COMMONLY USED NEURONAL-ACTIVATION PROTOCOLS INDUCE DISTINCT mRNA EXPRESSION PROFILES

PATOP, INES; GIUSTI, SEBASTIAN; REFOJO, DAMIÁN; LUKIN, JERONIMO; NGUYEN, SINEAD; KADENER, SEBASTIAN; PEDRONCINI, OLIVIA; OGANDO, MORA; MARIN-BURGIN, ANTONIA

Nassau

Congreso; 2nd Neuroepigenetics & Neuroepitranscriptomics Conference; 2020

Fusion Conferences

In neuronal networks, activity-dependent gene expression is necessary to implement the synaptic plasticity mechanisms required to encode, store and retrieve long-lasting information. However, the precise activity- transcription coupling mechanisms are not fully understood.Several studies have approached this question using a restricted set of stimulation protocols: KCl, Bicuculline/4-AP and TTX withdrawal among others. These treatments strongly induce activity-regulated genes and were crucial for our current understanding of the basic principles guiding activity-transcription coupling. However, as these compounds have different mechanisms of action, we wonder whether they can be truly considered as equivalent protocols to assess activity-induced gene expression.To address this question, we performed a transcriptomic analysis to compare the mRNA profiles triggered by these commonly used activation approaches. We stimulated neuronal cultures with KCl, Bicuculline/4-AP and TTX withdrawal and analyzed their mRNA expression levels at different time-points. We found that each stimulation protocol triggers specific modules of immediate-early genes with particular temporal dynamics and secondary waves of transcription. These results indicate that classical stimulation protocols are not functionally equivalent in terms of activity-regulated genes. This probably reflects the different molecular events used by each activation protocol which in turn trigger distinct downstream signals towards the nucleus with specific spatio-temporal dynamics.