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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Organophosphorus (OP) compounds are deadly chemicals that exert their intoxicating effects through the irreversible inhibition of acetylcholinesterase (AChE). In addition to an excess of peripheral ailments, OP intoxication induces status epilepticus (SE) which if left untreated may lead to permanent brain damage or death. Benzodiazepines are typically the primary therapies for OP-induced SE, but these drugs lose efficacy as treatment time is delayed. ⋯ FJB staining demonstrated that none of the tested drugs had widespread neuroprotective abilities. Overall these data suggest that neurosteroids may represent the most promising anticonvulsant option for OP-induced SE out of the seven unique mechanisms tested here. Additionally, these results suggest that drugs that provide significant neuroprotection from OP-induced SE without some degree of anticonvulsant activity are elusive, which further highlights the necessity to continue screening novel adjunct treatments through the CNS program.
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High gamma activity (HGA) of verbal-memory encoding using invasive-electroencephalogram has laid the foundation for numerous studies testing the integrity of memory in diseased populations. Yet, the functional connectivity characteristics of networks subserving these memory linkages remains uncertain. ⋯ The HGA-memory network comprised regions from both the cognitive control and primary processing networks, validating that effective verbal-memory encoding requires integrating brain functions, and is not dominated by a central cognitive core. Our results demonstrate a tonic intrinsic set of functional connectivity, which provides the necessary conditions for effective, phasic, task-dependent memory encoding.
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The effects of muscle fatigue are known to be altered in older adults, and age-related changes in the brain are likely to be a contributing factor. However, the neural mechanisms underlying these changes are not known. The aim of the current study was to use transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) to investigate age-related changes in cortical excitability with muscle fatigue. ⋯ For TMS-EEG, the amplitude of the P30 and P180 potentials were unaffected by fatigue in older participants (P > 0.05). In contrast, the amplitude of the N45 potential in older adults was significantly reduced both during (positive cluster: mean voltage difference = 0.7 µV, P < 0.005; negative cluster: mean voltage difference = 0.9 µV, P < 0.0005) and after (mean voltage difference = 0.5 µV, P < 0.005) fatiguing exercise, whereas this response was absent in young participants. These results suggest that performance of maximal intermittent isometric exercise in old but not young adults is associated with modulation of cortical inhibition likely mediated by activation of gamma-aminobutyric acid type A receptors.