A disinhibitory microcircuit for associative fear learning in the auditory cortex

Johannes J. Letzkus, Steffen B. E. Wolff, Elisabeth M. M. Meyer, Philip Tovote, Julien Courtin, Cyril Herry, Andreas Lüthi
Nature. 2011-12-01; 480(7377): 331-335
DOI: 10.1038/nature10674

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1. Nature. 2011 Dec 7;480(7377):331-5. doi: 10.1038/nature10674.

A disinhibitory microcircuit for associative fear learning in the auditory

Letzkus JJ(1), Wolff SB, Meyer EM, Tovote P, Courtin J, Herry C, Lüthi A.

Author information:
(1)Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66,
CH-4058 Basel, Switzerland.

Comment in
Nat Rev Neurosci. 2012 Feb;13(2):72.

Learning causes a change in how information is processed by neuronal circuits.
Whereas synaptic plasticity, an important cellular mechanism, has been studied in
great detail, we know much less about how learning is implemented at the level of
neuronal circuits and, in particular, how interactions between distinct types of
neurons within local networks contribute to the process of learning. Here we show
that acquisition of associative fear memories depends on the recruitment of a
disinhibitory microcircuit in the mouse auditory cortex.
Fear-conditioning-associated disinhibition in auditory cortex is driven by
foot-shock-mediated cholinergic activation of layer 1 interneurons, in turn
generating inhibition of layer 2/3 parvalbumin-positive interneurons.
Importantly, pharmacological or optogenetic block of pyramidal neuron
disinhibition abolishes fear learning. Together, these data demonstrate that
stimulus convergence in the auditory cortex is necessary for associative fear
learning to complex tones, define the circuit elements mediating this convergence
and suggest that layer-1-mediated disinhibition is an important mechanism
underlying learning and information processing in neocortical circuits.

DOI: 10.1038/nature10674
PMID: 22158104 [Indexed for MEDLINE]

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