Neuroscience
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Parkinson's Disease (PD) is a multi-system neurodegenerative disease where approximately 90% of cases are idiopathic. The remaining 10% of the cases can be traced to a genetic origin and research has largely focused on these associated genes to gain a better understanding of the molecular and cellular pathogenesis for PD. The gene encoding vacuolar protein sorting protein 35 (VPS35) has been definitively linked to late onset familial PD following the identification of a point mutation (D620N) as the causal agent in a Swiss family. ⋯ In this review, we examine what is currently known about VPS35, which has pleiotropic effects, as well as proposed mechanisms of pathogenesis by the D620N mutation. A brief survey of other VPS35 polymorphisms is also provided. Lastly, model systems that are being utilized for these investigations and possible directions for future research are discussed.
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We used force-matching tasks between the two hands to test predictions of the recently introduced scheme of perception based on the concept of iso-perceptual manifold (IPM) in the combined afferent-efferent space of neural signals. The main hypothesis was that accuracy and variability of individual finger force matching would be worse in a four-finger task compared to one-finger tasks. The subjects produced accurate force levels under visual feedback by pressing with either all four fingers or by one of the fingers of a hand (task-hand). ⋯ Matching hypothetical commands to fingers, rather than finger forces, could be responsible for the consistent force overshoots. Indices of inter-trial variance affecting and unaffecting total force showed strong stabilization of total force in the task-hand but not in the match-hand in support of an earlier hypothesis on the importance of visual feedback for force stabilization. No differences were seen between the right and left hands suggesting that the dynamic dominance hypothesis may not be generalizable to perceptual phenomena.
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Human bipedal balance control is proposed to be the integrated activity of distributed neural areas. There is growing understanding about the cortical involvement in this highly automated behavior. While evidence exists for cortical activity temporally linked to reactive balance control, little is known about the functional interaction of potential cortical regions. ⋯ The results suggest that there might exist a balance control cortical network while standing and rapid, transient, and frequency-specific reorganization occurs in this network during reactive balance control events. This reorganization was characterized by an increased number of short-range connections between neighboring areas and increased strength between connections in delta, theta, alpha, and beta frequency bands during PEP N1 compared to baseline. To our knowledge, this is the first study to report the existence of functional cortical networks during reactive balance control with potential implications on assessing impaired balance associated with various neural diseases.
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The striatum of the basal ganglia is pivotal for voluntary movements and is implicated in debilitating movement disorders such as Parkinsonism and dystonia. Striatum projects to downstream nuclei through direct (dSPN) and indirect (iSPN) pathway projection neurons thought to exert opposite effects on movement. In rodent models of striatal function, unilateral dopamine deprivation induces ipsiversive rotational behavior. ⋯ Bursts of ipsiversive rotations were interspersed with normal ambulation. However, partial unilateral inhibition of ∼20% of dorsostriatal dSPNs did not affect horizontal and vertical locomotion or forelimb use preference. Overall, our results substantiate a unique role of dSPNs in promoting response bias in rotational behavior and show this to be a highly sensitive measure of dSPN performance.
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The endocannabinoid system (ECS) regulates several physiological processes in the Central Nervous System, including the modulation of neuronal excitability via activation of cannabinoid receptors (CBr). Both glutaric acid (GA) and quinolinic acid (QUIN) are endogenous metabolites that, under pathological conditions, recruit common toxic mechanisms. A synergistic effect between them has already been demonstrated, supporting potential implications for glutaric acidemia type I (GA I). ⋯ The use of the CB1 receptor reverse agonist AM251 in both biological preparations prevented partially the protective effects exerted by AEA, thus suggesting a partial role of CB1 receptors in this toxic model. AEA also prevented the cell damage and apoptotic death induced by the synergic model in cell cultures. Altogether, these findings demonstrate a modulatory role of the ECS on the synergic toxic actions exerted by QUIN + GA, thus providing key information for the understanding of the pathophysiological events occurring in GA I.