title: Selective activation of a putative reinforcement signal conditions cued interval timing in primary visual cortex.
abstract: As a consequence of conditioning visual cues with delayed reward, cue-evoked neural activity that predicts the time of expected future reward emerges in the primary visual cortex (V1). We hypothesized that this reward-timing activity is engendered by a reinforcement signal conveying reward acquisition to V1. In lieu of behavioral conditioning, we assessed in vivo whether selective activation of either basal forebrain (BF) or cholinergic innervation is sufficient to condition cued interval-timing activity. Substituting for actual reward, optogenetic activation of BF or cholinergic input within V1 at fixed delays following visual stimulation entrains neural responses that mimic behaviorally conditioned reward-timing activity. Optogenetically conditioned neural responses express cue-evoked temporal intervals that correspond to the conditioning intervals, are bidirectionally modifiable, display experience-dependent refinement, and exhibit a scale invariance to the encoded delay. Our results demonstrate that the activation of BF or cholinergic input within V1 is sufficient to encode cued interval-timing activity and indicate that V1 itself is a substrate for associative learning that may inform the timing of visually cued behaviors.
authors.affiliation: Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Cheng-Hang
authors.initials: CH
authors.lastname: Liu
authors.affiliation: The Picower Institute for Learning and Memory, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Child Health Research Institute, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610, USA.
authors.forename: Jason E
authors.initials: JE
authors.lastname: Coleman
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Heydar
authors.initials: H
authors.lastname: Davoudi
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Kechen
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: shuler@jhmi.edu.
authors.forename: Marshall G
authors.initials: MG
authors.lastname: Hussain Shuler
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003463:Cues; D005071:Evoked Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D010775:Photic Stimulation; D012201:Reward; D014793:Visual Cortex / Q000502:physiology*