Neuroscience
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Given the fact that both melatonin and nicotinamide mononucleotide (NMN) act as pleiotropic agents in various age-related cognitive disorders, we aimed to investigate the effect of these compounds separately and together on the cognitive outcomes, mitochondrial function, and apoptosis in aged rats. Forty old and ten young (24 and 3 months old, respectively) male Wistar rats were randomly allocated into five groups: Young+Normal saline (NS), Aged+NS, Aged+Melatonin, Aged+NMN, and Aged+melatonin+NMN. Melatonin (10 mg/kg) and NMN (100 mg/kg) were administered, separately or in combination for 28 every other day in aged animals. ⋯ Behavioral results revealed that NMN and melatonin separately or in combination, alleviate aging-induced memory impairment. Moreover, agents' co-administration declined mitochondrial dysfunction and apoptotic cell count both in PFC and HIP regions. The agents separately or in combination (more potent) could induce neuroprotective effect and improve learning and memory in aged animals.
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The human capability to learn new motor skills depends on the efficient engagement of cognitive-motor resources, as reflected by mental workload, and psychological mechanisms (e.g., self-efficacy). While numerous investigations have examined the relationship between motor behavior and mental workload or self-efficacy in a performance context, a fairly limited effort focused on the combined examination of these notions during learning. Thus, this study aimed to examine their concomitant dynamics during the learning of a novel reaching skill practiced throughout multiple sessions. ⋯ However, as the performance becomes more automatic, a lower level of mental workload is attained driven by decreased recruitment of attentional resources. These available resources allow for a reliable assessment of self-efficacy resulting in a subsequent observable change. These results are also discussed in terms of the application to the training and design of assistive technologies.
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Stress, a major precipitant of depression, and antidepressants have major impact on synaptic integrity and plasticity in brain areas, such as hippocampus (HPC) and prefrontal cortex (PFC). We have recently shown that, unlike Wistar rats, rats of the Wistar-Kyoto (WKY) strain fail to respond to chronic antidepressant treatment after exposure to chronic mild stress (CMS) procedure. However, deep brain stimulation (DBS) of PFC was effective in both strains. ⋯ Some other changes in gene expression were identified in dorsal HPC and PFC, particularly in Wistars, that were not normalized by DBS. No effects were identified that were common to both Wistars and WKY. The difference between Wistars and WKY in the balance of overall gene expression in HPC may be relevant to the resistance of WKY rats to antidepressant drug treatment.
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Models of basal ganglia (BG) function predict that tonic inhibitory output to motor thalamus (MT) suppresses unwanted movements, and that a decrease in such activity leads to action selection. Further, for unilateral activity changes in the BG, a lateralized effect on contralateral movements can be expected due to ipsilateral thalamocortical connectivity. However, a direct test of these outcomes of thalamic inhibition has not been performed. ⋯ In confirmation of model predictions, we found that unilateral optogenetic inhibition of GABAergic output from the SNr, during ipsilaterally cued trials, biased decision making towards a contralateral lick without affecting motor performance. In contrast, optogenetic excitation of SNr terminals in MT resulted in an opposite bias towards the ipsilateral direction confirming a bidirectional effect of tonic nigral output on directional decision making. However, direct optogenetic excitation of neurons in the SNr resulted in bilateral movement suppression, which is in agreement with previous results that show such suppression for nigral terminals in the superior colliculus (SC), which receives a bilateral projection from SNr.
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Several reports of augmented hyperpolarisation-activated cyclic nucleotide-gated (HCN) currents in seizures have suggested a pro-convulsive identity for HCN channels. The mutations identified in one or more of the four HCN channel subunits are found to be contributing to different epileptic phenotypes. S126L, S632W, V246M and E515K are four different mutations affecting the HCN2 subunit and have been reported in febrile seizures and partial/generalised idiopathic epilepsies. ⋯ Their effects on excitability were studied by observing resting membrane potentials, input resistances and plasticity profiles for measuring the sliding modification threshold (SMT) of Bienenstock-Cooper-Munro (BCM) theory. Virtual knockouts of ion channels other than HCN were also performed to assess their role in altering excitability when they act alongside HCN2 mutations. Our results show that HCN2 mutations can potentially be a primary causative factor for excessive action potential firing through their effect on resting membrane potentials and input resistance.