The Basal Forebrain Cholinergic Projection System in Mice

The basal forebrain is composed of an affiliation of heterogeneous structures and includes the medial septum, ventral pallidum (VP), diagonal band nuclei, substantia innominata/extended amygdala, and peripallidal regions. The basal forebrain is located close to the medial and ventral surfaces of the cerebral hemispheres that develop from the subpallium. This highly complex brain region has been implicated in cortical activation, attention, motivation, memory, and neuropsychiatric disorders such as Alzheimer's disease Parkinson's disease, schizophrenia, and drug abuse. The basal forebrain contains a heterogeneous mixture of cell types that differ in transmitter content, morphology, and projection pattern. One of the most prominent features of the mammalian basal forebrain is the presence of a collection of aggregated and non-aggregated, large, hyperchromic neurons, many of them containing choline acetyl transferase (ChAT), the critical enzyme in the synthesis of acetylcholine (ACh); these neurons project to the cerebral cortex. Single unit studies in anesthetized and behaving rats showed that identified cholinergic neurons increase their firing during cortical EEG activation. Activity of basal forebrain cholinergic neurons is associated with an increase in cortical release of ACh. Cortical ACh release is high during wakefulness and rapid eye movement (REM) sleep and is low during non-REM sleep that is characterized by EEG delta power with periodic oscillations of medium-frequency high amplitude spindles. Against the relatively "diffuse" termination of the ascending brainstem and hypothalamic axons in the basal forebrain, the restricted input from the prefrontal cortex to basal forebrain neurons, including specific clusters, might be instrumental in communicating state-related changes from basal forebrain neurons to specific posterior sensory areas to modulate selective cognitive processes.