Neuroscience
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Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a transcriptional coactivator known to regulate gene programs in a cell-specific manner in energy-demanding tissues, and its dysfunction has been implicated in numerous neurological and psychiatric disorders. Previous work from the Cowell laboratory indicates that PGC-1α is concentrated in inhibitory interneurons and is required for the expression of the calcium buffer parvalbumin (PV) in the cortex; however, the impact of PGC-1α deficiency on inhibitory neurotransmission in the motor cortex is not known. Here, we show that mice lacking PGC-1α exhibit increased amplitudes and decreased frequency of spontaneous inhibitory postsynaptic currents in layer V pyramidal neurons. ⋯ Furthermore, PV-positive interneurons in PGC-1α -/- mice display reductions in intrinsic excitability and excitatory input without changes in gross interneuron morphology. Taken together, these data show that PGC-1α is required for normal inhibitory neurotransmission and cortical PV-positive interneuron function. Given the pronounced motor dysfunction in PGC-1α -/- mice and the essential role of PV-positive interneurons in maintenance of cortical excitatory:inhibitory balance, it is possible that deficiencies in PGC-1α expression could contribute to cortical hyperexcitability and motor abnormalities in multiple neurological disorders.
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Necker cube is one of the ambiguous figures that is physically a static image but can be alternately perceived in two different perspectives. A great deal of debate exists regarding ambiguous figures that induce spontaneous switching between rival percepts. To investigate the time course of neural processes underlying such perceptual rivalry, we recorded electroencephalograms associated with participants' perceptions of a Necker cube under ambiguous and unambiguous conditions, using a modified discontinuous-presentation method. ⋯ We compared endogenous reversal activity of ambiguous stimuli with exogenous reversals. As a result, we found that the right-occipital beta-band activity (16-26 Hz) increased 100-150 ms and 350-450 ms after the onset of the ambiguous stimulus only when the perception of the ambiguous stimulus differed from that of the first stimulus. These results indicate that activity in the right-occipital total beta band reflects endogenous switching between rivaling percepts.
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The primary limitation of thrombolytic treatment of ischemic stroke with tissue plasminogen activator (tPA) is the hemorrhagic risk. We tested AcSDKP (N-acetyl-seryl-aspartyl-lysyl-proline), as an auxiliary therapeutic agent, to reduce blood-brain barrier (BBB) disruption in a combination tPA thrombolytic treatment of stroke. Wistar rats subjected to embolic stroke were randomly assigned to either the tPA monotherapy group (n=9) or combination of tPA and AcSDKP treatment group (n=9) initiated at 4 h after ischemia. ⋯ The substantial reduction of BBB leakage observed in the combination treatment group was closely associated with reduced ischemic lesions measured by T2 maps (113.6±24.9 mm3 vs. 188.1±60.8 mm3, p<0.04 at 6 days). Histopathological analysis of the same population of rats showed that the combination treatment significantly reduced parenchymal fibrin deposition (0.063±0.059 mm2 vs. 0.172±0.103 mm2, p<0.03) and infarct volume (146.7±35.9 mm3 vs. 199.3±60.4 mm3, p<0.05) compared to the tPA monotherapy at 6days after stroke. MRI provides biological insight into the therapeutic benefit of combination treatment of stroke with tPA and AcSDKP 4h after onset, and demonstrates significantly improved cerebrovascular integrity with neuroprotective effects compared with tPA monotherapy.
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The N2 subcomponents of event-related potentials are known to reflect early attentional processes. The anterior N2 may reflect conflict monitoring, whereas the posterior N2 may be involved in target detection. The aim of this study was to identify the brain areas involved in the generation of the N2 subcomponents, in order to define the spatiotemporal dynamics of these attentional processes. ⋯ Common N2 generators were observed in the Brodmann area (BA) 24 of the anterior cingulate cortex (ACC). The posterior cingulate cortex and the central precuneus were more involved in distracter processing, whereas the anterior precuneus and BA 32 of the ACC were target-specific. In accordance with previous demonstration of the frontoparietal cortex's critical role in attentional processes, these new data shed light on the ACC's role in conflict monitoring and its interaction with other median and frontoparietal structures in early attentional processes.
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Efficient sensory processing of the environment is a critical function for any organism to survive and is accomplished by having neurons adapt their responses to stimuli based on behavioral context in part through neuromodulators such as serotonin (5-HT). We have recently shown that one critical function of the serotonergic system in weakly electric fish is to enhance sensory pyramidal neuron responses within the electrosensory lateral line lobe (ELL) to stimuli caused by same sex conspecifics, thereby enhancing their perception. This enhancement is accomplished by making pyramidal neurons more excitable through downregulation of potassium channels. ⋯ Indeed, 5-HT application subsequent to ket application did not cause any significant changes in neuron excitability and responses to current injection. We further show that ket applied in vivo can block the effects of 5-HT on behavioral responses. Thus, our results strongly suggest that the previously observed effects of 5-HT on sensory processing within ELL and their consequences for behavior are mediated by 5-HT2 receptors.