Neuronal development shapes activity-dependent gene expression profiles in a stimulus-specific manner

Neuronal activity-dependent gene expression is fundamental to a wide variety of brain functions. Transcriptional profile after in vitro stimulation has been assessed using different modalities to induce neuronal activity. In this work, we first investigate the influence of development on neuronal activity and activity-driven transcription. We used an RNA sequencing approach over 7 days in vitro (DIV) or mature 21 DIV neurons after neuronal depolarization with potassium chloride (KCl)compared to Biccuculine application, a synaptic modality to induce neuronal activity. To further investigate how different activity patterns influence gene transcription in mature neurons, we performed a comparative analysis of global gene expression in neurons treated with extensively used activation protocols KCl, Bic, and TTX withdrawal. Our results demonstrate that different patterns of neuronal activity not only induce different transcriptional profiles but also exhibit distinct temporal dynamics for the same genes. These findings offer novel insights into the complex relationship between neuronal activity and gene expression, shedding light on the context-dependent nature of activity-dependent transcriptional responses. Overall design: We experimentally assessed developmental effects of activity-dependent gene expression programs using mice forebrain primary neuronal cultures. Neurons were cultured for 7 or 21 days and their activity-dependent gene expression profiles upon KCl and Bicuculine stimulation were compared by performing bulk transcriptomic analysis. Additionally, we then compare the effect of KCl, Bicuculline and TTX withdrawal on DIV21 neurons using the same approach