title: Fast modulation of visual perception by basal forebrain cholinergic neurons.
abstract: The basal forebrain provides the primary source of cholinergic input to the cortex, and it has a crucial function in promoting wakefulness and arousal. However, whether rapid changes in basal forebrain neuron spiking in awake animals can dynamically influence sensory perception is unclear. Here we show that basal forebrain cholinergic neurons rapidly regulate cortical activity and visual perception in awake, behaving mice. Optogenetic activation of the cholinergic neurons or their V1 axon terminals improved performance of a visual discrimination task on a trial-by-trial basis. In V1, basal forebrain activation enhanced visual responses and desynchronized neuronal spiking; these changes could partly account for the behavioral improvement. Conversely, optogenetic basal forebrain inactivation decreased behavioral performance, synchronized cortical activity and impaired visual responses, indicating the importance of cholinergic activity in normal visual processing. These results underscore the causal role of basal forebrain cholinergic neurons in fast, bidirectional modulation of cortical processing and sensory perception.
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720.
authors.forename: Lucas
authors.initials: L
authors.lastname: Pinto
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Goard
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720.
authors.forename: Daniel
authors.initials: D
authors.lastname: Estandian
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720.
authors.forename: Alex C
authors.initials: AC
authors.lastname: Kwan
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720.
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Harrison
authors.affiliation: McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Guoping
authors.initials: G
authors.lastname: Feng
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, CA 94720.
authors.forename: Yang
authors.initials: Y
authors.lastname: Dan
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D019843:Archaeal Proteins / Q000378:metabolism; D000075402:Channelrhodopsins; D002772:Cholera Toxin / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000235:genetics; D059329:Cholinergic Neurons / Q000502:physiology*; D005080:Exercise Test; D005968:Glutamate Decarboxylase / Q000235:genetics; D025602:Halorhodopsins / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000502:physiology; D010775:Photic Stimulation; D016548:Prosencephalon / Q000166:cytology*; D022661:RNA, Untranslated / Q000235:genetics; D014796:Visual Perception / Q000502:physiology*; D017494:Proton Pumps
chemical_list: D000109:Acetylcholine; D019843:Archaeal Proteins; D000075402:Channelrhodopsins; D002772:Cholera Toxin; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D025602:Halorhodopsins; D008164:Luminescent Proteins; D022661:RNA, Untranslated; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; C055476:archaerhodopsin protein, Archaea; D017494:Proton Pumps; C401141:glutamate decarboxylase 2