Neuroscience
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Chronic intermittent alcohol (CIA) exposure produces altered motivational states characterized by anxiety and escalated alcohol consumption during withdrawal. The endocannabinoid (ECB) system contributes to these symptoms, and sex differences in alcohol dependence, as well as bidirectional interactions between ECBs and gonadal hormones have been documented. Thus, we evaluated sex differences in alcohol consumption, anxiety-like behavior, and ECB mRNA expression in the nucleus accumbens (NAc) of alcohol-dependent rats during acute withdrawal. ⋯ Neither E2 nor CIA altered alcohol consumption in OVX females. However, E2 reduced both DAGLα and MAGL mRNA, suggesting that E2 may influence the biosynthesis and degradation of 2-arachidonoylglycerol (2-AG) in the NAc. Collectively, these studies indicate sexual dimorphism in alcohol consumption in non-dependent rats and suggest that E2-mediated alterations in NAc ECB mRNA expression during withdrawal may be a mechanism by which sex differences in alcohol dependence emerge.
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The autosomal recessive Hereditary Motor and Sensory Neuropathy with Agenesis of the Corpus Callosum (HMSN/ACC) is associated with the dysfunction of the K(+)-Cl(-) cotransporter type 3 (KCC3), which is an electroneutral cotransporter. We previously found that the inhibition of KCC3 cotransporter activity reduces the propagation of action potentials in the peripheral nervous system (PNS). However, the pathogenesis by which KCC3 deficiency impairs peripheral nerve function remains to be examined. ⋯ However, electrophysiological studies using the threshold tracking technique indicated a reduced stimulus-response curve slope with an elevated rheobase, a decreased strength-duration time constant, diminished persistent Na(+) currents, and an outward deviation of threshold electrotonus in KCC3(-/-) nerves compared to wild-type nerves. These functional changes indicate an overall reduction in axonal excitability and suggest an increase in paranodal conductance, which was relevant to the pathology at the paranode. Altogether, our findings highlight the importance of KCC3 in maintaining paranodal integrity and in optimizing the propagation of action potentials along peripheral nerves.
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The rhythmic activity of motoneurons (MNs) that underlies locomotion in mammals is generated by synaptic inputs from the locomotor network in the spinal cord. Thus, the quantitative estimation of excitatory and inhibitory synaptic conductances is essential to understand the mechanism by which the network generates the functional motor output. Conductance estimation is obtained from the voltage-current relationship measured by voltage-clamp- or current-clamp-recording with knowledge of the leak parameters of the recorded neuron. ⋯ Next, the conductance variations were estimated from mouse spinal MNs in vitro during drug-induced-locomotor-like activity. We found that the peak of excitatory conductance occurred during the depolarizing phase of the locomotor cycle, whereas the peak of inhibitory conductance occurred during the hyperpolarizing phase. These results suggest that the locomotor-like activity is generated by push-pull modulation via excitatory and inhibitory synaptic inputs.
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Internet-searching behaviors may change ways in which we find, store and consider information. In this study, we tested the effect of short-term Internet-search practicing on recollection processes. Fifty-nine human subjects with valid data (Experimental group, 43; Control group, 16) completed procedures involving a pre-test, 6days of practicing, and a post-test. ⋯ During imaging and as compared to pre-test data, subjects in the experimental group showed during post-test recall relatively decreased brain activations bilaterally in the middle frontal and temporal gyri. Such findings were not observed in the control group. The findings suggest that six days of practicing Internet searching may improve the efficiency of Internet searching without influencing the accuracy of recollection, with neuroimaging results implicating cortical regions involved in long-term memory and executive processing.
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Microinjection of morphine into the periaqueductal gray (PAG) produces antinociception. In vitro slice recordings indicate that all PAG neurons are sensitive to morphine either by direct inhibition or indirect disinhibition. We tested the hypothesis that all PAG neurons respond to opioids in vivo by examining the extracellular activity of PAG neurons recorded in lightly anesthetized and awake rats. ⋯ Changes in activity caused by morphine were surprisingly modest (a median increase from 0.7 to 1.3Hz). The small inconsistent effects of morphine are in stark contrast to the large changes produced by morphine on the activity of rostral ventromedial medulla (RVM) neurons or the widespread inhibition and excitation of PAG neurons treated with opioids in in vitro slice experiments. The relatively modest effects of morphine in the present study suggest that morphine produces antinociception by causing small changes in the activity of many PAG neurons.