• Rajan Dasgupta, Frederik Seibt, and Michael Beierlein.
• Department of Neurobiology and Anatomy, McGovern Medical School at UTHealth, Houston, Texas 77030 and.
• J. Neurosci. 2018 Jun 6; 38 (23): 5338-5350.

AbstractCholinergic afferents from the basal forebrain (BF) can influence cortical activity on rapid time scales, enabling sensory information processing and exploratory behavior. However, our understanding of how synaptically released acetylcholine (ACh) influences cellular targets in distinct cortical layers remains incomplete. Previous studies have shown that rapid changes in cortical dynamics induced by phasic BF activity can be mediated by the activation of nicotinic ACh receptors (nAChRs) expressed in distinct types of GABAergic interneurons. In contrast, muscarinic ACh receptors (mAChRs) are assumed to be involved in slower and more diffuse ACh signaling following sustained increases in afferent activity. Here, we examined the mechanisms underlying fast cholinergic control of cortical circuit dynamics by pairing optical stimulation of cholinergic afferents with evoked activity in somatosensory cortical slices of mice of either sex. ACh release evoked by single stimuli led to a rapid and persistent suppression of cortical activity, mediated by mAChRs expressed in layer 4 and to a lesser extent, by nAChRs in layers 1-3. In agreement, we found that cholinergic inputs to layer 4 evoked short-latency and long-lasting mAChR-dependent inhibition of the large majority of excitatory neurons, whereas inputs to layers 1-3 primarily evoked nAChR-dependent excitation of different classes of interneurons. Our results indicate that the rapid cholinergic control of cortical network dynamics is mediated by both nAChRs and mAChRs-dependent mechanisms, which are expressed in distinct cortical layers and cell types.SIGNIFICANCE STATEMENT Acetylcholine (ACh) release from basal forebrain (BF) afferents to cortex influences a variety of cognitive functions including attention, sensory processing, and learning. Cholinergic control occurs on the time scale of seconds and is mediated by BF neurons that generate action potentials at low rates, indicating that ACh acts as a point-to-point neurotransmitter. Our findings highlight that even brief activation of cholinergic afferents can recruit both nicotinic and muscarinic ACh receptors expressed in several cell types, leading to modulation of cortical activity on distinct time scales. Furthermore, they indicate that the initial stages of cortical sensory processing are under direct cholinergic control.Copyright © 2018 the authors 0270-6474/18/385338-13$15.00/0.

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