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Anna Beleyer

Neurocentre Magendie, Inserm, University of Bordeaux

Title

Neural coding of anxiety and emotional valence in circuits of the insular cortex

Abstract

The response of the insular cortex (IC) and amygdala to stimuli of positive and negative valence were found to be altered in patients with anxiety disorders. However, the coding properties of neurons controlling anxiety and valence in this brain region remained unknown.

To assess anxiety- and valence-related behaviors we used established behavioral assays including the elevated plus maze (EPM), the open field test (OFT), sucrose and quinine consumption, mild footshock as well as tail suspension. We combined photometry recordings, pharmacology and optogenetics in mice, as well as viral tracing and ex vivo electrophysiology, to dissect the role of four insular neural populations. We focused our analysis on three aspects of neural diversity: [1] topographical diversity by comparing the anterior and posterior insular cortex (aIC and pIC), [2] diversity based molecular markers (glutamate, GABA as well as serotonin and dopamine receptors) and [3] diversity based on the projection target, focusing on insula neurons targeting the basolateral amygdala (BLA).

First, we uncover that glutamatergic projection neurons in aIC are more active in anxiogenic spaces, while the pIC did not show changes in activity. Interestingly, in a pathological model of anxiety, induced by a high fat diet, we revealed an upregulation of the aIC, suggesting that alteration of the coding properties of projection neurons of the aIC contribute to the pathophysiology of anxiety disorders. We then characterized the monosynaptic aIC to BLA connection, and employed projection-specific optogenetics, to reveal anxiogenic properties of aIC-BLA neurons in anxiety-related behaviors. Then, using projection specific photometry recordings, we identified that aIC-BLA neurons are more active in anxiogenic spaces, and in response to aversive stimuli.

Together, our findings show that negative valence, as well as anxiety-related information and behaviors are encoded by aIC glutamatergic neurons and more specifically within aIC-BLA glutamatergic circuit.

Biosketch

Anna Beyeler received her undergraduate degree in Biochemistry from the University of Bordeaux in 2006. Her expertise in electrophysiology roots in her doctoral training in the same university, after what she joined the Picower Institute for Learning and Memory (MIT) as post-doctoral fellow. There, she identified circuit and synaptic mechanisms of emotions in the amygdala, underlying memory formation and retrieval of positive and negative associations. After five years abroad, she started her lab in the Neurocentre Magendie within the vibrant Neuroscientific community of Bordeaux. Since then, her team is studying the contribution of circuits of the insular cortex to emotional valence and anxiety, as well as the alteration of those circuits in pre-clinical models of psychiatric disorders. They use a wide panel of techniques including fiber photometry recordings, in vivo and ex vivo electrophysiology, opto- and chemo-genetics, along with cutting-edge whole-brain circuit mapping. In 2020, Dr. Beyeler has been tenured as a principal investigator by the French Institute of Health (INSERM). She received the Avenir fund of INSERM, and numerous grants including from ANR, FRM or the ‘Cercle FSER’. She is also an associate member of the American College of Neuropsychopharmacology (ACNP), a member of the FENS-Kavli Network, and an ambassador of the ALBA network for diversity in Neuroscience.



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