The neuronal stimulation-transcription coupling map

Abstract

Neurons transcribe different genes in response to different extracellular stimuli, and these genes regulate neuronal plasticity. Thus, understanding how different stimuli regulate different stimulus-dependent gene modules would deepen our understanding of plasticity. To systematically dissect the coupling between stimulation and transcription, we propose creating a 'stimulation-transcription coupling map' that describes the transcription response to each possible extracellular stimulus. While we are currently far from having a complete map, recent genomic experiments have begun to facilitate its creation. Here, we describe the current state of the stimulation-transcription coupling map as well as the transcriptional regulation that enables this coupling.

Figure 1.. The neuronal stimulation-transcription coupling map.

We propose creating a stimulation-transcription coupling map that would link stimulation space (all possible different stimuli) to transcription space (all possible transcription programs). Here we show an example of three theoretical couplings between stimulation space and transcription space, depicted on a simplified three-dimensional stimulation space defined by the spatial pattern (x) molecular identity (y), and temporal pattern (z) of the stimulus.

Figure 2.. Principles of stimulation-transcription and its transcriptional regulation.

A. Neuronal excitation and inhibition regulate different, partly reciprocal gene programs, with excitation regulating more genes than inhibition. B. Neurons stimulated at higher frequencies transcribe ARGs at higher levels. C. Neurons stimulated for brief durations selectively transcribe a rapid gene module, whereas neurons stimulated for longer durations also transcribe a delayed gene module. D. Stimulation of synaptic NMDA receptors induces transcription of synaptic plasticity and prosurvival genes, whereas stimulation of extrasynaptic NMDA receptors induces transcription of cell-death genes. E. Different sources of depolarization engage different transcription factor complexes.