title: Amygdala interneuron subtypes control fear learning through disinhibition.
abstract: Learning is mediated by experience-dependent plasticity in neuronal circuits. Activity in neuronal circuits is tightly regulated by different subtypes of inhibitory interneurons, yet their role in learning is poorly understood. Using a combination of in vivo single-unit recordings and optogenetic manipulations, we show that in the mouse basolateral amygdala, interneurons expressing parvalbumin (PV) and somatostatin (SOM) bidirectionally control the acquisition of fear conditioning--a simple form of associative learning--through two distinct disinhibitory mechanisms. During an auditory cue, PV(+) interneurons are excited and indirectly disinhibit the dendrites of basolateral amygdala principal neurons via SOM(+) interneurons, thereby enhancing auditory responses and promoting cue-shock associations. During an aversive footshock, however, both PV(+) and SOM(+) interneurons are inhibited, which boosts postsynaptic footshock responses and gates learning. These results demonstrate that associative learning is dynamically regulated by the stimulus-specific activation of distinct disinhibitory microcircuits through precise interactions between different subtypes of local interneurons.
authors.affiliation: 1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland [2] University of Basel, 4000 Basel, Switzerland [3].
authors.forename: Steffen B E
authors.initials: SB
authors.lastname: Wolff
authors.affiliation: 1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland [2].
authors.forename: Jan
authors.initials: J
authors.lastname: Gründemann
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
authors.forename: Philip
authors.initials: P
authors.lastname: Tovote
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Krabbe
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
authors.forename: Gilad A
authors.initials: GA
authors.lastname: Jacobson
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Müller
authors.affiliation: INSERM U862, Neurocentre Magendie, 146 rue Leo Saignat, 33077 Bordeaux, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Herry
authors.affiliation: Hertie Institute for Clinical Brain Research, 72076 Tübingen, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Ehrlich
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
authors.forename: Rainer W
authors.initials: RW
authors.lastname: Friedrich
authors.affiliation: 1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland [2] Max-Planck Institute for Brain Research, 60438 Frankfurt, Germany. [3].
authors.forename: Johannes J
authors.initials: JJ
authors.lastname: Letzkus
authors.affiliation: 1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland [2].
authors.forename: Andreas
authors.initials: A
authors.lastname: Lüthi
mesh_terms: D000679:Amygdala / Q000166:cytology* / Q000502:physiology*; D000818:Animals; D003214:Conditioning, Classical; D004597:Electroshock; D005239:Fear / Q000502:physiology*; D006614:Hindlimb; D007266:Inhibition, Psychological; D007395:Interneurons / Q000378:metabolism*; D007858:Learning / Q000502:physiology*; D008297:Male; D051379:Mice; D062308:Optogenetics; D010320:Parvalbumins / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
chemical_list: D010320:Parvalbumins; D013004:Somatostatin