PT  - JOURNAL ARTICLE
AU  - Ludovic Calandreau
AU  - Pierre Trifilieff
AU  - Nicole Mons
AU  - Laurence Costes
AU  - Marc Marien
AU  - Aline Marighetto
AU  - Jacques Micheau
AU  - Robert Jaffard
AU  - Aline Desmedt
TI  - Extracellular Hippocampal Acetylcholine Level Controls Amygdala Function and Promotes Adaptive Conditioned Emotional Response
AID  - 10.1523/JNEUROSCI.3713-06.2006
DP  - 2006 Dec 27
TA  - The Journal of Neuroscience
PG  - 13556--13566
VI  - 26
IP  - 52
4099  - http://www.jneurosci.org/content/26/52/13556.short
4100  - http://www.jneurosci.org/content/26/52/13556.full
SO  - J. Neurosci.2006 Dec 27; 26
AB  - Ample data indicate that tone and contextual fear conditioning differentially require the amygdala and the hippocampus. However, mechanisms subserving the adaptive selection among environmental stimuli (discrete tone vs context) of those that best predict an aversive event are still elusive. Because the hippocampal cholinergic neurotransmission is thought to play a critical role in the coordination between different memory systems leading to the selection of appropriate behavioral strategies, we hypothesized that this cholinergic signal may control the competing acquisition of amygdala-mediated tone and contextual conditioning. Using pavlovian fear conditioning in mice, we first show a higher level of hippocampal acetylcholine release and a specific pattern of extracellular signal-regulated kinase 1/2 (ERK1/2) activation within the lateral (LA) and basolateral (BLA) amygdala under conditions in which the context is a better predictor than a discrete tone stimulus. Second, we demonstrate that levels of hippocampal cholinergic neurotransmission are causally related to the patterns of ERK1/2 activation in amygdala nuclei and actually determine the selection among the context or the simple tone the stimulus that best predicts the aversive event. Specifically, decreasing the hippocampal cholinergic signal not only impaired contextual conditioning but also mimicked conditioning to the discrete tone, both in terms of the behavioral outcome and the LA/BLA ERK1/2 activation pattern. Conversely, increasing this cholinergic signal not only disrupted tone conditioning but also promoted contextual fear conditioning. Hence, these findings highlight that hippocampal cholinergic neurotransmission controls amygdala function, thereby leading to the selection of relevant emotional information.