Neuroscience
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The functional organization of the hippocampus along its longitudinal (septotemporal or dorsoventral) axis is conspicuously heterogeneous. This functional diversification includes the activity of sharp wave and ripples (SPW-Rs), a complex intrinsic network pattern involved in memory consolidation. In this study, using transverse slices from the ventral and the dorsal rat hippocampus and recordings of CA1 field potentials we studied the development of SPW-Rs and possible changes in local network excitability and inhibition, during in vitro maintenance of the hippocampal tissue. ⋯ Furthermore, the amplitude of SPWs positively correlated with the level of maximum excitation of the local neuronal network in both segments of the hippocampus, and the local network excitability and inhibition in the ventral but not the dorsal hippocampus. Blockade of α5 subunit-containing GABAA receptor by L-655,708 significantly reduced the rate of occurrence of SPWs and enhanced the probability of their generation in the form of clusters in the ventral hippocampus without affecting activity in the dorsal hippocampus. The present evidence suggests that a dynamic upregulation of excitation and inhibition in the local neuronal network may significantly contribute to the generation of SPW-Rs, particularly in the ventral hippocampus.
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Neurophysiological and neuroimaging evidence suggests a significant contribution of several brain areas, including subdivisions of the parietal and the premotor cortex, during the processing of different components of hand and arm movements. Many investigations improved our knowledge about the neural processes underlying the execution of reaching and grasping actions, while few studies have directly investigated object manipulation. Most studies on the latter topic concern the use of tools to achieve specific goals. ⋯ Then, we have described the main structures recruited during object manipulation. We have also reported the contribution of recent structural connectivity techniques whereby the cortico-cortical and cortico-subcortical connections of grasping-related and manipulation-related areas in the human brain can be determined. Based on our review, we have concluded that studies on cortical and subcortical circuits involved in grasping and manipulation might be promising to provide new insights about motor learning and brain plasticity in patients with motor disorders.
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Nociception is the neuronal process of encoding noxious stimuli and could be modulated at peripheral, spinal, brainstem, and cortical levels. At cortical levels, several areas including the anterior cingulate cortex (ACC), prefrontal cortex (PFC), ventrolateral orbital cortex (VLO), insular cortex (IC), motor cortex (MC), and somatosensory cortices are involved in nociception modulation through two main mechanisms: (i) a descending modulatory effect at spinal level by direct corticospinal projections or mostly by activation of brainstem structures (i.e. periaqueductal grey matter (PAG), locus coeruleus (LC), the nucleus of raphe (RM) and rostroventral medulla (RVM)); and by (ii) cortico-cortical or cortico-subcortical interactions. ⋯ Besides, we point out the importance of considering intracortical neuronal populations and receptors expression, as well as, nociception-induced cortical changes, both functional and connectional, to better understand this modulatory effect. Finally, we discuss the possible mechanisms that could potentiate the use of cortical stimulation as a promising procedure in pain alleviation.
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Cerebellar Purkinje cells develop the most elaborate dendritic trees among neurons in the brain. To examine the role of Ca2+/calmodulin-dependent protein kinase (CaMK) IIα, IIβ and IV in the dendritic differentiation of Purkinje cells, we introduced siRNA against these CaMKs into Purkinje cells in cerebellar cell cultures using a single-cell electroporation technique. Single-cell electroporation enables us to transfer siRNA into specific cells within a heterogeneous cell population. ⋯ However, the combination of all three siRNA against these CaMKs (triple knockdown) inhibited the branching of Purkinje cell dendrites. Furthermore, the triple knockdown reduced the phosphorylation of CREB in Purkinje cells. These findings suggest the promotion of dendritic differentiation of Purkinje cells by CaMKIIα, IIβ and IV and the possible involvement of phosphorylation of CREB as a common substrate of these CaMKs.
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In everyday life, risky decision-making relies on multiple cognitive processes including sensitivity to reinforcers, exploration, learning, and forgetting. Neuroimaging evidence suggests that the dorsolateral prefrontal cortex (DLPFC) is involved in exploration and risky decision-making, but the nature of its computations and its causal role remain uncertain. We provide evidence for the role of the DLPFC in value-independent, directed exploration on the Iowa Gambling Task (IGT) and we describe a new computational model to account for the competition of directed exploration and exploitation in guiding decisions. ⋯ Applying cTBS to the left and right DLPFC selectively decreased directed exploration on the IGT compared to sham stimulation. Model-based analyses further indicated that the right (but not the left) DLPFC stimulation increased sensitivity to reinforcers, leading to avoidance of risky choices and promoting advantageous choices during the task. Although these findings are based on small sample sizes per group, they nevertheless elucidate the causal role of the right DLPFC in governing the exploration-exploitation tradeoff during decision-making in uncertain and ambiguous contexts.