title: Neuronal Allocation to a Hippocampal Engram.
abstract: The dentate gyrus (DG) is important for encoding contextual memories, but little is known about how a population of DG neurons comes to encode and support a particular memory. One possibility is that recruitment into an engram depends on a neuron's excitability. Here, we manipulated excitability by overexpressing CREB in a random population of DG neurons and examined whether this biased their recruitment to an engram supporting a contextual fear memory. To directly assess whether neurons overexpressing CREB at the time of training became critical components of the engram, we examined memory expression while the activity of these neurons was silenced. Chemogenetically (hM4Di, an inhibitory DREADD receptor) or optogenetically (iC++, a light-activated chloride channel) silencing the small number of CREB-overexpressing DG neurons attenuated memory expression, whereas silencing a similar number of random neurons not overexpressing CREB at the time of training did not. As post-encoding reactivation of the activity patterns present during initial experience is thought to be important in memory consolidation, we investigated whether post-training silencing of neurons allocated to an engram disrupted subsequent memory expression. We found that silencing neurons 5 min (but not 24 h) following training disrupted memory expression. Together these results indicate that the rules of neuronal allocation to an engram originally described in the lateral amygdala are followed in different brain regions including DG, and moreover, that disrupting the post-training activity pattern of these neurons prevents memory consolidation.
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Sungmo
authors.initials: S
authors.lastname: Park
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada.|Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
authors.forename: Emily E
authors.initials: EE
authors.lastname: Kramer
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada.|Department of Physiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Valentina
authors.initials: V
authors.lastname: Mercaldo
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada.|Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.|Department of Physiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Asim J
authors.initials: AJ
authors.lastname: Rashid
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada.|Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.|Department of Physiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Nathan
authors.initials: N
authors.lastname: Insel
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada.|Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.|Department of Physiology, University of Toronto, Toronto, ON, Canada.|Department of Psychology, University of Toronto, Toronto, ON, Canada.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Frankland
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON, Canada.|Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.|Department of Physiology, University of Toronto, Toronto, ON, Canada.|Department of Psychology, University of Toronto, Toronto, ON, Canada.
authors.forename: Sheena A
authors.identifier: 0000-0001-5451-489X
authors.initials: SA
authors.lastname: Josselyn
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D003024:Clozapine / Q000031:analogs & derivatives / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D005239:Fear; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D062308:Optogenetics; D014161:Transduction, Genetic
chemical_list: D049452:Green Fluorescent Proteins; D050882:CREB-Binding Protein; D003024:Clozapine; C079149:clozapine N-oxide