Neuroscience
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Functional effect of short-term immobilization: kinematic changes and recovery on reaching-to-grasp.
Although previous investigations agree in showing significant cortical modifications related to short-term limb immobilization, little is known about the functional changes induced by non-use. To address this issue, we studied the kinematic effect of 10h of hand immobilization. In order to prevent any movement, right handed healthy participants wore on their dominant hand a soft bandage. ⋯ The present findings show firstly that the transport phase of the reaching-to-grasp task was affected by a temporary reduction of sensory and motor information. Secondly, a trial-by-trial recovery of the immobilization-related changes, likely driven by the sensory inputs and motor outputs associated to the repetition of the movement has been observed. All together these results confirm a fundamental role of a continuous stream of sensorimotor signals in maintaining motor efficiency and in driving recovery process.
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Basal ganglia are a network of interconnected nuclei, involved in motor control, goal-directed behaviors and procedural learning. Basal ganglia process information from the cerebral cortex through three main pathways. The striatum is the input nucleus of the direct (cortico-striato-nigral) and indirect (cortico-striato-pallido-subthalamo-nigral) pathways while the subthalamic nucleus (STN) is the input structure of the hyperdirect (cortico-subthalamo-nigral) pathway. ⋯ STN stimulations evoked monosynaptic glutamatergic events in SNr neurons with a mean latency of 2.5 ms and a mean amplitude of 116 pA. This brain slice also preserved a part of the direct and indirect pathways such as the cortico-striatal connection. This novel slice configuration containing the hyperdirect pathway is a useful tool to better understand the transmission and plasticity in this pathway and hence the physiology and the pathophysiology of basal ganglia.
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The striatum is particularly vulnerable to mitochondrial dysfunction and this problem is linked to pathology created by environmental neurotoxins, stimulants like amphetamine, and metabolic disease and ischemia. We studied the course of recovery following a single systemic injection of the mitochondrial complex II inhibitor 3-nitropropionic acid (3-NP) and found 3-NP caused lasting changes in motor behavior that were associated with altered activity-dependent plasticity at corticostriatal synapses in Fischer 344 rats. The changes in synapse behavior varied with the time after exposure to the 3-NP injection. ⋯ Thereafter, the likelihood and degree of inducing D2 DA receptor dependent long-term depression (LTD) gradually increased, relative to saline controls, peaking at 1 month after the 3-NP exposure. NMDA receptor binding did not change over the same post 3-NP time points. These data indicate even brief exposure to 3-NP can have lasting behavioral effects mediated by changes in the way DA and glutamate synapses interact.
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The cellular prion protein (PrP(C)) is a neuronal-anchored glycoprotein that has been associated with several functions in the CNS such as synaptic plasticity, learning and memory and neuroprotection. There is great interest in understanding the role of PrP(C) in the deleterious effects induced by the central accumulation of amyloid-β (Aβ) peptides, a pathological hallmark of Alzheimer's disease, but the existent results are still controversial. ⋯ The protection against Aβ(1-40)-induced cognitive impairments observed in Tg-20 mice was accompanied by a significant decrease in the hippocampal expression of the activated caspase-3 protein and Bax/Bcl-2 ratio as well as reduced hippocampal cell damage assessed by MTT and propidium iodide incorporation assays. These findings indicate that the overexpression of PrP(C) prevents Aβ(1-40)-induced spatial learning and memory deficits in mice and that this response is mediated, at least in part, by the modulation of programed cell death pathways.
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Psychiatric disorders are fairly common comorbidities of epilepsy in humans. Following pilocarpine-induced status epilepticus (SE), experimental animals not only developed spontaneous recurrent seizures, but also exhibited significantly elevated levels of aggressive behavior. ⋯ Treatment with rapamycin, a potent mTOR (mammalian target of rapamycin pathway)-pathway inhibitor, markedly diminished aggressive behavior. Therefore, the mTOR pathway may have significance in the underlying molecular mechanism leading to aggression associated with epilepsy.