Neuroscience
-
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.
-
Brain ischemic tolerance is an endogenous protective mechanism activated by a preconditioning stimulus that is closely related to N-methyl-d-aspartate receptor (NMDAR). Glycine transporter type 1 (GlyT-1) inhibitors potentiate NMDAR and suggest an alternative strategy for brain preconditioning. The aim of this work was to evaluate the effects of brain preconditioning induced by sarcosine, a GlyT-1 inhibitor, against global cerebral ischemia and its relation to NMDAR. ⋯ The expression of glycine receptors and the NR1 and NR2A subunits of NMDAR were not affected by sarcosine preconditioning. However, sarcosine preconditioning reduced the expression of the NR2B subunits of NMDAR. In conclusion, these data demonstrate that sarcosine preconditioning induces ischemic tolerance against global cerebral ischemia and this neuroprotective state is associated with changes in glycine transport and reduction of NR2B-containing NMDAR expression.
-
Physical exercise could exert a neuroprotective effect in both clinical studies and animal experiments. A series of related studies have indicated that physical exercise could reduce infarct volume, alleviate neurological deficits, decrease blood-brain barrier dysfunction, promote angiogenesis in cerebral vascular system and increase the survival rate after ischemic stroke. ⋯ Furthermore, it was demonstrated that exercise training could decrease the blood-brain barrier dysfunction and promote angiogenesis in cerebral vascular system. An awareness of the exercise intervention benefits pre- and post stroke may lead more stroke patients and people with high-risk factors to accept exercise therapy for the prevention and treatment of stroke.
-
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.