Decoding the regulation of activity-dependent gene expression programs in neurons

JERÓNIMO LUKIN; PEDRONCINI, O; BECKEL, MAXIMILIANO; GIUSTI, SEBASTIÁN A.; CHERNOMORETZ, ARIEL; KADENER, S; ANTONIA MARIN-BURGIN; DAMIAN REFOJO

Congreso; XXXVI REUNIÓN ANUAL SAN; 2021

Sociedad Argentina de Investigación en Neurociencias

Activity-driven gene expression is necessary to implement synaptic plasticity mechanisms required to encode, store and retrieve long-lasting information. How neurons integrate and process neuronal activity patterns and translate them into specific activity-driven gene transcription programs is still not clear.To address this question, we employed different neuronal activation protocols available in the literature that are known to elicit different specific patterns of neuronal responses: KCl depolarization, Bicuculline and Tetrodotoxin withdrawal. Taking advantage of the neuronal activity patterns generated by these mechanisms, we performed cortical neuronal primary cultures and stimulated neurons. Upon these protocols, we extracted RNA and protein samples at different time points and performed RNA libraries and sequencing and western blot analysis.Genome-wide analysis reveals distinct gene expression profiles and dynamics induced upon each neuronal activity pattern and phosphorylation dynamics of Ca2+ dependent proteins as ERK and p38 may explain part of these differences. Additionally, comparing 7DIV vs 21DIV cultures we found that the neuronal maturational stage strongly influences the transcriptional response elicited by neuronal activation. We conclude that a neuron can differentially translate its activity into specific cellular programs that involve distinct gene expression and protein phosphorylation programs.