Extracellular hippocampal acetylcholine level controls amygdala function and promotes adaptive conditioned emotional response
Journal of Neuroscience. 2006-12-27; 26(52): 13556-13566
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1. J Neurosci. 2006 Dec 27;26(52):13556-66.
Extracellular hippocampal acetylcholine level controls amygdala function and
promotes adaptive conditioned emotional response.
Calandreau L(1), Trifilieff P, Mons N, Costes L, Marien M, Marighetto A, Micheau
J, Jaffard R, Desmedt A.
(1)Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5106,
Laboratoire de Neurosciences Cognitives, 33405 Talence, France.
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
PMID: 17192439 [Indexed for MEDLINE]