GRP or bicuculline (a γ-aminobutyric acidA antagonist) administered near the SON during the early night elicited phase delays of circadian activity rhythms. These data suggest that GRP-induced phase-resetting is dependent on levels of glutamatergic and serotonergic neurotransmission in the SCN and implicate activity in the SON as a potential regulator of photic signaling in the SCN. “
“Speech motor control develops gradually as the acoustics of speech are mapped onto the positions and movements of the articulators. PLX4032 clinical trial In this event-related potential (ERP) study, children and adults aged 4–30 years produced vocalizations while exposed to frequency-altered feedback. Vocal pitch variability
and the latency of vocal responses were found to differ as a function of age. ERP responses indexed by the P1–N1–P2 complex were also modulated as a function of age. P1 amplitudes decreased with age, whereas N1 and P2 amplitudes increased with age. In addition, a correlation between vocal variability and N1 amplitudes was found, suggesting a complex interaction EPZ-6438 chemical structure between behavioural and neurological responses to frequency-altered feedback. These results suggest that the neural systems that integrate auditory feedback during vocal motor control undergo robust changes with age and physiological development. “
“A major source of energy demand in neurons is the Na+/K+-ATPase pump that restores the ionic gradient across the plasma membrane subsequent to depolarizing neuronal
activity. The energy comes primarily from mitochondrial oxidative metabolism, of which cytochrome c oxidase
(COX) is a key enzyme. Recently, we found that all 13 subunits of COX are regulated by specificity (Sp) factors, and that the neuron-specific Metformin in vivo Sp4, but not Sp1 or Sp3, regulates the expression of key glutamatergic receptor subunits as well. The present study sought to test our hypothesis that Sp4 also regulates Na+/K+-ATPase subunit genes in neurons. By means of multiple approaches, including in silico analysis, electrophoretic mobility shift and supershift assays, chromatin immunoprecipitation, promoter mutational analysis, over-expression, and RNA interference studies, we found that Sp4, with minor contributions from Sp1 and Sp3, functionally regulate the Atp1a1, Atp1a3, and Atp1b1 subunit genes of Na+/K+-ATPase in neurons. Transcripts of all three genes were up-regulated by depolarizing KCl stimulation and down-regulated by the impulse blocker tetrodotoxin (TTX), indicating that their expression was activity-dependent. Silencing of Sp4 blocked the up-regulation of these genes induced by KCl, whereas over-expression of Sp4 rescued them from TTX-induced suppression. The effect of silencing or over-expressing Sp4 on primary neurons was much greater than those of Sp1 or Sp3. The binding sites of Sp factors on these genes are conserved among mice, rats and humans. Thus, Sp4 plays an important role in the transcriptional coupling of energy generation and energy consumption in neurons.