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

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.

NDNF interneurons in layer 1 gain-modulate whole cortical columns according to an animal's behavioral state.

Processing of sensory information in neural circuits is modulated by an animal's behavioral state, but the underlying cellular mechanisms are not well understood. Focusing on the mouse visual cortex, here we analyze the role of GABAergic interneurons that are located in layer 1 and express Ndnf (L1 NDNF INs) in the state-dependent control over sensory processing. We find that the ongoing and sensory-evoked activity of L1 NDNF INs is strongly enhanced when an animal is aroused and that L1 NDNF INs gain-modulate local excitatory neurons selectively during high-arousal states by inhibiting their apical dendrites while disinhibiting their somata via Parvalbumin-expressing interneurons. Because active NDNF INs are evenly spread in L1 and can affect excitatory neurons across all cortical layers, this indicates that the state-dependent activation of L1 NDNF INs and the subsequent shift of inhibition in excitatory neurons toward their apical dendrites gain-modulate sensory processing in whole cortical columns.