Adaptive disinhibitory gating by VIP interneurons permits associative learning
Nat Neurosci. 2019-10-21; 22(11): 1834-1843
DOI: 10.1038/s41593-019-0508-y
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Krabbe S(#)(1), Paradiso E(#)(1)(2), d’Aquin S(1)(3), Bitterman Y(1), Courtin
J(1), Xu C(1)(4), Yonehara K(1)(5), Markovic M(1)(3), Müller C(1), Eichlisberger
T(1), Gründemann J(6)(7), Ferraguti F(8), Lüthi A(9)(10).
Author information:
(1)Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
(2)Department of Pharmacology, Medical University of Innsbruck, Innsbruck,
Austria.
(3)University of Basel, Basel, Switzerland.
(4)Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China.
(5)Danish Research Institute of Translational Neuroscience – DANDRITE,
Department of Biomedicine, Nordic-EMBL Partnership for Molecular Medicine,
Aarhus University, Aarhus, Denmark.
(6)Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
.
(7)Department of Biomedicine, University of Basel, Basel, Switzerland.
.
(8)Department of Pharmacology, Medical University of Innsbruck, Innsbruck,
Austria. .
(9)Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
.
(10)University of Basel, Basel, Switzerland. .
(#)Contributed equally
Comment in
Nat Neurosci. 2019 Nov;22(11):1747-1748.
Learning drives behavioral adaptations necessary for survival. While plasticity
of excitatory projection neurons during associative learning has been
extensively studied, little is known about the contributions of local
interneurons. Using fear conditioning as a model for associative learning, we
found that behaviorally relevant, salient stimuli cause learning by tapping into
a local microcircuit consisting of precisely connected subtypes of inhibitory
interneurons. By employing deep-brain calcium imaging and optogenetics, we
demonstrate that vasoactive intestinal peptide (VIP)-expressing interneurons in
the basolateral amygdala are activated by aversive events and provide a
mandatory disinhibitory signal for associative learning. Notably, VIP
interneuron responses during learning are strongly modulated by expectations.
Our findings indicate that VIP interneurons are a central component of a dynamic
circuit motif that mediates adaptive disinhibitory gating to specifically learn
about unexpected, salient events, thereby ensuring appropriate behavioral
adaptations.