Neuroscience
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The ventral hippocampus is a component of the neural circuitry involved with context-associated memory for reward and generation of appropriate behavioral responses to context. Glycogen synthase kinase 3 beta (GSK3β) has been linked to the maintenance of synaptic plasticity, contextual memory retrieval, and is involved in the reconsolidation of cocaine-associated contextual memory. In this study, the effects of targeted downregulation of GSK3β in the ventral hippocampus were examined on a series of behavioral tests for assessing drug reward-context association and non-reward related memory. ⋯ Impaired object location memory was observed in mice with GSK3β downregulation in the ventral hippocampus, but novel object recognition remained intact. These results indicate that GSK3β signaling in the ventral hippocampus is differentially involved in the formation of place-drug reward association dependent upon drug class. Additionally, ventral hippocampal GSK3β signaling is important in detection of discrete spatial cues, but not recognition memory for objects.
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In several tauopathies such as Alzheimer's disease (AD), an increased incidence of seizures is observed. Tau, one of the major proteins implicated in AD pathology, is an important regulator of neural network excitability and might participate in the underlying epileptic cascade. However, the mechanisms underlying this relationship are not fully elucidated. ⋯ Also, age-related differences in susceptibility could be demonstrated for both genotypes. Identification and targeting of secondary diseases such as epilepsy, which aggravate dementia and lead to earlier institutionalization, is key. This study finds that tau pathology itself is sufficient to alter seizure susceptibility in a rodent model, indicating that the disease process is crucial in the emergence of epilepsy in patients with tauopathy.
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The neural mechanisms associated with the limited capacity of working memory (WM) has long been studied, but it is still unclear which neural regions are associated with the precision of visual WM. Here, an orientation recall task for estimating the trial-wise precision of visual WM was performed and then repeated two weeks later in an fMRI scanner. Results showed that activity in frontal and parietal regions during WM maintenance scaled with WM load, but not with the precision of WM (i.e., recall error in radians). ⋯ Interestingly, a region within the prefrontal cortex, the inferior frontal junction (IFJ), exhibited greater functional connectivity with LOC when the WM load increased. Together, our findings provide unique evidence that the LOC supports visual WM precision, while communication between the IFJ and LOC varies based on WM load demands. These results suggest an intriguing possibility that distinct neural mechanisms may be associated with general content (load) or detailed information (precision) of WM.
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In certain neurons, zinc ions are stored in synaptic vesicles by zinc transporter 3 (ZnT3). Vesicular zinc can then be released synaptically to modulate myriad targets. In vitro evidence indicates that these targets may include brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB). ⋯ BDNF protein levels increased with age in female mice but not in males. And in females, but not males, ZnT3 KO mice exhibited great hippocampal BDNF mRNA expression than wild type mice. We conclude that, at least in naïve mice housed under standard laboratory conditions, elimination of vesicular zinc does not affect BDNF or TrkB protein levels.
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The gene associated with retinoid-interferon-induced mortality-19 (GRIM-19) plays several significant roles in cellular processes, including ATP synthesis, reactive oxygen species formation, and the regulation of glycolytic enzyme activity, which are closely related to the pathophysiological mechanisms of epilepsy. Therefore, we investigated the expression pattern of GRIM-19 in the CA1 area of the hippocampus in 8-week-old male C57BL/6 mice following pilocarpine-induced status epilepticus (SE). Neuronal death in the hippocampal CA1 area was prominently observed at 4 and 7 days after SE, and astrocytes and microglia became progressively activated beginning at 1 day after SE. ⋯ Moreover, we observed that both GRIM-19 and pyruvate kinase isozyme M2, a glycolytic enzyme, were highly expressed in reactive astrocytes after SE. These results indicate that expression of GRIM-19 in the hippocampus is mainly observed in neurons under normal conditions but is altered in the SE mouse model as evidenced by its increased expression in reactive astrocytes. The possible role of GRIM-19 in the glycolytic activity of reactive astrocytes is also discussed.