Neuroscience
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Status epilepticus (SE) is a life-threatening condition needing immediate care to prevent brain damage. SE with electrographic and behavioral features similar to those seen in humans is reproduced in rodents by i.p. pilocarpine injection, and can be terminated by diazepam and ketamine treatment but only behaviourally, not electrographically. Little is known on the behavioral and EEG effects induced by a delayed administration of ketamine (25 mg/kg) after diazepam (10 mg/kg) or vice versa. ⋯ However, diazepam administration before ketamine significantly shortened the time of behavioral recovery compared to when ketamine was administered before diazepam (p < 0.05). The two protocols were also associated to distinct EEG changes in gamma and high frequency oscillations. In conclusion, although diazepam and ketamine are not effective in stopping EEG SE, diazepam administration one hour before ketamine shortens behavioral recovery in pilocarpine-treated mice.
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Paired-pulse transcranial magnetic stimulation (ppTMS) has been used extensively to probe local facilitatory and inhibitory function in motor cortex. We previously developed a reliable ppTMS method to investigate these functions in visual cortex and found reduced thresholds for net intracortical inhibition compared to motor cortex. The current study used this method to investigate the temporal dynamics of local facilitatory and inhibitory networks in visual cortex in 28 healthy subjects. ⋯ Intervals of 50-200 ms exhibited statistically significant suppression of phosphenes, however, suppression was not uniform with some subjects demonstrating no change or facilitation. This study demonstrates that the temporal dynamics of local inhibitory and facilitatory networks are different across motor and visual cortex and that optimal parameters to index local inhibitory and facilitatory influences in motor cortex are not necessarily optimal for visual cortex. We refer to the observed inhibition as visual cortex inhibition (VCI) to distinguish it from the phenomenon reported in motor cortex.
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Evidence suggests that cerebrovascular hemodynamic disturbances underlie cognitive deterioration secondary to cardiovascular disease (CVD), including manifestations other than stroke, but the mechanisms remain unclear. To date, the majority of studies have used neuropsychological measures validated for the detection of clinically significant cognitive decline but lack the sensitivity to accurately detect subclinical or subtle cognitive changes. The N2 and P3 components of the event-related potential are sensitive markers of attention and cognitive processing, and are valuable in the assessment of age-related cognitive changes and neurodegenerative disease. ⋯ Further, MCAv and PI were strongly associated with N2 amplitude in the CVD group, such that greater MCAv was associated with reductions in N2 amplitude (b = -0.58, p = .018), whilst PI was associated with increases in N2 amplitude (b = 0.66, p = .006). No relationships between MCAv or PI with N2 or P3 ERP components were observed in the healthy control group. The data reported here suggest that a reduction in N2 amplitude may be an important objective indicator of subclinical cognitive and attentional alterations in non-stroke CVD, and support the notion that cerebrovascular hemodynamic disturbances play a role in the pathogenesis of cognitive deterioration secondary to non-stroke CVD.
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The floor plate of the developing midbrain gives rise to dopaminergic (DA) neurons, an important class of cells involved in Parkinson's disease (PD). Neural progenitors of the midbrain floor plate utilize key genes in transcriptional networks to drive dopamine neurogenesis. Identifying factors that promote dopaminergic neuron transcriptional networks can provide insight into strategies for therapies in PD. ⋯ We then showed that overexpression of Nato3 in the developing chick mesencephalon produces a regionally dependent increase in genes associated with the DA neurogenesis, (such as Foxa2, Lmx1b and Shh) as well as DA neuron genes Nurr1 (an immature DA neuron marker) and mRNA expression of tyrosine hydroxylase (TH, a mature DA neuron marker). Interestingly, our data also showed that Nato3 is a potent regulator of Lmx1b by its broad induction of Lmx1b expression in neural progenitors of multiple regions of the CNS, including the midbrain and spinal cord. These data introduce a new, in vivo approach to identifying a gene that can drive DA transcriptional networks and provide the new insight that Nato3 can drive expression of key DA neuron genes, including Lmx1b, in neural progenitors.
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Calcium (Ca2+) is an essential component in intracellular signaling of brain cells, and its control mechanisms are of great interest in biological systems. Ca2+ can signal differently in neurons and glial cells using the same intracellular pathways or cell membrane structural components. These types of machinery are responsible for entry, permanence, and removal of Ca2+ from the cellular environment and are of vital importance for brain homeostasis. This review highlights the importance of Ca2+ in neuronal and glial cell physiology as well as aspects of learning, memory, and Alzheimer's disease, focusing on the involvement of L-type voltage-gated Ca2+ channels.