Neuroscience
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We investigated hemispheric asymmetries in categorization of face gender by means of a divided visual field paradigm, in which female and male faces were presented unilaterally for 150ms each. A group of 60 healthy participants (30 males) and a male split-brain patient (D. D. ⋯ His performance was higher than expected by chance - and did not differ from controls - only for male faces presented in the LVF. The residual right-hemispheric ability of the split-brain patient in categorizing male faces reveals an own-gender bias lateralized in the right hemisphere, in line with the rightward own-identity and own-age bias previously shown in split-brain patients. The gender-contingent hemispheric dominance found in healthy participants confirms the previously shown right-hemispheric superiority in recognizing female faces, and also reveals a left-hemispheric superiority in recognizing male faces, adding an important evidence of hemispheric imbalance in the field of face and gender perception.
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TAK-063 is a selective phosphodiesterase 10A (PDE10A) inhibitor that produces potent antipsychotic-like and pro-cognitive effects at 0.3mg/kg (26% PDE10A occupancy in rats) or higher in rodents through the balanced activation of the direct and indirect pathways of striatal medium spiny neurons (MSNs). In this study, we evaluated the specific binding of TAK-063 using in vitro autoradiography (ARG) and the modulation of brain activity using pharmacological magnetic resonance imaging (phMRI) and electroencephalography (EEG). [3H]TAK-063 significantly accumulated in the caudate-putamen (CPu), ventral pallidum (VP), substantia nigra (SN), hippocampus (Hipp), and amygdala (Amy), but not in the frontal cortex (Fcx), brainstem (Bs), or cerebellum (Cb) in an ARG study using rat brain sections. [3H]TAK-063 accumulation in the CPu was more than eighteen-fold higher than that in the Hipp and Amy. TAK-063 at 0.3mg/kg increased the blood oxygenation level-dependent (BOLD) signal in the striatum and Amy, and decreased it in the Fcx in a phMRI study with anesthetized rats. ⋯ TAK-063 at 0.2mg/kg (35% PDE10A occupancy in monkeys) also reduced the ketamine-induced increase in EEG gamma power in awake monkeys. In line with the EEG data, TAK-063 at 0.3mg/kg reversed the ketamine-induced BOLD signal changes in the cortex, Bs, and Cb in a phMRI study with anesthetized rats. These data suggest that TAK-063 at about 30% PDE10A occupancy modulates activities of multiple brain regions through activation of neuronal circuits in rats and monkeys.
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Muscle fatigue modifies the gain between motor command magnitude and the mechanical muscular response. In other words, post-fatigue, central drives to the muscles must increase to maintain a particular submaximum mechanical output. In this study, we tested the hypothesis that this modified gain can be predicted by the central nervous system (CNS) during discrete ballistic movements. ⋯ All these results support that fatigue effects are taken into account during movement planning. Indeed, given that no feedback could enable participants to adjust acceleration during movement, this capacity to anticipate fatigue effects is the exclusive result of feedforward processes. To account for this prediction capacity, we discuss the role of fatigue-related modifications in sensory inputs from the working muscles.
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Absence seizures arise from disturbances within the corticothalamocortical network, however the precise cellular and molecular mechanisms underlying seizure generation arising from different genetic backgrounds are not fully understood. While recent experimental evidence suggests that changes in inhibitory microcircuits in the cortex may contribute to generation of the hallmark spike-wave discharges, it is still unclear if altered cortical inhibition is a result of interneuron dysfunction due to compromised glutamatergic excitation and/or changes in cortical interneuron number. The stargazer mouse model of absence epilepsy presents with a genetic deficit in stargazin, which is predominantly expressed in cortical parvalbumin-positive (PV(+)) interneurons, and involved in the trafficking of glutamatergic AMPA receptors. ⋯ Further analysis using confocal fluorescence microscopy revealed that although there are no changes in cortical PV(+) interneuron number, there is a predominant loss of GluA1 and 4 containing AMPA receptors in PV(+) neurons in stargazers compared to non-epileptic controls. Taken together, these data suggest that the loss of AMPA receptors in PV(+) neurons could impair their feed-forward inhibitory output, ultimately altering cortical network oscillations, and contribute to seizure generation in stargazers. As such the feed-forward inhibitory interneurons could be potential targets for future therapeutic intervention for some absence epilepsy patients.
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Spinal lamina I projection neurons serve as a major conduit by which noxious stimuli detected in the periphery are transmitted to nociceptive circuits in the brain, including the parabrachial nucleus (PB) and the periaqueductal gray (PAG). While neonatal spino-PB neurons are more than twice as likely to exhibit spontaneous activity compared to spino-PAG neurons, the underlying mechanisms remain unclear since nothing is known about the voltage-independent (i.e. 'leak') ion channels expressed by these distinct populations during early life. To begin identifying these key leak conductances, the present study investigated the role of classical inward-rectifying K(+) (Kir2) channels in the regulation of intrinsic excitability in neonatal rat spino-PB and spino-PAG neurons. ⋯ In addition, voltage-clamp experiments showed that spino-PB and spino-PAG neurons express similar amounts of Kir2 current during the early postnatal period, suggesting that the differences in the prevalence of spontaneous activity between the two populations are not explained by differential expression of Kir2 channels. Overall, the results indicate that Kir2-mediated conductance tonically dampens the firing of multiple subpopulations of lamina I projection neurons during early life. Therefore, Kir2 channels are positioned to tightly shape the output of the immature spinal nociceptive circuit and thus regulate the ascending flow of nociceptive information to the developing brain, which has important functional implications for pediatric pain.