Neuroscience
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Substance use disorders (SUD) often co-occur with other mental disorders such as major depression (MD). Our previous findings revealed sex-dependent changes in extracellular levels of glutamate (Glu) and glutamine (Gln) in the nucleus accumbens (NAc) in Long-Evans rats that were exposed to 21 days of chronic social defeat stress (CSDS), which models MD. The current study investigated the role of a Gln transporter called sodium-coupled neutral amino acid transporter subtype 1/2 (SNAT 1/2), phosphate-activated glutaminase (PAG), and astrocytic glutamate transporter-1 (GLT-1) on CSDS animals exposed to cocaine. ⋯ Additionally, both PAG and GLT-1 levels were increased in the PFC in CSDS males. On the other hand, cocaine reduced SNAT 1/2 and GLT-1 levels in the NAc and PFC in CSDS females. Our results show that CSDS altered locomotor responses upon cocaine exposure in a sex-dependent manner that may be mediated by molecules associated with the Glu-Gln transfer.
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The central executive system (CES) may be the most fundamental yet least understood component of working memory. There is an ongoing debate about which brain regions underlie the top-down regulation of CES during working memory tasks. The neural substrates and regulatory mechanisms of CES remain controversial partly because few previous studies have been focused on comprehensive activation and deactivation joint analysis on all systems involved in all working memory stages, which have shown increasing importance in depicting the neural configuration of working memory. ⋯ We assessed brain activity during various working memory stages using general linear model and single trial-stage estimation, and examined the relationship between the single trial-stage activity and behavioral performance. We identified constant activation in the dorsal anterior cingulate cortexand anterior insula in all working memory stages and its relationship with performance, which indicate the CES's neural basis. We also identified dynamic configuration of multiple downstream systems in different working memory stages, which indicates the regulation mechanism of CES.
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Motor function can be modulated by transcranial alternating current stimulation (tACS) in alpha, beta, and high-gamma frequencies. However, few studies have investigated tACS-induced behavioral changes in combination with endogenous oscillatory neural activity in detail. Herein, we investigated the effect of tACS on motor learning capacity and endogenous oscillatory neural activity. ⋯ Oscillation analysis revealed a significant increase in beta-band power after 70-Hz tACS but not in the other stimulation groups. Our finding that capacity for motor learning and endogenous oscillatory beta activity were modulated in parallel after 70-Hz tACS suggests that 70-Hz tACS may increase the motor learning capacity by cross-modulating beta oscillatory activity. Because high gamma and beta oscillatory activity have been shown to reflect the activity of excitatory and inhibitory interneuron, our results may derive from the modulation of excitatory and inhibitory interneurons in M1 by 70-Hz tACS.
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Hepatic ischemia reperfusion (HIR) has been found to induce hippocampus injury and cognitive dysfunction. The N-methyl-d-aspartate (NMDA) receptor subunit 2A (NR2A) is an important factor mediating excitotoxicity and neurons injury, and autophosphorylation of Src can up-regulate tyrosine phosphorylation of NR2A to improve its activity. However, the role of Src and NR2A in HIR-induced hippocampus injury in young mice remains unknown. ⋯ Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ) and interleukin (IL)-6 were increased after reperfusion of 3 days, while PP2 and NVP-AAM077 treatment didn't attenuate the changes. And no difference was found in serum TNF-α, IFN-γ, IL-6 concentrations as well as the levels of Src, p-Src, NR2A, p-NR2A, PSD95 among the four groups after reperfusion of 1 month. In summary, HIR can lead to hippocampus injury and long-term cognitive dysfunction, and Src-PSD95-NR2A pathway plays an important role in the process.
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The olfactory circuitry in mice involves a well-characterized, vertical receptor type-specific organization, but the localized inhibitory effect from granule cells on action potentials that propagate laterally in secondary dendrites of mitral cell remains open to debate. To understand the functional dynamics of the lateral (horizontal) circuits, we analyzed odor-induced signaling using transgenic mice expressing a genetically encoded Ca2+ indicator specifically in mitral/tufted and some juxtaglomerular cells. Optical imaging of the dorsal olfactory bulb (dOB) revealed specific patterns of glomerular activation in response to odor presentation or direct electric stimulation of the olfactory nerve (ON). ⋯ To test whether the widespread odor response component represented signal propagation along mitral cell secondary dendrites, an NMDA receptor antagonist alone was applied to the dOB and was found to also increase and expand odor-evoked response patterns. Finally, with dOB excitatory synaptic transmission completely blocked, application of 1 mM muscimol (a GABAA receptor agonist) to a circumscribed volume in the deep external plexiform layer (EPL) induced an odor non-responsive area. These results indicate that odor stimulation can activate olfactory reciprocal synapses and control lateral interactions among olfactory glomerular modules along a wide range of mitral cell secondary dendrites by modulating the inhibitory effect from granule cells.