@article{a204cb674b0c4ce487419ebb7f238d10,
title = "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.",
author = "O Roethler and E Zohar and {Cohen Kashi}, Katayun and L Bitan and HW Gabel and I Spiegel",
note = "We thank all the members of the Spiegel lab for comments and discussions, Mr. Hasan Heidar and Ms. Shakked Ganor for assistance with animal husbandry, and Drs. Ofer Yizhar and Igor Ulitsky (Weizmann Institute of Science) for critical reading of the manuscript. We also thank Drs. Shifra Ben-Dor and Rebecca Haffner-Krausz (respectively at the Weizmann Institute life science core units for Bioinformatics and for Transgenic Animals) for their help with generating the Igf1-E2/3 flox and Igf1-E12/3 flox mice and Dr. Tomer Meir Salame (at the Weizmann Institute Flow Cytometry unit) for help with the FACS experiments. We would especially like to thank Dr. Michael E. Greenberg (Harvard Medical School) for his generous support throughout this project and for sharing unpublished findings. This work was supported by an ISF I-CORE grant (1916/12), an ISF personal grant (2354/19), and a BSF US-Israel binational grant (2017342), all for I.S. O.R. is supported by a fellowship from the Israel Ministry of Absorption (IMOAb). I.S. is the incumbent of the Friends and Linda and Richard Price Career Development Chair and a scholar in the Zuckerman STEM leadership program.",
year = "2023",
month = sep,
day = "6",
doi = "10.1016/j.neuron.2023.05.026",
language = "الإنجليزيّة",
volume = "111",
pages = "2693--2708.e8",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "17",
}