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J Neurosci. 2015 Oct 14;35(41):13896-903. doi: 10.1523/JNEUROSCI.2590-15.2015.

Optogenetic Dissection of the Basal Forebrain Neuromodulatory Control of Cortical Activation, Plasticity, and Cognition.

Author information

National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224,
Department of Psychiatry, Veterans Administration Boston Healthcare System and Harvard Medical School, Brockton, Massachusetts 02301.
Department of Neuroscience, Johns Hopkins University, Baltimore, Maryland 21205.
Laboratory of Sensory Processing, Brain Mind Institute, Federal Institute of Technology of Lausanne, CH-1015 Lausanne, Switzerland, and.
Neuroscience, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724.


The basal forebrain (BF) houses major ascending projections to the entire neocortex that have long been implicated in arousal, learning, and attention. The disruption of the BF has been linked with major neurological disorders, such as coma and Alzheimer's disease, as well as in normal cognitive aging. Although it is best known for its cholinergic neurons, the BF is in fact an anatomically and neurochemically complex structure. Recent studies using transgenic mouse lines to target specific BF cell types have led to a renaissance in the study of the BF and are beginning to yield new insights about cell-type-specific circuit mechanisms during behavior. These approaches enable us to determine the behavioral conditions under which cholinergic and noncholinergic BF neurons are activated and how they control cortical processing to influence behavior. Here we discuss recent advances that have expanded our knowledge about this poorly understood brain region and laid the foundation for future cell-type-specific manipulations to modulate arousal, attention, and cortical plasticity in neurological disorders.


Although the basal forebrain is best known for, and often equated with, acetylcholine-containing neurons that provide most of the cholinergic innervation of the neocortex, it is in fact an anatomically and neurochemically complex structure. Recent studies using transgenic mouse lines to target specific cell types in the basal forebrain have led to a renaissance in this field and are beginning to dissect circuit mechanisms in the basal forebrain during behavior. This review discusses recent advances in the roles of basal forebrain cholinergic and noncholinergic neurons in cognition via their dynamic modulation of cortical activity.


GABAergic; cortical state; motivational salience; nucleus basalis; reinforcement; reward timing

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