title: CREB regulates spine density of lateral amygdala neurons: implications for memory allocation.
abstract: Neurons may compete against one another for integration into a memory trace. Specifically, neurons in the lateral nucleus of the amygdala with relatively higher levels of cAMP Responsive Element Binding Protein (CREB) seem to be preferentially allocated to a fear memory trace, while neurons with relatively decreased CREB function seem to be excluded from a fear memory trace. CREB is a ubiquitous transcription factor that modulates many diverse cellular processes, raising the question as to which of these CREB-mediated processes underlie memory allocation. CREB is implicated in modulating dendritic spine number and morphology. As dendritic spines are intimately involved in memory formation, we investigated whether manipulations of CREB function alter spine number or morphology of neurons at the time of fear conditioning. We used viral vectors to manipulate CREB function in the lateral amygdala (LA) principal neurons in mice maintained in their homecages. At the time that fear conditioning normally occurs, we observed that neurons with high levels of CREB had more dendritic spines, while neurons with low CREB function had relatively fewer spines compared to control neurons. These results suggest that the modulation of spine density provides a potential mechanism for preferential allocation of a subset of neurons to the memory trace.
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children Toronto, ON, Canada ; Department of Psychology, University of Toronto Toronto, ON, Canada ; Department of Physiology, University of Toronto Toronto, ON, Canada ; Institute of Medical Science, University of Toronto Toronto, ON, Canada.
authors.forename: Derya
authors.initials: D
authors.lastname: Sargin
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children Toronto, ON, Canada ; Department of Psychology, University of Toronto Toronto, ON, Canada ; Department of Physiology, University of Toronto Toronto, ON, Canada ; Institute of Medical Science, 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 ; Department of Psychology, University of Toronto Toronto, ON, Canada ; Department of Physiology, University of Toronto Toronto, ON, Canada ; Institute of Medical Science, University of Toronto Toronto, ON, Canada.
authors.forename: Adelaide P
authors.initials: AP
authors.lastname: Yiu
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children Toronto, ON, Canada ; Department of Psychology, University of Toronto Toronto, ON, Canada ; Department of Physiology, University of Toronto Toronto, ON, Canada ; Institute of Medical Science, University of Toronto Toronto, ON, Canada.
authors.forename: Gemma
authors.initials: G
authors.lastname: Higgs
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children Toronto, ON, Canada ; Department of Psychology, University of Toronto Toronto, ON, Canada ; Department of Physiology, University of Toronto Toronto, ON, Canada ; Institute of Medical Science, University of Toronto Toronto, ON, Canada ; Laboratory of Neural Circuit and Behavior, Department of Biological Sciences, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology Daejeon, Korea.
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Han
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children Toronto, ON, Canada ; Department of Psychology, University of Toronto Toronto, ON, Canada ; Department of Physiology, University of Toronto Toronto, ON, Canada ; Institute of Medical Science, 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 ; Department of Psychology, University of Toronto Toronto, ON, Canada ; Department of Physiology, University of Toronto Toronto, ON, Canada ; Institute of Medical Science, University of Toronto Toronto, ON, Canada.
authors.forename: Sheena A
authors.initials: SA
authors.lastname: Josselyn
keywords: CREB; amygdala; dendritic spines; fear memory; viral vector