Neuroscience
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Many studies have implicated hippocampal dysregulation in the pathophysiology of alcohol use disorder (AUD). However, over the past twenty years, a growing body of evidence has revealed distinct functional roles of the dorsal (dHC) and ventral (vHC) hippocampal subregions, with the dHC being primarily involved in spatial learning and memory and the vHC regulating anxiety- and depressive-like behaviors. Notably, to our knowledge, no rodent studies have examined the effects of chronic ethanol exposure on synaptic transmission along the dorsal/ventral axis. ⋯ Extracellular recordings revealed marked CIE-associated increases in synaptic excitation in the CA1 region that were exclusively restricted to the ventral domain of the hippocampus. Western blot analysis of synaptoneurosomal fractions revealed that the expression of two proteins that regulate synaptic strength, GluA2 and SK2, were dysregulated in the vHC, but not the dHC, following CIE. Together, these findings suggest that the ventral CA1 region may be particularly sensitive to the maladaptive effects of chronic ethanol exposure and provide new insight into some of the neural substrates that may contribute to the negative affective state that develops during withdrawal.
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Dravet syndrome (DS) is a disease that is primarily caused by the inactivation of the SCN1A-encoded voltage-gated sodium channel alpha subunit (Nav1.1). In this study, we constructed an SCN1A gene knockout model using CRISPR/Cas9 genome editing technology to deprive the Nav1.1 function in vitro. ⋯ We also noticed changes in the spliceosome, decreased glycolytic capacity, disturbances in calcium signaling pathways, and changes in the potassium, sodium, chloride, and calcium plasma channels after SCN1A knockout. In this study, we have been the first time to discover these changes and summarize them here and hope it would provide some clue for the study of Nav1.1 in the nervous system.
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The α3 Na+,K+-ATPase (α3NKA) is one of four known α isoforms of the mammalian transporter. A deficiency in α3NKA is linked to severe movement control disorders. Understanding the pathogenesis of these disorders is limited by an incomplete knowledge of α3NKA expression in the brain as well as the challenges associated with identifying living cells that express the isoform for subsequent electrophysiological studies. ⋯ Fluorescence was not detected in astrocytes or white matter areas. ZsGreen1-positive neurons were readily observed in fresh (unfixed) brain sections, which were amenable to patch-clamp recordings. Thus, the α3NKA-ZsGreen1 mouse model provides a powerful tool for studying the distribution and functional properties of α3NKA-expressing neurons in the brain.
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Previous studies have revealed that sleep deprivation (SD) alters hippocampal functional connectivity (FC). However, the effects of SD on the FC of hippocampal subregions are still unknown. In this study, we used a masked independent component analysis (mICA) to partition the hippocampus into several small regions and investigated the changes in the FC of each small region within the whole brain after 24 h of SD in 40 normal young subjects. ⋯ The FC between the left posterior of the anterolateral and the left lateral posterior of the anterior hippocampal regions and somatomotor network changed more negative after SD. However, increased FC was identified between the left middle hippocampal region and vision-related regions after SD. Our results reflect differential effects of SD on the FC in specific hippocampal regions and provide new insights into the impact of SD on the resting-state functional organization in the human brain.
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Fragile X Syndrome (FXS) is a leading genetic cause of autism and intellectual disabilities. Sensory-processing deficits are common in humans with FXS and an animal model, the Fmr1 knockout (KO) mouse, manifesting in the auditory system as debilitating hypersensitivity and abnormal electroencephalographic (EEG) and event-related potential (ERP) phenotypes. FXS is a neurodevelopmental disorder, but how EEG/ERP phenotypes change during development is unclear. ⋯ Genotype differences in stimulus-evoked gamma power were present in both cortical regions, but the direction and strength of the changes were age-dependent. These findings suggest that cortical deficits are present during early development and may contribute to sensory-processing deficits in FXS, which in turn may lead to anxiety and delayed language. Developmental changes in EEG measures indicate that observations at a single time-point during development are not reflective of FXS disease progression and highlight the need to identify developmental trajectories and optimal windows for treatment.