Basal forebrain cholinergic activity is necessary for upward firing rate homeostasis in the rodent visual cortex

• 成果类型: Article
• 署名作者: Bottorff, Juliet; Padgett, Sydney; Turrigiano, Gina G.
• 署名单位: Brandeis University; Brandeis University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8907
• DOI: 10.1073/pnas.2317987121
• 发表日期: 2024-01-02
• 关键词: pyramidal neuron excitability; nucleus basalis; plasticity; sleep; acetylcholine; modulation; mechanisms; deprivation; wakefulness; receptor

摘要

Bidirectional homeostatic plasticity allows neurons and circuits to maintain stable firing in the face of developmental or learning- induced perturbations. In the primary visual cortex (V1), upward firing rate homeostasis (FRH) only occurs during active wake (AW) and downward during sleep, but how this behavioral state- dependent gating is accomplished is unknown. Here, we focus on how AW enables upward FRH in V1 of juvenile Long Evans rats. A major difference between quiet wake (QW), when upward FRH is absent, and AW, when it is present, is increased cholinergic (ACh) tone, and the main cholinergic projections to V1 arise from the horizontal diagonal band of the basal forebrain (HDB ACh). We therefore chemogenetically inhibited HDB ACh neurons while inducing upward homeostatic compensation using direct activity- suppression in V1. We found that synaptic scaling up and intrinsic homeostatic plasticity, two important cellular mediators of upward FRH, were both impaired when HDB ACh neurons were inhibited. Most strikingly, HDB ACh inhi-bition flipped the sign of intrinsic plasticity so that it became anti- homeostatic, and this effect was phenocopied by knockdown of the M1 ACh receptor in V1, indicat-ing that this modulation of intrinsic plasticity is the result of direct actions of ACh within V1. Finally, we found that upward FRH induced by visual deprivation was completely prevented by HDB ACh inhibition. Together, our results show that HDB ACh modulation is a key enabler of upward homeostatic plasticity and FRH, and more broadly suggest that neuromodulatory inputs can segregate upward and downward homeostatic plasticity into distinct behavioral states. Significance Sleep and wake states influence learning and behavior by modulating many forms of experience- dependent plasticity, including homeostatic mechanisms that stabilize circuit function; how this occurs at the cellular level is poorly understood. Upward homeostasis of neuronal activity during sensory deprivation in visual cortex is confined to active waking states; here, we show that wake- active cholinergic inputs are essential for this homeostatic recovery. Inhibiting these inputs impairs two major cellular forms of upward homeostatic plasticity (synaptic scaling and intrinsic homeostatic plasticity), in part through direct activation of local muscarinic acetylcholine receptors, and prevents activity in visual cortex from undergoing homeostatic recovery. This suggests neuromodulatory inputs during specific vigilance states can orchestrate plasticity within neocortical circuits to promote homeostatic recovery of activity.