title: Hebbian and neuromodulatory mechanisms interact to trigger associative memory formation.
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.
authors.affiliation: 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.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Johansen
authors.affiliation: Center for Neural Science, New York University, New York, NY 10003;
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Diaz-Mataix
authors.affiliation: Laboratory for Neural Circuitry of Memory, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan;
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hamanaka
authors.affiliation: Laboratory for Neural Circuitry of Memory, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan;
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ozawa
authors.affiliation: Laboratory for Neural Circuitry of Memory, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan;
authors.forename: Edgar
authors.initials: E
authors.lastname: Ycu
authors.affiliation: Laboratory for Neural Circuitry of Memory, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan;
authors.forename: Jenny
authors.initials: J
authors.lastname: Koivumaa
authors.affiliation: Laboratory for Neural Circuitry of Memory, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan;
authors.forename: Ashwani
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Center for Neural Science, New York University, New York, NY 10003;
authors.forename: Mian
authors.initials: M
authors.lastname: Hou
authors.affiliation: Department of Bioengineering, Department of Psychiatry and Behavioral Sciences, and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305;
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.affiliation: McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139; and.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Boyden
authors.affiliation: 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.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: LeDoux
mesh_terms: D000679:Amygdala / Q000166:cytology / Q000502:physiology; D000818:Animals; D001245:Association Learning; D001362:Avoidance Learning; D008297:Male; D008568:Memory; D009473:Neuronal Plasticity; D017966:Pyramidal Cells; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Hebbian plasticity; amygdala; associative learning; instructive signals; neuromodulation