IEGs

Immediate early genes (IEGs) are a class of genes rapidly activated in response to cellular stimuli, particularly neuronal activity. IEG transcription occurs within minutes of stimulation and often does not require new protein synthesis, positioning them upstream in gene regulatory cascades. The encoded proteins include transcription factors and regulators that help initiate longer-term gene expression programs.

Common neuronal IEGs include c-Fos, Arc (Arg3.1), Egr1 (also known as zif268), FosB, and Npas4. Arc is notable for its role in synaptic plasticity and AMPA receptor trafficking; c-Fos and Egr1 function as transcription factors that regulate downstream gene networks; Npas4 selectively controls formation of inhibitory synapses in response to activity.

Activation mechanisms: neuronal activity elevates intracellular Ca2+ via NMDA receptors and voltage-gated calcium channels, triggering signaling cascades (MAPK/ERK, CaMK pathways) that activate CREB and other transcription factors.

Uses and caveats: IEG expression is used as a proxy for neuronal activity to map active circuits during behavior, with techniques like immunohistochemistry or in situ hybridization. However, IEG induction is not entirely specific to a particular stimulus; stress, anesthesia, or systemic factors can alter expression. Temporal resolution is limited to minutes for induction and hours to return to baseline, so careful experimental design is required.

Beyond neurons, IEGs are studied in other cell types and contexts; in neuroscience, they provide insights into mechanisms of learning, memory consolidation, and experience-dependent plasticity.