title: Wiring and Molecular Features of Prefrontal Ensembles Representing Distinct Experiences.
abstract: A major challenge in understanding the cellular diversity of the brain has been linking activity during behavior with standard cellular typology. For example, it has not been possible to determine whether principal neurons in prefrontal cortex active during distinct experiences represent separable cell types, and it is not known whether these differentially active cells exert distinct causal influences on behavior. Here, we develop quantitative hydrogel-based technologies to connect activity in cells reporting on behavioral experience with measures for both brain-wide wiring and molecular phenotype. We find that positive and negative-valence experiences in prefrontal cortex are represented by cell populations that differ in their causal impact on behavior, long-range wiring, and gene expression profiles, with the major discriminant being expression of the adaptation-linked gene NPAS4. These findings illuminate cellular logic of prefrontal cortex information processing and natural adaptive behavior and may point the way to cell-type-specific understanding and treatment of disease-associated states.
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Neurosciences Program, Stanford University, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Allen
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Thompson
authors.affiliation: Department of Radiology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Qiyuan
authors.initials: Q
authors.lastname: Tian
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA; Neurosciences Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Hsueh
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Charu
authors.initials: C
authors.lastname: Ramakrishnan
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Ai-Chi
authors.initials: AC
authors.lastname: Wang
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Joshua H
authors.initials: JH
authors.lastname: Jennings
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA.
authors.forename: Avishek
authors.initials: A
authors.lastname: Adhikari
authors.affiliation: Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA.
authors.forename: Casey H
authors.initials: CH
authors.lastname: Halpern
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Ilana B
authors.initials: IB
authors.lastname: Witten
authors.affiliation: Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
authors.forename: Alison L
authors.initials: AL
authors.lastname: Barth
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Radiology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: McNab
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA; Department of Psychiatry, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. Electronic address: deissero@stanford.edu.
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
mesh_terms: D000818:Animals; D001070:Appetitive Behavior; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001522:Behavior, Animal; D001931:Brain Mapping / Q000379:methods*; D003042:Cocaine / Q000008:administration & dosage; D004597:Electroshock; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017397:Prefrontal Cortex / Q000166:cytology* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D003042:Cocaine; C533005:Npas4 protein, mouse