Endogenous Acetylcholine and Its Modulation of Cortical Microcircuits to Enhance Cognition
Acetylcholine regulates the cerebral cortex to sharpen sensory perception and enhance attentional focus. The cellular and circuit mechanisms of this cholinergic modulation are under active investigation in sensory and prefrontal cortex, but the universali
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Contents 1 Introduction 2 Anatomy of the Cholinergic System in Prefrontal and Sensory Cortices 2.1 Cholinergic Innervation of Cerebral Cortex 2.2 Cortical Cholinergic Synapses 3 Regulation of Cortical Neurons by Endogenous Acetylcholine 4 Behavioral Consequences of Endogenous Acetylcholine Release in Cerebral Cortex 5 Conclusions and Directions for Future Research References
Abstract Acetylcholine regulates the cerebral cortex to sharpen sensory perception and enhance attentional focus. The cellular and circuit mechanisms of this cholinergic modulation are under active investigation in sensory and prefrontal cortex, but the universality of these mechanisms across the cerebral cortex is not clear. Anatomical maps suggest that the sensory and prefrontal cortices receive distinct cholinergic projections and have subtle differences in the expression of cholinergic receptors and the metabolic enzyme acetylcholinesterase. First, we briefly review this anatomical literature and the recent progress in the field. Next, we discuss in detail the electrophysiological effects of cholinergic receptor subtypes and the cell and circuit consequences of their stimulation by endogenous acetylcholine as established by recent optogenetic work. Finally, we explore the behavioral ramifications of in vivo manipulations of endogenous acetylcholine. We find broader similarities than we
Sridevi Venkatesan and Ha-Seul Jeoung contributed equally to this work. S. Venkatesan, H.-S. Jeoung, T. Chen, S. K. Power, and Y. Liu Department of Physiology, University of Toronto, Toronto, ON, Canada E. K. Lambe (*) Department of Physiology, University of Toronto, Toronto, ON, Canada Department of Obstetrics and Gynaecology, University of Toronto, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada e-mail: [email protected] © Springer Nature Switzerland AG 2020 Curr Topics Behav Neurosci https://doi.org/10.1007/7854_2020_138
S. Venkatesan et al.
expected between the cholinergic regulation of sensory and prefrontal cortex, but there are some differences and some gaps in knowledge. In visual, auditory, and somatosensory cortex, the cell and circuit mechanisms of cholinergic sharpening of sensory perception have been probed in vivo with calcium imaging and optogenetic experiments to simultaneously test mechanism and measure the consequences of manipulation. By contrast, ascertaining the links between attentional performance and cholinergic modulation of specific prefrontal microcircuits is more complicated due to the nature of the required tasks. However, ex vivo optogenetic manipulations point to differences in the cholinergic modulation of sensory and prefrontal cortex. Understanding how and where acetylcholine acts within the cerebral cortex to shape cognition is essential to pinpoint novel treatment targets for the perceptual and attention deficits found in multiple psychiatric and neurological disorders. Keywords Acetylcholine · Attention · Muscarinic receptors · Nicotinic receptors · Prefrontal cortex · Sensory
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