Hebbian and neuromodulatory mechanisms interact to trigger associative memory formation

Johansen J.P., Diaz-Mataix L., Hamanaka H., Ozawa T., Ycu E., Koivumaa J., Kumar A., Hou M., Deisseroth K., Boyden E.S., LeDoux J.E. (2014) Hebbian and neuromodulatory mechanisms interact to trigger associative memory formation, Proceedings of the National Academy of Sciences 111(51):E5584–E5592.

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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.


Understanding normal and pathological brain computations

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