title: Molecular and Cellular Mechanisms for Trapping and Activating Emotional Memories.
abstract: Recent findings suggest that memory allocation to specific neurons (i.e., neuronal allocation) in the amygdala is not random, but rather the transcription factor cAMP-response element binding protein (CREB) modulates this process, perhaps by regulating the transcription of channels that control neuronal excitability. Here, optogenetic studies in the mouse lateral amygdala (LA) were used to demonstrate that CREB and neuronal excitability regulate which neurons encode an emotional memory. To test the role of CREB in memory allocation, we overexpressed CREB in the lateral amygdala to recruit the encoding of an auditory-fear conditioning (AFC) memory to a subset of neurons. Then, post-training activation of these neurons with Channelrhodopsin-2 was sufficient to trigger recall of the memory for AFC, suggesting that CREB regulates memory allocation. To test the role of neuronal excitability in memory allocation, we used a step function opsin (SFO) to transiently increase neuronal excitability in a subset of LA neurons during AFC. Post-training activation of these neurons with Volvox Channelrhodopsin-1 was able to trigger recall of that memory. Importantly, our studies show that activation of the SFO did not affect AFC by either increasing anxiety or by strengthening the unconditioned stimulus. Our findings strongly support the hypothesis that CREB regulates memory allocation by modulating neuronal excitability.
authors: Integrative Center for Learning and Memory, Departments of Neurobiology, Psychology, and Psychiatry & Biobehavioral Sciences, and Brain Research Institute, Los Angeles, California, United States of America.
authors: Thomas
authors: T
authors: Rogerson
authors: Integrative Center for Learning and Memory, Departments of Neurobiology, Psychology, and Psychiatry & Biobehavioral Sciences, and Brain Research Institute, Los Angeles, California, United States of America.
authors: Balaji
authors: B
authors: Jayaprakash
authors: Integrative Center for Learning and Memory, Departments of Neurobiology, Psychology, and Psychiatry & Biobehavioral Sciences, and Brain Research Institute, Los Angeles, California, United States of America.
authors: Denise J
authors: DJ
authors: Cai
authors: Integrative Center for Learning and Memory, Departments of Neurobiology, Psychology, and Psychiatry & Biobehavioral Sciences, and Brain Research Institute, Los Angeles, California, United States of America.
authors: Yoshitake
authors: Y
authors: Sano
authors: Integrative Center for Learning and Memory, Departments of Neurobiology, Psychology, and Psychiatry & Biobehavioral Sciences, and Brain Research Institute, Los Angeles, California, United States of America.
authors: Yong-Seok
authors: YS
authors: Lee
authors: Integrative Center for Learning and Memory, Departments of Neurobiology, Psychology, and Psychiatry & Biobehavioral Sciences, and Brain Research Institute, Los Angeles, California, United States of America.
authors: Yu
authors: Y
authors: Zhou
authors: Integrative Center for Learning and Memory, Departments of Neurobiology, Psychology, and Psychiatry & Biobehavioral Sciences, and Brain Research Institute, Los Angeles, California, United States of America.
authors: Pallavi
authors: P
authors: Bekal
authors: Department of Bioengineering, Psychiatry and Behavioral Sciences, Neurosciences Program, CNC Program, Howard Hughes Medical Institute, Stanford University, Stanford, California, United States of America.
authors: Karl
authors: K
authors: Deisseroth
authors: Integrative Center for Learning and Memory, Departments of Neurobiology, Psychology, and Psychiatry & Biobehavioral Sciences, and Brain Research Institute, Los Angeles, California, United States of America.
authors: Alcino J
authors: AJ
authors: Silva
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D000075402:Channelrhodopsins; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005239:Fear / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D055355:Opsins / Q000378:metabolism*
chemical_list: D000075402:Channelrhodopsins; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D055355:Opsins