Single genomic enhancers drive experience-dependent GABAergic plasticity to maintain sensory processing in the adult cortex

Abstract

Experience-dependent plasticity of synapses modulates information processing in neural circuits and is essential for cognitive functions. The genome, via non-coding enhancers, was proposed to control information processing and circuit plasticity by regulating experience-induced transcription of genes that modulate specific sets of synapses. To test this idea, we analyze here the cellular and circuit functions of the genomic mechanisms that control the experience-induced transcription of Igf1 (insulin-like growth factor 1) in vasoactive intestinal peptide (VIP) interneurons (INs) in the visual cortex of adult mice. We find that two sensory-induced enhancers selectively and cooperatively drive the activity-induced transcription of Igf1 to thereby promote GABAergic inputs onto VIP INs and to homeostatically control the ratio between excitation and inhibition (E/I ratio)-in turn, this restricts neural activity in VIP INs and principal excitatory neurons and maintains spatial frequency tuning. Thus, enhancer-mediated activity-induced transcription maintains sensory processing in the adult cortex via homeostatic modulation of E/I ratio.

Keywords: E/I ratio; Igf1; VIP interneurons; experience-induced transcription; genomic enhancers; inhibition; synaptic plasticity; visual cortex; visual processing.