Abstract
Immediate early genes (IEGs) are transcribed in response to neuronal activity from sensory stimulation during multiple adaptive processes in the brain. The transcriptional profile of IEGs is indicative of the duration of neuronal activity, but its sensitivity to the strength of depolarization remains unknown. Also unknown is whether activity history of graded potential changes influence future neuronal activity. In this work with dissociated rat cortical neurons, we found that mild depolarization—mediated by elevated extracellular potassium (K+)—induces a wide array of rapid IEGs and transiently depresses transcriptional and signaling responses to a successive stimulus. This latter effect was independent of de novo transcription, translation, and signaling via calcineurin or mitogen-activated protein kinase. Furthermore, as measured by multiple electrode arrays and calcium imaging, mild depolarization acutely subdues subsequent spontaneous and bicuculline-evoked activity via calcium- and N-methyl-D-aspartate receptor–dependent mechanisms. Collectively, this work suggests that a recent history of graded potential changes acutely depress neuronal intrinsic properties and subsequent responses. Such effects may have several potential downstream implications, including reducing signal-to-noise ratio during synaptic plasticity processes.
Original language | English (US) |
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Article number | 102278 |
Journal | Journal of Biological Chemistry |
Volume | 298 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2022 |
Bibliographical note
Funding Information:We thank Karen Cornejo, Andie Venegas, and other Saha laboratory members for their support and constructive criticism during experimentation and article preparation. R. N. S. conceptualization; K. D. A. R. R. G. P. J. S. S. I. W. F. M. H. S. S. J. M. M. G.-E. A. R. S. T.-G. E. M. F. d. V. S. A. T. and R. N. S. investigation; K. D. A. R. R. G. P. I. W. F. S. A. T. and R. N. S. formal analysis; K. D. A. R. R. G. P. and R. N. S. writing–original draft; K. D. A. R. R. G. P. I. W. F. S. A. T. and R. N. S. visualization; R. N. S. supervision; K. W. S. A. T. and R. N. S. funding acquisition. The study was conducted under the auspices of National Institutes of Health grants from the National Institute of Environmental Health Sciences (grant no.: R01ES028738; to R. N. S.) and the National Institute on Drug Abuse (grant nos.: R01DA07304 [to S. A. T.]; R01DA034696, also R01AA027544; to K. W.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
The study was conducted under the auspices of National Institutes of Health grants from the National Institute of Environmental Health Sciences (grant no.: R01ES028738; to R. N. S.) and the National Institute on Drug Abuse (grant nos.: R01DA07304 [to S. A. T.]; R01DA034696, also R01AA027544; to K. W.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2022 The Authors
Keywords
- immediate early genes
- intrinsic excitability
- membrane depolarization
- neuronal activity
- transcription