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Authors & Affiliations
Giulia Fois, Maria Carmen Medrano, Stephanie Caillé-Garnier, Karine Guillem
Abstract
Acetylcholine (ACh) release in the medial prefrontal cortex (mPFC) is essential to numerous cognitive functions and disruptions of cortical ACh transmission has been implicated in several disorders, including attentional deficit hyperactivity disorder (ADHD), Alzheimer’s disease or schizophrenia and addictive behavior. Similarly in rodents, it has been shown that cognitive functions rely on the mPFC neuronal activity and that ACh release can modulate mPFC neuronal activity thereby altering cognitive behaviors, in particular attention. The main ACh innervation of mPFC originates in basal forebrain (BF) which includes the nucleus basalis of Meynert (B), the substantia innominata (SI), the diagonal band of Broca (DB) and the preoptic nucleus. Though these BF-mPFC cholinergic projections have been classically viewed as diffuse and thought to produce global and uniform effects in the mPFC, recent anatomical evidence rather suggests a heterogeneous spatial and segregated distribution. Moreover, in rodents, both the attention and inhibitory controls can be studied using the fixed consecutive number (FCN) task which aims to measure the ability of mice to carry out a chain of sequential actions to achieve a goal. Here, we first highlighted the existence of two distinct specific ACh-pathways within the BF that selectively innervate different sub-regions of the mPFC. Then we assessed the role of this specific BF cholinergic inputs to the mPFC on cognitive performances using a multi-level approach combining the FCN task with fiberphotometry and chemogenetic approches for brain activity recording and manipulation.