title: Manipulating a "cocaine engram" in mice.
abstract: Experience with drugs of abuse (such as cocaine) produces powerful, long-lasting memories that may be important in the development and persistence of drug addiction. The neural mechanisms that mediate how and where these cocaine memories are encoded, consolidated and stored are unknown. Here we used conditioned place preference in mice to examine the precise neural circuits that support the memory of a cocaine-cue association (the "cocaine memory trace" or "cocaine engram"). We found that a small population of neurons (∼10%) in the lateral nucleus of amygdala (LA) were recruited at the time of cocaine-conditioning to become part of this cocaine engram. Neurons with increased levels of the transcription factor CREB were preferentially recruited or allocated to the cocaine engram. Ablating or silencing neurons overexpressing CREB (but not a similar number of random LA neurons) before testing disrupted the expression of a previously acquired cocaine memory, suggesting that neurons overexpressing CREB become a critical hub in what is likely a larger cocaine memory engram. Consistent with theories that coordinated postencoding reactivation of neurons within an engram or cell assembly is crucial for memory consolidation (Marr, 1971; Buzsáki, 1989; Wilson and McNaughton, 1994; McClelland et al., 1995; Girardeau et al., 2009; Dupret et al., 2010; Carr et al., 2011), we also found that post-training suppression, or nondiscriminate activation, of CREB overexpressing neurons impaired consolidation of the cocaine memory. These findings reveal mechanisms underlying how and where drug memories are encoded and stored in the brain and may also inform the development of treatments for drug addiction.
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada, Institute of Medical Sciences, and Department of Psychology, Physiology, University of Toronto, Toronto, ON, M5G 1X8, Canada, and.
authors.forename: Hwa-Lin Liz
authors.initials: HL
authors.lastname: Hsiang
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada, Institute of Medical Sciences, and Department of Psychology, Physiology, University of Toronto, Toronto, ON, M5G 1X8, Canada, and.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Epp
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada, Institute of Medical Sciences, and Department of Psychology, Physiology, University of Toronto, Toronto, ON, M5G 1X8, Canada, and.
authors.forename: Michel C
authors.initials: MC
authors.lastname: van den Oever
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada, Institute of Medical Sciences, and Department of Psychology, Physiology, University of Toronto, Toronto, ON, M5G 1X8, Canada, and.
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada, Institute of Medical Sciences, and Department of Psychology, Physiology, University of Toronto, Toronto, ON, M5G 1X8, Canada, and.
authors.forename: Asim J
authors.initials: AJ
authors.lastname: Rashid
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada, Institute of Medical Sciences, and Department of Psychology, Physiology, University of Toronto, Toronto, ON, M5G 1X8, Canada, and.
authors.forename: Nathan
authors.initials: N
authors.lastname: Insel
authors.affiliation: Department of Bioengineering and Psychiatry, Stanford University, Stanford, California 94305.
authors.forename: Li
authors.initials: L
authors.lastname: Ye
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada, Institute of Medical Sciences, and Department of Psychology, Physiology, University of Toronto, Toronto, ON, M5G 1X8, Canada, and.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Niibori
authors.affiliation: Department of Bioengineering and Psychiatry, Stanford University, Stanford, California 94305.
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada, Institute of Medical Sciences, and Department of Psychology, Physiology, University of Toronto, Toronto, ON, M5G 1X8, Canada, and.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Frankland
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada, Institute of Medical Sciences, and Department of Psychology, Physiology, University of Toronto, Toronto, ON, M5G 1X8, Canada, and sheena.josselyn@sickkids.ca.
authors.forename: Sheena A
authors.initials: SA
authors.lastname: Josselyn
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis*; D005260:Female; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D003042:Cocaine
keywords: amygdala; cocaine; conditioning; memory; place preference