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Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):E5584-92. doi: 10.1073/pnas.1421304111. Epub 2014 Dec 8.

Hebbian and neuromodulatory mechanisms interact to trigger associative memory formation.

Author information

1
Laboratory for Neural Circuitry of Memory, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan; Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-0198, Japan; Center for Neural Science, New York University, New York, NY 10003; ledoux@cns.nyu.edu jjohans@brain.riken.jp.
2
Center for Neural Science, New York University, New York, NY 10003;
3
Laboratory for Neural Circuitry of Memory, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan;
4
Department of Bioengineering, Department of Psychiatry and Behavioral Sciences, and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305;
5
McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139; and.
6
Center for Neural Science, New York University, New York, NY 10003; The Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962 ledoux@cns.nyu.edu jjohans@brain.riken.jp.

Abstract

A long-standing hypothesis termed "Hebbian plasticity" suggests that memories are formed through strengthening of synaptic connections between neurons with correlated activity. In contrast, other theories propose that coactivation of Hebbian and neuromodulatory processes produce the synaptic strengthening that underlies memory formation. Using optogenetics we directly tested whether Hebbian plasticity alone is both necessary and sufficient to produce physiological changes mediating actual memory formation in behaving animals. Our previous work with this method suggested that Hebbian mechanisms are sufficient to produce aversive associative learning under artificial conditions involving strong, iterative training. Here we systematically tested whether Hebbian mechanisms are necessary and sufficient to produce associative learning under more moderate training conditions that are similar to those that occur in daily life. We measured neural plasticity in the lateral amygdala, a brain region important for associative memory storage about danger. Our findings provide evidence that Hebbian mechanisms are necessary to produce neural plasticity in the lateral amygdala and behavioral memory formation. However, under these conditions Hebbian mechanisms alone were not sufficient to produce these physiological and behavioral effects unless neuromodulatory systems were coactivated. These results provide insight into how aversive experiences trigger memories and suggest that combined Hebbian and neuromodulatory processes interact to engage associative aversive learning.

KEYWORDS:

Hebbian plasticity; amygdala; associative learning; instructive signals; neuromodulation

PMID:
25489081
PMCID:
PMC4280619
DOI:
10.1073/pnas.1421304111
[Indexed for MEDLINE]
Free PMC Article

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