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Cholinergic inputs from the basal forebrain to the neocortex and hippocampus have a key role in mechanisms of arousal, attention, sensory processing, and memory. Acetylcholine (ACh) exerts multiple effects in the cerebral cortex via muscarinic (mAChR) and nicotinic (nAChR) receptors located presynaptically and postsynaptically in both pyramidal glutamatergic projection and local γ-aminobutyric acid (GABA)-ergic neurons. Through its multiple actions, ACh affects signal-to-noise ratio during sensory processing and modulates synchronization of neuronal networks. The physiologic effects of ACh include enhancement of both attention to sensory stimuli and encoding of memory for specific stimuli. Experimental studies using a variety of approaches have provided insight into the mechanisms of cholinergic modulation of cortical function and cognition. The basal forebrain cholinergic system is affected in several neurodegenerative disorders, including Alzheimer disease (AD), Parkinson disease (PD), and dementia with Lewy bodies (DLB), and may contribute to behavioral manifestations of psychiatric disorders such as schizophrenia. Functional neuroimaging allows the exploration of the effects of cholinergic cortical modulation in healthy subjects and its alterations in patients with neurodegenerative disorders. The recognition of the importance of ACh in normal cortical function has stimulated major advances in the discovery of novel pharmacologic approaches to these conditions. Many of these subjects have been comprehensively covered in excellent reviews.1–12
ANATOMY, PHYSIOLOGY, AND NEUROCHEMISTRY OF CHOLINERGIC INPUTS TO THE CEREBRAL CORTEX
Main connections.
Neurons of the basal forebrain are the major source of ACh supplying the neocortex and hippocampus (figure 1). They include the Ch1–Ch3 subgroups located in the medial septum and diagonal band of Broca, providing innervation of the hippocampus, and the Ch4 subgroup located in the nucleus basalis magnocellularis (NBM) and innervating the cerebral cortex and amygdala.1 Survival of basal forebrain cholinergic neurons depends on the trophic effects nerve growth factor, which is synthesized and secreted by cells in the cortex and hippocampus, binds to tyrosine kinase A receptors, and travels …
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