Neuroscience
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How is motor learning affected by aging? Although several experimental paradigms have been used to address this question, there has been limited focus on the early phase of motor learning, which involves motor exploration and the need to coordinate multiple degrees of freedom in the body. Here, we examined motor learning in a body-machine interface where we measured both age-related differences in task performance as well as the coordination strategies underlying this performance. Participants (N = 65; age range 18-72 years) wore wireless inertial measurement units on the upper body, and learned to control a cursor on a screen, which was controlled by motions of the trunk. ⋯ However, we also found that these changes were associated with limited exploration in older adults. Moreover, when considering data across a majority of the lifespan (including children), longer movement times were associated with greater inefficiency of the coordination pattern, producing more task-irrelevant motion. These results suggest exploration behaviors during motor learning are affected with aging, and highlight the need for different practice strategies with aging.
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Coagulation factor XII (FXII) is synthesized in the liver and secreted into the circulation, where it initiates the contact activation system. Although typically thought to be restricted to the circulation, FXII protein has been found in the brain of Alzheimer's disease (AD) and multiple sclerosis patients. Moreover, activation of the contact system has been detected in the cerebrospinal fluid of these patients as well as in the brain of healthy and AD individuals. ⋯ We show that a recombinant version of this shorter FXII protein is activated by plasma kallikrein, reciprocally activates prekallikrein, and converts pro-hepatocyte growth factor (HGF) to active HGF in vitro. HGF-Met signaling plays a role in neuronal development and survival, and its dysregulation has been implicated in neurodevelopmental disorders and neurodegeneration. Taken together, our results show that a short isoform of FXII mRNA is expressed in the brain and raise the possibility that brain-derived FXII may be involved in HGF-Met signaling in neurons.
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One deficit associated with schizophrenia (SZ) is the reduced ability to distinguish self-caused sensations from those due to external sources. This reduced sense of agency (SoA, subjective awareness of control over one's actions) is hypothesized to result from a diminished utilization of internal monitoring signals of self-movement (i.e., efference copy) which subsequently impairs forming and utilizing sensory prediction errors (differences between the predicted and actual sensory consequences resulting from movement). Another important function of these internal monitoring signals is the facilitation of higher-order mechanisms related to motor learning and control. ⋯ Although adaptation was similar for SZP and controls, the extent of generalization was significantly less for SZP; movement trajectories made by patients to the furthest untrained target (135o) before and after adaptation were largely indistinguishable. Interestingly, deficits in generalization were correlated with positive symptoms of psychosis in SZP (e.g., hallucinations). Generalization was also associated with measures of SoA across both SZP and HC, emphasizing the role action awareness plays in motor behavior, and suggesting that misattributing agency, even in HC, manifests in abnormal motor performance.
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Stroke is a devastating brain disorder. The pathophysiology of stroke is associated with an impaired excitation-inhibition balance in the area that surrounds the infarct core after the insult, the peri-infarct zone. Here we exposed slices from adult mouse prefrontal cortex to oxygen-glucose deprivation and reoxygenation (OGD-RO) to study ischemia-induced changes in the activity of excitatory pyramidal neurons and inhibitory parvalbumin (PV)-positive interneurons. ⋯ Disynaptic inhibitory postsynaptic currents (dIPSCs) in pyramidal neurons produced predominantly by PV-positive interneurons were reduced by OGD-RO. Following OGD-RO, dendrites of PV-positive interneurons exhibited more pathological beading than those of pyramidal neurons. Our data support the hypothesis that the differential vulnerability to ischemia-like conditions of excitatory and inhibitory neurons leads to the altered excitation-inhibition balance associated with stroke pathophysiology.
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White matter lesions due to cerebral hypoperfusion may be an important pathophysiology in vascular dementia and stroke, although the inherent mechanisms remain to be fully elucidated. The present study, using a mouse model of chronic cerebral hypoperfusion, examined the white matter protective effects of levetiracetam, an anticonvulsant, via the signaling cascade from the activation of cAMP-responsive element binding protein (CREB) phosphorylation. Mice underwent bilateral common carotid artery stenosis (BCAS), and were separated into the levetiracetam group (injected once only after BCAS [LEV1] or injected on three consecutive days [LEV3]), the vehicle group, or the anti-epileptic drugs with different action mechanisms phenytoin group (PHT3; injected on three consecutive days with the same condition as in LEV3). ⋯ The activation of microglia and astrocytes was markedly suppressed, although the number of oligodendrocyte precursor cells (OPCs) and GST-pi-positive-oligodendrocytes was markedly higher in the cerebral white matter. Moreover, oxidative stress was significantly reduced. We found that 3-day treatment with levetiracetam maintained SV2A protein expression via interaction with astrocytes, which influenced the OPC lineage through activation of CREB to protect white matter from ischemia.