The Journal of neuroscience : the official journal of the Society for Neuroscience
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Human C-tactile (CT) afferents respond vigorously to gentle skin stroking and have gained attention for their importance in social touch. Pharmacogenetic activation of the mouse CT equivalent has positively reinforcing, anxiolytic effects, suggesting a role in grooming and affiliative behavior. We recorded from single CT axons in human participants, using the technique of microneurography, and stimulated a unit's receptive field using a novel, computer-controlled moving probe, which stroked the skin of the forearm over five velocities (0.3, 1, 3, 10, and 30 cm s(-1)) at three temperatures (cool, 18 °C; neutral, 32 °C; warm, 42 °C). ⋯ Furthermore, the CT firing frequency correlated with hedonic ratings to the same mechano-thermal stimulus only at the neutral stimulus temperature, where the stimuli were felt as pleasant at higher firing rates. We conclude that CT afferents are tuned to respond to tactile stimuli with the specific characteristics of a gentle caress delivered at typical skin temperature. This provides a peripheral mechanism for signaling pleasant skin-to-skin contact in humans, which promotes interpersonal touch and affiliative behavior.
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3,4-Dihydroxyphenyl-L-alanine (L-DOPA)-induced dyskinesia (LID) is a debilitating side effect of long-term dopamine replacement therapy in Parkinson's Disease. At present, there are few therapeutic options for treatment of LID and mechanisms contributing to the development and maintenance of these drug-induced motor complications are not well understood. We have previously shown that pharmacological reduction of cholinergic tone attenuates the expression of LID in parkinsonian mice with established dyskinesia after chronic L-DOPA treatment. ⋯ We show that Cre recombinase-mediated DT-A ablation selectively eliminated ChIs when injected into striatum. The depletion of ChIs markedly attenuated LID without compromising the therapeutic efficacy of L-DOPA. These results provide evidence that ChIs play a key and selective role in LID and that strategies to reduce striatal cholinergic tone may represent a promising approach to decreasing L-DOPA-induced motor complications in Parkinson's disease.
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The basal forebrain (BF) plays an important role in the control of cortical activation and attention. Understanding the modulation of BF neuronal activity is a prerequisite to treat disorders of cortical activation involving BF dysfunction, such as Alzheimer's disease. Here we reveal the interaction between cholinergic neurons and cortically projecting BF GABAergic neurons using immunohistochemistry and whole-cell recordings in vitro. ⋯ Furthermore, optogenetic stimulation of cholinergic neurons/fibers caused a mecamylamine- and atropine-sensitive inward current in putative GABAergic neurons. Thus, cortically projecting, BF GABAergic/PV neurons are excited by neighboring BF and/or brainstem cholinergic neurons. Loss of cholinergic neurons in Alzheimer's disease may impair cortical activation, in part, through disfacilitation of BF cortically projecting GABAergic/PV neurons.
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As we begin to acquire a new motor skill, we face the dual challenge of determining and refining the somatosensory goals of our movements and establishing the best motor commands to achieve our ends. The two typically proceed in parallel, and accordingly it is unclear how much of skill acquisition is a reflection of changes in sensory systems and how much reflects changes in the brain's motor areas. Here we have intentionally separated perceptual and motor learning in time so that we can assess functional changes to human sensory and motor networks as a result of perceptual learning. ⋯ We used this model in combination with a partial correlation technique to parcel out those changes in connectivity observed in motor systems that could be attributed to activity in sensory brain regions. We found that, after removing effects that are linearly correlated with somatosensory activity, perceptual learning results in changes to frontal motor areas that are related to the effects of this training on motor behavior and learning. This suggests that perceptual learning produces changes to frontal motor areas of the brain and may thus contribute directly to motor learning.
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Adipose tissue is a known source of proinflammatory cytokines in obese humans and animal models, including the db/db mouse, in which obesity arises as a result of leptin receptor insensitivity. Inflammatory cytokines induce cognitive deficits across numerous conditions, but no studies have determined whether obesity-induced inflammation mediates synaptic dysfunction. To address this question, we used a treadmill training paradigm in which mice were exposed to daily training sessions or an immobile belt, with motivation achieved by delivery of compressed air on noncompliance. ⋯ Levels of interleukin 1β (IL1β) emerged as a correlate of adiposity and cognitive impairment across both the treadmill and lipectomy studies, so we manipulated hippocampal IL1 signaling using intrahippocampal delivery of IL1 receptor antagonist (IL1ra). Intrahippocampal IL1ra prevented synaptic dysfunction, proinflammatory priming, and cognitive impairment. This pattern supports a central role for IL1-mediated neuroinflammation as a mechanism for cognitive deficits in obesity and diabetes.