Neuroscience
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Levodopa-induced dyskinesias are abnormal involuntary movements that limit the effectiveness of treatments for Parkinson's disease. Although dyskinesias involve the striatum, it is unclear how striatal neurons are involved in dyskinetic movements. Here we record from striatal neurons in mice during levodopa-induced axial dyskinesias. ⋯ We also found that delta field potential power increased in the striatum with dyskinesia, and that this increased delta power coupled with striatal neurons. Our findings provide insight into how striatal networks change as levodopa-induced dyskinesias develop, and suggest that increased medium spiny neuron firing, increased delta field potential power, and abnormal delta-coupling may be neurophysiological signatures of dyskinesias. These data could be helpful in understanding the role of the striatum in the pathogenesis of dyskinesias in Parkinson's disease.
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Freezing of gait (FoG) in people with Parkinson's disease (PD) is an environmentally sensitive, intermittent problem that occurs most often during turning. FoG is difficult for clinicians to evaluate and treat because it can be difficult to elicit during a clinical visit. Here, we aimed to develop a clinically valid objective measure of freezing severity during a 2-min 360-degree turning-in-place. ⋯ The Freezing Ratio during the turning test was significantly correlated with the clinical ratings (ρ=0.7, p=0.003) and with score on the new FoG questionnaire (ρ=0.5, p=0.03). After correcting for symptom severity (UPDRS-III), out of the four objective measures of the turning test (total number of turns, average turn peak speed and average turn smoothness), only the Freezing Ratio was significantly different across groups (p=0.04). Freezing can be well quantified with body-worn inertial sensors during a 2-min turning-in-place protocol.
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The central canal along the spinal cord (SC.) and medulla is characterized by the presence of a specific population of neurons that contacts the cerebrospinal fluid (CSF). These medullo-spinal CSF-contacting neurons (CSF-cNs) are identified by the selective expression of the polycystin kidney disease 2-like 1 ionic channel (PKD2L1 or polycystin-L). In adult, they have been shown to express doublecortin (DCX) and Nkx6.1, two markers of juvenile neurons along with the neuron-specific nuclear protein (NeuN) typically expressed in mature neurons. ⋯ Nevertheless, CSF-cNs still share in adult characteristics of juvenile neurons such as the presence of phospho-CREB and DCX while NeuN expression remained low. This phenotype persists in 12-month-old animals. Thus, despite a pursuit of neuronal maturation during the postnatal period, CSF-cNs retain a durable low differentiated state.
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The subiculum is a pivotal structure located in the hippocampal formation that receives inputs from grid and place cells and that mediates the output from the hippocampus to cortical and sub-cortical areas. Previous studies have demonstrated the existence of boundary vector cells (BVC) in the subiculum, as well as exceptional stability during recordings conducted in the dark, suggesting that the subiculum is involved in the coding of allocentric cues and also in path integration. In order to better understand the role of the subiculum in spatial processing and the coding of external cues, we recorded subicular units in freely moving rats while performing two experiments: the "size experiment" in which we modified the arena size, and the "barrier experiment" in which we inserted new barriers in a familiar open field thus dividing the enclosure into four comparable sub-chambers. ⋯ In contrast, our results demonstrate heterogeneous space coding by different cell types: place cells, barrier-related units and BVC. We also found units characterized by narrow spike waveforms, most likely belonging to axonal recordings, that showed grid-like patterns. Our data indicate that the subiculum codes space in a flexible manner, and that it is involved in the processing of allocentric information, external cues and path integration, thus broadly supporting spatial navigation.
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Perceiving and reproducing direction of visual stimuli in 2-D space produces the visual oblique effect, which manifests as increased precision in the reproduction of cardinal compared to oblique directions. A second cognitive oblique effect emerges when stimulus information is degraded (such as when reproducing stimuli from memory) and manifests as a systematic distortion where reproduced directions close to the cardinal axes deviate toward the oblique, leading to space expansion at cardinal and contraction at oblique axes. We studied the oblique effect in 3-D using a virtual reality system to present a large number of stimuli, covering the surface of an imaginary half sphere, to which subjects had to reach. ⋯ A visual oblique effect was observed for the reproduction of cardinal directions compared to oblique, which did not differ with memory condition. A cognitive oblique effect also emerged, which was significantly larger in the memory compared to the no-memory condition, leading to distortion of directional space with expansion near the cardinal axes and compression near the oblique axes on the hemispherical surface. This effect provides evidence that existing models of 2-D directional space categorization could be extended in the natural 3-D space.