The Journal of neuroscience : the official journal of the Society for Neuroscience
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Spontaneous activity in the developing brain contributes to its maturation, but how this activity is coordinated between distinct cortical regions and whether it might reflect developing sensory circuits is not well understood. Here, we address this question by imaging the spread and synchronization of cortical activity using voltage-sensitive dyes (VSDs) in the developing rat in vivo. In postnatal day 4-6 rats (n = 10), we collected spontaneous changes in VSD signal that reflect underlying membrane potential changes over a large craniotomy (50 mm2) that encompassed both the sensory and motor cortices of both hemispheres. ⋯ This activity also spread asymmetrically, toward the midline of the brain. We found that the spatial and temporal structure of such spontaneous cortical bursts closely matched that of sensory-evoked activity elicited via direct stimulation of the periphery. These data suggest that spontaneous cortical activity provides a recurring template of functional cortical circuits within the developing cortex and could contribute to the maturation of integrative connections between sensory and motor cortices.
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The cognitive and neuronal mechanisms of perceptual decision making have been successfully linked to sequential sampling models. These models describe the decision process as a gradual accumulation of sensory evidence over time. The temporal evolution of economic choices, however, remains largely unexplored. ⋯ Furthermore, at the beginning of the decision process the fMRI signal in these regions accounted for trial-by-trial deviations from behavioral model predictions: relatively high activation preceded relatively early responses. The updating of value information was correlated with signals in the ventromedial prefrontal cortex, left and right orbitofrontal cortex, and ventral striatum but also in the primary motor cortex well before the response itself. Our results support a view of value-based decisions as emerging from sequential sampling of evidence and suggest a close link between the accumulation process and activity in the motor system when people are free to respond at any time.
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The accumulation of the β-amyloid peptide (Aβ) in Alzheimer's disease (AD) is thought to play a causative role in triggering synaptic dysfunction in neurons, leading to their eventual demise through apoptosis. Aβ is produced and secreted upon sequential cleavage of the amyloid precursor protein (APP) by β-secretases and γ-secretases. However, while Aβ levels have been shown to be increased in the brains of AD patients, little is known about how the cleavage of APP and the subsequent generation of Aβ is influenced, or whether the cleavage process changes over time. ⋯ Here we show that cross-linking of APP is sufficient to raise the levels of Aβ in viable neurons with a concomitant increase in the levels of the β-secretase BACE1. This appears to occur as a result of a sorting defect that stems from the caspase-3-mediated inactivation of a key sorting adaptor protein, namely GGA3, which prevents the lysosomal degradation of BACE1. Together, our data suggest the occurrence of a positive pathogenic feedback loop involving Aβ and APP in affected neurons possibly allowing Aβ to spread to nearby healthy neurons.
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Adolescence is a critical period of brain development during which maturation of areas involved in cognitive functioning, such as the medial prefrontal cortex (mPFC), is still ongoing. Tobacco smoking during this age can compromise the normal course of prefrontal development and lead to cognitive impairments in later life. Recently, we reported that nicotine exposure during adolescence results in a short-term increase and lasting reduction in synaptic mGluR2 levels in the rat mPFC, causing attention deficits during adulthood. ⋯ Short- and long-term adaptation of mPFC synaptic plasticity after adolescent nicotine exposure could be explained by changed mGluR2 signaling. Blocking mGluR2s augmented tLTP, whereas activating mGluR2s reduced tLTP. Our findings suggest neuronal mechanisms by which exposure to nicotine during adolescence alters the rules for spike timing-dependent plasticity in prefrontal networks that may explain the observed deficits in cognitive performance in later life.