. NPS are purchased as alternatives to traditional illicit drugs of abuse and are manufactured to circumvent laws regulating the sale and use of controlled substances. ⋯ Despite the popularity of NPS, there is a paucity of scientific data about these drugs. Here we provide a brief up-to-date review describing the mechanisms of action and neurobiological effects of synthetic cathinones and cannabinoids.
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A fundamental capacity of social animals consists in the predictive representation of upcoming events in the outside world, such as the actions of others. Here, we tested the activity of ventral premotor area F5 mirror neurons (MNs) while monkeys observed an experimenter performing (Action condition) or withholding (Inaction condition) a grasping action, which could be predicted on the basis of previously presented auditory instructions. ⋯ MN population activity as a whole displayed an overall predictive activation pattern, becoming active, on average, 340 ms before the go signal. Furthermore, MNs became active earlier when the observed action was performed in the monkeys' extrapersonal rather than peripersonal space, suggesting that context-based neural prediction of others' actions plays different roles depending on the monkeys' ability to interact with the observed agent.
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Synaptic plasticity in hippocampal neurons has been thought to represent a variety of memories. Although accumulating evidence indicates a crucial role of BDNF/TrkB/Akt signaling in the synaptic plasticity of the hippocampus, the mechanism by which Akt, a serine/threonine kinase, controls activity-dependent neuronal plasticity remains unclear. Girdin (also known as APE, GIV, and HkRP1), an actin-binding protein involved both in the remodeling of the actin cytoskeleton and in cell migration, has been identified as a substrate of Akt. ⋯ These phenotypes of Girdin(SA/SA) mice resembled those of Girdin(+/-) mice, which have 50% loss of Girdin expression. Furthermore, Girdin interacted with Src kinase and NR2B subunit of NMDA receptor, leading to phosphorylation of the NR2B subunit and NMDA receptor activation. Our findings suggest that Girdin has two different functions in the hippocampus: Akt-independent neuronal migration and Akt-dependent NR2B phosphorylation through the interaction with Src, which is associated with synaptic plasticity in the hippocampus underlying memory formation.
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Visual working memory (VWM) plays an essential role in many perceptual and higher-order cognitive processes. Despite its reliance on a broad network of brain regions, VWM has a capacity limited to a few objects. This capacity varies substantially across individuals and relates closely to measures of overall cognitive function (Luck and Vogel, 2013). ⋯ Increased f(axon) associates with increased VWM capacity. An additional 12% in VWM capacity variance may be explained by diffusion properties of the extra-axonal space. These data demonstrate, for the first time, the key role of white matter in limiting VWM capacity in the healthy adult brain and suggest that white matter may represent an important therapeutic target in disorders of impaired VWM and cognition.
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Activation of the stress response in the presence of diverse challenges requires numerous adaptive molecular and cellular changes. To identify specific microRNA molecules that are altered following chronic stress, mice were subjected to the chronic social defeat procedure. The amygdala from these mice was collected and a screen for microRNAs that were recruited to the RNA-induced silencing complex and differentially expressed between the stressed and unstressed mice was conducted. ⋯ Interestingly, adult mice injected bilaterally with miR-19b into the BLA showed lower freezing time relative to control in the cue fear conditioning test, and deregulation of noradrenergic circuits, consistent with downregulation of Adrb1 levels. Knockdown of endogenous BLA-miR-19b levels resulted in opposite behavioral and noradrenergic profile with higher freezing time and increase 3-methoxy-4-hydroxyphenylglycol/noradrenaline ratio. These findings suggest a key role for miR-19b in modulating behavioral responses to chronic stress and Adrb1 as an important target of miR-19b in stress-linked brain regions.