Disinhibitory amygdala microcircuits for aversive learning

Learning and memory are fundamental neuronal processes that areessential for behavioural adaptations driven by unexpected positive or negativeexperiences in an ever-changing environment. While the functional role and plasticity mechanisms ofprojection neurons during associative learning have been extensively studied, to date, little is known about the contributions of local interneurons. Using fear conditioning as a model system, we combine deep brain calcium imaging and optogenetic manipulations in freely behaving mice to study the functional contribution of amygdala interneuron subtypes to associative learning. We find that interactions between distinct inhibitory interneurons can gate behaviourally relevant, salient stimuli to instruct plastic changes in neighbouring excitatory amygdala projection neurons. Furthermore, responses of distinct interneurons are highly plastic and shift from the instructive to the predictive cue upon memory formation. This novel form of adaptive disinhibitory gating allows to discriminate unexpected, important from irrelevant information, and might be a general dynamic circuit motif to trigger stimulus-specific learning, thereby ensuring appropriate behavioural adaptations to salient events.



I studied Human Biology at the University of Marburg and received my PhD in Neurophysiology in 2012. In a collaborative project in the laboratory of Jochen Roeper at the University of Frankfurt with Eleanor Simpson and Eric Kandel at Columbia University New York, I investigated the neural circuit mechanisms of dopaminergic dysregulation in schizophrenia. I then joined the laboratory of Andreas Lüthi at the Friedrich Miescher Institute for Biomedical Research in Basel as a postdoctoral fellow. Supported by a NARSAD Young Investigator Award, I focussed my research on the dissection of inhibitory amygdala microcircuits in fear learning and anxiety using a combination of deep brain imaging, electrophysiology and optogenetic approaches. Since February 2018, I am hosted by Scott Sternson’s lab as a visiting scientist at HHMI Janelia Research Campus to address how genetically-defined amygdala neurons encode information during different behavioural and metabolic states.

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