title: A disinhibitory microcircuit for associative fear learning in the auditory cortex.
abstract: 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.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland. johannes.letzkus@fmi.ch
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Letzkus
authors.forename: Steffen B E
authors.initials: SB
authors.lastname: Wolff
authors.forename: Elisabeth M M
authors.initials: EM
authors.lastname: Meyer
authors.forename: Philip
authors.initials: P
authors.lastname: Tovote
authors.forename: Julien
authors.initials: J
authors.lastname: Courtin
authors.forename: Cyril
authors.initials: C
authors.lastname: Herry
authors.forename: Andreas
authors.initials: A
authors.lastname: Lüthi
mesh_terms: D000818:Animals; D001303:Auditory Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology*; D004597:Electroshock; D005121:Extremities / Q000294:innervation / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology* / Q000523:psychology*; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D009415:Nerve Net / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D011978:Receptors, Nicotinic / Q000378:metabolism
chemical_list: D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic