The transcription factor calcium-response factor limits NMDA receptor-dependent transcription in the developing brain

Journal of Neurochemistry
Michelle R LyonsA E West

Abstract

Neuronal activity sculpts brain development by inducing the transcription of genes such as brain-derived neurotrophic factor (Bdnf) that modulate the function of synapses. Sensory experience is transduced into changes in gene transcription via the activation of calcium signaling pathways downstream of both L-type voltage-gated calcium channels (L-VGCCs) and NMDA-type glutamate receptors (NMDARs). These signaling pathways converge on the regulation of transcription factors including calcium-response factor (CaRF). Although CaRF is dispensable for the transcriptional induction of Bdnf following the activation of L-VGCCs, here we show that the loss of CaRF leads to enhanced NMDAR-dependent transcription of Bdnf as well as Arc. We identify the NMDAR subunit-encoding gene Grin3a as a regulatory target of CaRF, and we show that expression of both Carf and Grin3a is depressed by the elevation of intracellular calcium, linking the function of this transcriptional regulatory pathway to neuronal activity. We find that light-dependent activation of Bdnf and Arc transcription is enhanced in the visual cortex of young CaRF knockout mice, suggesting a role for CaRF-dependent dampening of NMDAR-dependent transcription in the developing brain....Continue Reading

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Citations

May 7, 2020·Journal of Pediatric Psychology·Bethany G KuertenEve S Puffer
Apr 3, 2020·Cellular and Molecular Neurobiology·Marco ZattoniGiuseppe Legname
Nov 27, 2016·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Joshua L Plotkin, Chengbiao Wu
Dec 9, 2020·Cerebral Cortex·Alvaro MurilloIsabel Pérez-Otaño
Apr 1, 2021·Progress in Neuro-psychopharmacology & Biological Psychiatry·M ObolenskayaT Borisova
May 5, 2021·The Journal of Physiology·Oliver CrawleyIsabel Pérez-Otaño

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