Neurobiology of disease
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Neurobiology of disease · Mar 2016
Impaired development of cortico-striatal synaptic connectivity in a cell culture model of Huntington's disease.
Huntington's disease (HD) is a genetically inherited neurodegenerative disease caused by a mutation in the gene encoding the huntingtin protein. This mutation results in progressive cell death that is particularly striking in the striatum. Recent evidence indicates that early HD is initially a disease of the synapse, in which subtle alterations in synaptic neurotransmission, particularly at the cortico-striatal (C-S) synapse, can be detected well in advance of cell death. ⋯ Morphological and electrophysiological data suggest that a combination of pre- and postsynaptic mechanisms contribute to this effect, including a reduction in both the postsynaptic dendritic arborization and the size and replenishment rate of the presynaptic readily releasable pool of excitatory vesicles. Moreover, a chimeric culture strategy confirmed that the most robust impairment in C-S connectivity was only observed when mutant huntingtin was expressed both pre- and postsynaptically. In all, our data demonstrate a progressive HD synaptic phenotype in this co-culture system that may be exploited as a platform for identifying promising therapeutic strategies to prevent early HD-associated synaptopathy.
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Neurobiology of disease · Feb 2016
Electrocorticography reveals beta desynchronization in the basal ganglia-cortical loop during rest tremor in Parkinson's disease.
The pathophysiology of rest tremor in Parkinson's disease (PD) is not well understood, and its severity does not correlate with the severity of other cardinal signs of PD. We hypothesized that tremor-related oscillatory activity in the basal-ganglia-thalamocortical loop might serve as a compensatory mechanism for the excessive beta band synchronization associated with the parkinsonian state. We recorded electrocorticography (ECoG) from the sensorimotor cortex and local field potentials (LFP) from the subthalamic nucleus (STN) in patients undergoing lead implantation for deep brain stimulation (DBS). ⋯ Cortico-cortical coherence and phase-amplitude coupling (PAC) decreased during rest tremor, as did basal ganglia-cortical coherence in the same frequency band. Cortical broadband gamma power was not increased by tremor onset, in contrast to the movement-related gamma increase typically observed at the onset of voluntary movement. These findings suggest that the cortical representation of rest tremor is distinct from that of voluntary movement, and support a model in which tremor acts to decrease beta band synchronization within the basal ganglia-cortical loop.
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Neurobiology of disease · Nov 2015
ReviewBrain-controlled muscle stimulation for the restoration of motor function.
Loss of the ability to move, as a consequence of spinal cord injury or neuromuscular disorder, has devastating consequences for the paralyzed individual, and great economic consequences for society. Functional electrical stimulation (FES) offers one means to restore some mobility to these individuals, improving not only their autonomy, but potentially their general health and well-being as well. FES uses electrical stimulation to cause the paralyzed muscles to contract. ⋯ The rapid development of neural interfacing in the past decade offers the promise of dramatically improved control for these patients, potentially allowing continuous control of FES through signals recorded from motor cortex, as the patient attempts to control the paralyzed body part. While application of these 'brain-machine interfaces' (BMIs) has undergone dramatic development for control of computer cursors and even robotic limbs, their use as an interface for FES has been much more limited. In this review, we consider both FES and BMI technologies and discuss the prospect for combining the two to provide important new options for paralyzed individuals.
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Stroke is among the leading causes of long-term disabilities leaving an increasing number of people with cognitive, affective and motor impairments depending on assistance in their daily life. While function after stroke can significantly improve in the first weeks and months, further recovery is often slow or non-existent in the more severe cases encompassing 30-50% of all stroke victims. The neurobiological mechanisms underlying recovery in those patients are incompletely understood. ⋯ First, BMIs can establish continuous high-dimensional brain-control of robotic devices or functional electric stimulation (FES) to assist in daily life activities (assistive BMI). Second, BMIs could facilitate neuroplasticity, thus enhancing motor learning and motor recovery (rehabilitative BMI). Advances in sensor technology, development of non-invasive and implantable wireless BMI-systems and their combination with brain stimulation, along with evidence for BMI systems' clinical efficacy suggest that BMI-related strategies will play an increasing role in neurorehabilitation of stroke.
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Neurobiology of disease · Oct 2015
GABAA currents are decreased by IL-1β in epileptogenic tissue of patients with temporal lobe epilepsy: implications for ictogenesis.
Temporal lobe epilepsy (TLE) is the most prevalent form of adult focal onset epilepsy often associated with drug-resistant seizures. Numerous studies suggest that neuroinflammatory processes are pathologic hallmarks of both experimental and human epilepsy. In particular, the interleukin (IL)-1β/IL-1 receptor type 1 (R1) axis is activated in epileptogenic tissue, where it contributes significantly to the generation and recurrence of seizures in animal models. ⋯ In TLE specimens from humans, the IL-1β effect was mediated by IL-1R1 and PKC. We also showed that IL-1R1 and IRAK1, the proximal kinase mediating the IL-1R1 signaling, are both up-regulated in the TLE compared with control specimens, thus supporting the idea that the IL-1β/IL-R1 axis is activated in human epilepsy. Our findings suggest a novel mechanism possibly underlying the ictogenic action of IL-1β, thus suggesting that this cytokine contributes to seizure generation in human TLE by reducing GABA-mediated neurotransmission.