A Cholinergic-Dependent Role for the Entorhinal Cortex in Trace Fear Conditioning
Journal of Neuroscience. 2009-06-24; 29(25): 8087-8093
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1. J Neurosci. 2009 Jun 24;29(25):8087-93. doi: 10.1523/JNEUROSCI.0543-09.2009.
A cholinergic-dependent role for the entorhinal cortex in trace fear
Esclassan F(1), Coutureau E, Di Scala G, Marchand AR.
(1)Centre National de la Recherche Scientifique, Centre de Neurosciences
Intégratives et Cognitives, Unité Mixte de Recherche (UMR) 5228, Talence, France.
Trace conditioning is considered a model of higher cognitive involvement in
simple associative tasks. Studies of trace conditioning have shown that cortical
areas and the hippocampal formation are required to associate events that occur
at different times. However, the mechanisms that bridge the trace interval during
the acquisition of trace conditioning remain unknown. In four experiments with
fear conditioning in rats, we explored the involvement of the entorhinal cortex
(EC) in the acquisition of fear under a trace-30 s protocol. We first determined
that pretraining neurotoxic lesions of the EC selectively impaired trace-, but
not delay-conditioned fear as evaluated by freezing behavior. A local cholinergic
deafferentation of the EC using 192-IgG-saporin did not replicate this deficit,
presumably because cholinergic interneurons were spared by the toxin. However,
pretraining local blockade of EC muscarinic receptors with the M1 antagonist
pirenzepine yielded a specific and dose-dependent deficit in trace-conditioned
responses. The same microinjections performed after conditioning were without
effect on trace fear responses. These effects of blocking M1 receptors are
consistent with the notion that conditioned stimulus (CS)-elicited,
acetylcholine-dependent persistent activities in the EC are needed to maintain a
representation of a tone CS across the trace interval during the acquisition of
trace conditioning. This function of the EC is consistent with recent views of
this region as a short-term stimulus buffer.
PMID: 19553448 [Indexed for MEDLINE]