Journal Article

A disinhibitory microcircuit for associative fear learning in the auditory cortex

Lüthi, Andreas, Courtin, Julien, Wolff, Steffen B. E., Tovote, Philip, Meyer, Elisabeth M. M., Letzkus, Johannes J., Herry, Cyril

2011

Overview

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. Stimulus convergence and concomitant auditory cortex disinhibition are essential for fear learning. Sounds like fear It is generally recognized that learned behavioural responses, such as those associated with sound, involve changes within specific neural circuits. However, we are only beginning to understand how those changes are implemented and what interactions between different types of neurons within the circuits contribute to the learning process. Using classical sound-based fear-conditioning in mice as a model system, Andreas Lüthi and colleagues identify a distinct disinhibition-based circuit that is critical to learning. The neural circuit involved is not specific to auditory cortex, and may represent a general mechanism through which cholinergic neuromodulation gates cortical activity.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/378/1595/2636 / 631/378/2619 / 631/443/376 / Analysis / Animals / Auditory cortex / Auditory Cortex - cytology / Auditory Cortex - drug effects / Auditory Cortex - physiology / Biological and medical sciences / Brain / Conditioning, Classical - drug effects / Conditioning, Classical - physiology / Control / Ear and associated structures. Auditory pathways and centers. Hearing. Vocal organ. Phonation. Sound production. Echolocation / Electroshock / Emotional conditioning / Extremities - innervation / Extremities - physiology / Fear / Fear - drug effects / Fear - physiology / Fear - psychology / Fundamental and applied biological sciences. Psychology / Humanities and Social Sciences / Influence / Interneurons / Interneurons - cytology / Interneurons - drug effects / Interneurons - physiology / Learning in animals / Male / Mice / Mice, Inbred C57BL / Models, Neurological / multidisciplinary / Nerve Net - cytology / Nerve Net - drug effects / Nerve Net - physiology / Neural circuitry / Neural Inhibition - drug effects / Neural Inhibition - physiology / Neural Pathways - cytology / Neural Pathways - drug effects / Neural Pathways - physiology / Neurology / Neurons / Nicotinic Antagonists - pharmacology / Physiological aspects / Psychological aspects / Pyramidal Cells - drug effects / Pyramidal Cells - physiology / Receptors, Nicotinic - metabolism / Science / Vertebrates: nervous system and sense organs