A disinhibitory microcircuit for associative fear learning in the auditory cortex

被引:607
作者
Letzkus, Johannes J. [1 ]
Wolff, Steffen B. E. [1 ,2 ]
Meyer, Elisabeth M. M. [1 ,2 ]
Tovote, Philip [1 ]
Courtin, Julien [3 ]
Herry, Cyril [3 ]
Luethi, Andreas [1 ]
机构
[1] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland
[2] Univ Basel, CH-4003 Basel, Switzerland
[3] INSERM, U862, F-33077 Bordeaux, France
基金
瑞士国家科学基金会;
关键词
GABAERGIC CELL SUBTYPES; LAYER-I INTERNEURONS; RAT NEOCORTEX; GABA RELEASE; PLASTICITY; NEURONS; MODULATION; INHIBITION; RECEPTORS; AMYGDALA;
D O I
10.1038/nature10674
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:331 / U76
页数:7
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