Neuroscience
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Modulation of actin and microtubule (MT) dynamics in neurons is implicated in guidance cue-dependent axon outgrowth, branching and pathfinding. Although the role of MTs in axon guidance has been well known, how extracellular guidance signals engage MT behavior in axon branching remains unclear. Previously, we have shown that TUBB3, the most dynamic β-tubulin isoform in neurons, directly binds to deleted in colorectal cancer (DCC) to regulate MT dynamics in Netrin-1-mediated axon guidance. ⋯ Knockdown of DSCAM only, DCC only or both was sufficient to block Netrin-1-induced axon branching of E15 mouse cortical neurons. Knocking down TUBB3 inhibited Netrin-1 induced axon branching as well. These results suggest that DSCAM collaborates with DCC to regulate MT dynamics via direct binding to dynamic TUBB3 in Netrin-1-induced axon branching.
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Motor commands issued by the CNS are based upon memories of past experiences with similar objects, the current state of the hand and arm postures, and sensory input. Thus widespread somatosensory information is available to form precise representations of hand shape on which to base motor commands to match a desired posture or movement. The aim of this study was to examine the extent to which somatosensory information reflecting external influences on independent finger movement is incorporated into the perception of hand shape driving the motor command. ⋯ The hypothesis was that the same synergies (patterns of activation across muscles) would be used to complete the task but would be rescaled with respect to condition. The results demonstrated that rescaling the patterns of multi-muscle activity from the unconstrained condition could not equivalently represent those from the constrained conditions. Thus it appears that external restriction of independent finger movement was signaled by somatosensory feedback and incorporated into the desired state driving the motor command resulting in selective activation of groups of muscles.
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The cholinergic pathways, which originate in the basal forebrain and are responsible for the control of different cognitive processes including learning and memory, are also regulated by some neuropeptides. One of these neuropeptides, galanin (GAL), is involved in both neurotrophic and neuroprotective actions. The present study has evaluated in rats the effects on cognition induced by a subchronic treatment with GAL by analyzing the passive avoidance response, and the modulation of muscarinic cholinergic receptor densities and activities. [(3)H]-N-methyl-scopolamine, [(3)H]-oxotremorine, and [(3)H]-pirenzepine were used to quantify the density of muscarinic receptors (MRs) and the stimulation of the binding of guanosine 5'-(γ-[(35)S]thio)triphosphate by the muscarinic agonist, carbachol, to determine their functionality. ⋯ In addition, the increase of GAL receptor density in the ventral hippocampus and entorhinal cortex in the aCSF group was avoided when GAL was administered. The number of acetylcholinesterase (AChE)-positive neurons was decreased in the nucleus basalis of Meynert of both GAL- and aCSF-treated animals. In summary, GAL improves memory-related abilities probably through the modulation of MR density and/or efficacy in hippocampal areas.
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The brain continues to develop through adolescence when excessive alcohol consumption is prevalent in humans. We hypothesized that binge drinking doses of ethanol during adolescence will cause changes in brain ethanol responses that persist into adulthood. To test this hypothesis Wistar rats were treated with an adolescent intermittent ethanol (AIE; 5 g/kg, i.g. 2 days on-2 days off; P25-P54) model of underage drinking followed by 25 days of abstinence during maturation to young adulthood (P80). ⋯ Binge drinking doses led to the nucleus accumbens (NAc) activation that correlated with the ventral tegmental area (VTA) activation. In contrast to other brain regions, AIE enhanced the adult NAc response to binge drinking doses. These studies suggest that adolescent alcohol exposure causes long-lasting changes in brain responses to alcohol that persist into adulthood.
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Aversive experiences in early life are thought to dispose to psychopathologies such as mood or anxiety disorders. In a two-hit stress model, we assessed the effects of juvenile and/or adult stress on the 5-HT-mediated modulation of synaptic inhibition of ventral dentate gyrus granule cells. Combined but not single stress exposure led to a significant reduction in activity and increased anxiety-like behavior. ⋯ This was also true for the number of granule cells responding with a 5-HT3 receptor-dependent burst of miniature IPSCs. 5-HT3 receptors are expressed on cholecystokinin (CCK)+ basket cells in the hippocampus. In fact, we observed a reduction of steady-state mRNA levels of CCK+ basket cell markers after single juvenile or adult stress and partial recovery after combined stress, thus matching the electrophysiological findings. Adaptive changes in 5-HT-mediated modulation of synaptic inhibition and CCK+ basket cells in the DG may help to maintain normal levels of anxiety after single juvenile or adult stress exposure, as indicated by the increased anxiety that accompanies the loss of this regulation upon combined stress.