Neuroscience
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The article reviews evidence for sensitive periods in the sensory systems and considers their neuronal mechanisms from the viewpoint of the system's neuroscience. It reviews the essential cortical developmental steps and shows its dependence on experience. It differentiates feature representation and object representation and their neuronal mechanisms. ⋯ Additional to developmental molecular effects on synaptic plasticity, a combination of several integrative effects of deprivation on brain functions, including feature representation (affecting the starting point for learning), categorization function, top-down interactions and cross-modal reorganization close the sensitive periods and may contribute to their critical nature. Further, non-auditory effects of auditory deprivation are discussed. To reopen critical periods, removal of molecular breaks in synaptic plasticity and focused training therapy on the integrative effects are required.
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Accumulating evidence indicates that activation of spinal cord astrocytes contributes importantly to nerve injury and inflammation-induced persistent pain and chronic opioid-induced antinociceptive tolerance. Phosphorylation of extracellular signal-regulated kinase (pERK) and induction of interleukin-1 beta (IL-1β) in spinal astrocytes have been implicated in astrocytes-mediated pain. Tissue plasminogen activator (tPA) is a serine protease that has been extensively used to treat stroke. ⋯ Intrathecal injection of tPA results in up-regulation of GFAP and pERK in spinal astrocytes but not up-regulation of ionized calcium binding adapter molecule 1 in spinal microglia. Finally, intrathecal tPA elicits persistent mechanical allodynia, which is inhibited by the astroglial toxin alpha-amino adipate and the MEK (ERK kinase) inhibitor U0126. Collectively, these data suggest an important role of tPA in regulating astrocytic signaling, pain hypersensitivity, and morphine tolerance.
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The endocannabinoid system is implicated in the neurobiology of cocaine addiction. This study evaluated the status of cannabinoid (CB) CB1 and CB2 receptors, the endocytic cycle of CB1 receptors, G protein-coupled receptor regulatory kinases (GRK), and associated signaling (mammalian target of rapamicin (mTOR) and 70kDa ribosomal protein S6 kinase (p70S6K)) in brain cortices of drug abusers and cocaine- and cannabinoid-treated rodents. The main results indicate that in cocaine adddicts, but not in mixed cocaine/opiate or opiate abusers, CB1 receptor protein in the prefrontal cortex (PFC) was reduced (-44%, total homogenate) with a concomitant receptor redistribution and/or internalization (decreases in membranes and increases in cytosol). ⋯ Chronic cocaine in mice was associated with tolerance to the acute activation of mTOR and p70S6K. In long-term cocaine addicts, mTOR and p70S6K activations were not altered when compared with controls, indicating that CB1 receptor signaling was dampened. The dysregulation of CB1 receptor, GRK2/3/5, and mTOR/p70S6K signaling by cocaine may contribute to alterations of neuroplasticity and/or neurotoxicity in brains of cocaine addicts.
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Goal-directed reaching is important for the activities of daily living. Populations of neurons in the primary motor cortex that project to spinal motor circuits are known to represent the kinematics of reaching movements. We investigated whether repetitive practice of goal-directed reaching movements induces use-dependent plasticity of those kinematic characteristics, in a manner similar to finger movements, as had been shown previously. ⋯ Direction and the position of the point of peak velocity of TMS-evoked movements were significantly altered following training and at a 5-min interval following training, while amplitude did not show significant changes. This was accompanied by changes in the motor-evoked potentials (MEPs) of the shoulder and elbow agonist muscles that partly explained the change in direction, mainly by increase in agonist MEP, without significant changes in antagonists. These findings demonstrate that the arm representation accessible by motor cortical stimulation under goes rapid plasticity induced by goal-directed robotic reach training in healthy subjects.
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Over the years it has become crystal clear that a variety of processes encode time-of-day information, ranging from gene expression, protein stability, or subcellular localization of key proteins, to the fine tuning of network properties and modulation of input signals, ultimately ensuring that physiology and behavior are properly synchronized to a changing environment. The purpose of this review is to put forward examples (as opposed to generate a comprehensive revision of all the available literature) in which the circadian system displays a remarkable degree of plasticity, from cell autonomous to circuit-based levels. In the literature, the term circadian plasticity has been used to refer to different concepts. ⋯ The discovery of daily remodeling of neuronal structures will be referred herein as structural circadian plasticity, and represents an additional and novel phenomenon modified daily. Finally, any plasticity that has to do with a circadian parameter would represent a type of circadian plasticity; as an example, adjustments that allow organisms to adapt their daily behavior to the annual changes in photoperiod is a form of circadian plasticity at a higher organizational level, which is an emergent property of the whole circadian system. Throughout this work we will revisit these types of changes by reviewing recent literature delving around circadian control of clock outputs, from the most immediate ones within pacemaker neurons to the circadian modulation of rest-activity cycles.