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PLoS One. 2016 Aug 31;11(8):e0161655. doi: 10.1371/journal.pone.0161655. eCollection 2016.

Molecular and Cellular Mechanisms for Trapping and Activating Emotional Memories.

Author information

1
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.
2
Department of Bioengineering, Psychiatry and Behavioral Sciences, Neurosciences Program, CNC Program, Howard Hughes Medical Institute, Stanford University, Stanford, California, United States of America.

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.

PMID:
27579481
PMCID:
PMC5007047
DOI:
10.1371/journal.pone.0161655
[Indexed for MEDLINE]
Free PMC Article

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