Neuron
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Dopaminergic dysregulation can cause motor dysfunction, but the mechanisms underlying dopamine-related motor disorders remain under debate. We used an inducible and reversible pharmacogenetic approach in dopamine transporter knockout mice to investigate the simultaneous activity of neuronal ensembles in the dorsolateral striatum and primary motor cortex during hyperdopaminergia ( approximately 500% of controls) with hyperkinesia, and after rapid and profound dopamine depletion (<0.2%) with akinesia in the same animal. ⋯ During hyperkinesia, corticostriatal activity became largely asynchronous, while during dopamine-depletion the synchronicity increased. Thus, dopamine-related disorders like Parkinson's disease may not stem from changes in the overall levels of cortical activity, but from dysfunctional activity coordination in corticostriatal circuits.
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Review
Neural synchrony in brain disorders: relevance for cognitive dysfunctions and pathophysiology.
Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, novel methods of time series analysis have been developed for the examination of task- and performance-related oscillatory activity and its synchronization. Studies employing these advanced techniques revealed that synchronization of oscillatory responses in the beta- and gamma-band is involved in a variety of cognitive functions, such as perceptual grouping, attention-dependent stimulus selection, routing of signals across distributed cortical networks, sensory-motor integration, working memory, and perceptual awareness. ⋯ The data suggest close correlations between abnormalities in neuronal synchronization and cognitive dysfunctions, emphasizing the importance of temporal coordination. Thus, focused search for abnormalities in temporal patterning may be of considerable clinical relevance.
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Brain-controlled interfaces are devices that capture brain transmissions involved in a subject's intention to act, with the potential to restore communication and movement to those who are immobilized. Current devices record electrical activity from the scalp, on the surface of the brain, and within the cerebral cortex. ⋯ Somatosensory feedback is being added to this control as generated behaviors become more complex. New technology to engineer the tissue-electrode interface, electrode design, and extraction algorithms to transform the recorded signal to movement will help translate exciting laboratory demonstrations to patient practice in the near future.
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Neuropathic pain refers to pain that originates from pathology of the nervous system. Diabetes, infection (herpes zoster), nerve compression, nerve trauma, "channelopathies," and autoimmune disease are examples of diseases that may cause neuropathic pain. The development of both animal models and newer pharmacological strategies has led to an explosion of interest in the underlying mechanisms. ⋯ Abnormal signals arise not only from injured axons but also from the intact nociceptors that share the innervation territory of the injured nerve. This review focuses on how both human studies and animal models are helping to elucidate the mechanisms underlying these surprisingly common disorders. The rapid gain in knowledge about abnormal signaling promises breakthroughs in the treatment of these often debilitating disorders.
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Classic Parkinson's disease (PD) is characterized by fibrillar alpha-synuclein inclusions known as Lewy bodies in the substantia nigra, which are associated with nigrostriatal degeneration. However, alpha-synuclein pathologies accumulate throughout the CNS in areas that also undergo progressive neurodegeneration, leading to dementia and other behavioral impairments in addition to parkinsonism. Although mutations in the alpha-synuclein gene only cause Lewy body PD in rare families, and although there are multiple other, albeit rare, genetic causes of familial parkinsonism, sporadic Lewy body PD is the most common movement disorder, and insights into mechanisms underlying alpha-synuclein-mediated neurodegeneration provide novel targets for the discovery of disease-modifying therapies for PD and related neurodegenerative alpha-synucleinopathies.