Neuroscience
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We examined how motor responses to a stimulus evolve as individuals learn to predict when a stimulus will appear, by comparing responses to a regular versus irregular stimulus train. The study was conducted with two groups of adults - one responded to the regular appearance of a visual stimulus every 3 s (R group) and the second responded to the irregular presentation of the same stimulus (IR group) at intervals varying between 2 and 4 s. Participants responded to the appearance of the stimulus by bending over to press a button that was slightly out of reach. ⋯ Soleus muscle deactivation is an indicator of movement preparation. EMG integrals for this muscle a little before stimulus onset showed a trend for greater decrease in the R group. In summary, our study shows that temporal expectations over repeated stimulus presentation permit the dynamic optimization of motor activity with progressively faster response times, muscle activation onset times and lower muscle activation amplitudes.
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Response inhibition is a central aspect of cognitive control. Usually, response inhibition is examined using information from a single sensory modality. Yet, evidence suggests that conflicts between information from different modalities affect response inhibition. ⋯ This also explains why less intense braking processes (reflected by IFG activity) are still able to maintain a reasonable response inhibition performance level. It can be concluded that the tactile and visual domains do not only differ in regard to their efficiency to trigger response inhibition processes but also in their susceptibility to interference while informing inhibitory control. Clinical implications are discussed.
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The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype of ionotropic glutamate receptors mediates most fast excitatory transmission. Glutamate binding to AMPA receptors (AMPARs) causes most AMPARs to rapidly and completely desensitize, and their desensitization kinetics influence synaptic timing. Thus, factors that alter AMPAR desensitization influence synaptic transmission. ⋯ CTZ completely blocked potentiation by zinc but had no significant effect on inhibition. There was a significant negative correlation between the degree of potentiation of AMPAR-mediated currents by 100 μM zinc and a quantitative measure of the degree of AMPAR desensitization (the steady-state to peak [S:P] ratio of AMPA-evoked currents), but no correlation between the degree of current inhibition by 1 mM zinc and the S:P ratio. Together, these findings suggest that low zinc concentrations potentiate rat OB AMPARs by decreasing receptor desensitization, but that the inhibitory effects of higher zinc concentrations are mediated by a separate mechanism.
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Alzheimer's disease (AD) is the neurodegenerative disorder with no cure. Recent studies suggest that dysregulated postsynaptic store-operated calcium entry (nSOCE) may underlie mushroom spine loss that is related to AD pathology. ⋯ We further established that nSOCE antagonist EVP4593 decreases PSEN1ΔE9-mediated nSOCE upregulation and rescues mushroom spines in PSEN1ΔE9-expressing neurons. Obtained results further highlight the connection between dysregulation of endoplasmic reticulum calcium signaling and synaptic loss in AD and suggest that calcium signaling modulators may have a therapeutic value for treatment of memory loss in AD.
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Neuropeptide Y is a peptide neuromodulator with protective roles including anxiolytic and antidepressant-like effects in animal models of depression and post-traumatic stress disorder. The lateral habenula (LHb) is a brain region that encodes aversive information and is closely related with mood disorders. Although LHb neurons express NPY receptors, the physiological roles of NPY in this region remain uninvestigated. ⋯ Inhibitory transmission remained unchanged by NPY application in a subset of neurons but was reduced in the majority of LHb neurons recorded. The overall outcome of NPY application was a decrease in the spontaneous firing rate of the LHb, leading to hypoactivation of the LHb. Our observations indicate that although NPY has divergent effects on excitatory and inhibitory transmission, NPY receptor activation decreases LHb activity, suggesting that the LHb may partly mediate the protective roles of NPY in the central nervous system.