Specific Basal Forebrain-Cortical Cholinergic Circuits Coordinate Cognitive Operations

J Neurosci. 2018 Oct 31;38(44):9446-9458. doi: 10.1523/JNEUROSCI.1676-18.2018.


Based on recent molecular genetics, as well as functional and quantitative anatomical studies, the basal forebrain (BF) cholinergic projections, once viewed as a diffuse system, are emerging as being remarkably specific in connectivity. Acetylcholine (ACh) can rapidly and selectively modulate activity of specific circuits and ACh release can be coordinated in multiple areas that are related to particular aspects of cognitive processing. This review discusses how a combination of multiple new approaches with more established techniques are being used to finally reveal how cholinergic neurons, together with other BF neurons, provide temporal structure for behavior, contribute to local cortical state regulation, and coordinate activity between different functionally related cortical circuits. ACh selectively modulates dynamics for encoding and attention within individual cortical circuits, allows for important transitions during sleep, and shapes the fidelity of sensory processing by changing the correlation structure of neural firing. The importance of this system for integrated and fluid behavioral function is underscored by its disease-modifying role; the demise of BF cholinergic neurons has long been established in Alzheimer's disease and recent studies have revealed the involvement of the cholinergic system in modulation of anxiety-related circuits. Therefore, the BF cholinergic system plays a pivotal role in modulating the dynamics of the brain during sleep and behavior, as foretold by the intricacies of its anatomical map.

Keywords: basal forebrain population dynamics; cholinergic engram of fear; cortico-cortical coherence; dynamics of encoding and retrieval; signal and noise correlation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / metabolism
  • Aging / pathology
  • Aging / psychology
  • Animals
  • Basal Forebrain / metabolism*
  • Basal Forebrain / pathology
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Cholinergic Neurons / metabolism*
  • Cholinergic Neurons / pathology
  • Cognition / physiology*
  • Dementia / diagnosis
  • Dementia / physiopathology
  • Dementia / psychology
  • Humans
  • Nerve Net / metabolism*
  • Nerve Net / pathology