Institut NeuroPSI - UMR9197
CNRS Université Paris-Saclay
Campus CEA Saclay
Saclay, FRANCE

Claire Eschbach

Assistant Professor Paris-Saclay University
Molecular Genetics of Circadian Rhythms

claire.eschbach universite-paris-saclay.fr
+33(0)1 69 82 34 48, room 2118
ORCID : 0000-0002-8092-3440

Research

The formation of flexible memory is a key ability that allows tracking the value of a choice outcome for adaptive decision in dynamic environments. How do brain circuits compute such values? This question is central to understanding how multiple behavioral disorders develop due to the awry computation of values associated with choices, e.g. in drug addiction. In both mammals and insects, associative circuits allow the constant update of memory upon repetitive experience. Their function relies on modulatory teaching signals delivered by dopaminergic inputs, which themselves receive recurrent connections from the output of the circuit. Many questions remain regarding the mechanisms for the computation of learned value, notably about the role of recurrent connections within the circuits to continue or arrest the gating of synaptic plasticity and the molecular pathways following dopamine signals that set a specific level of plasticity. I study these questions in the associative circuit within the larval brain of Drosophila melanogaster.

My research considers two main mechanisms:

  1. On one hand, the role of recurrent connections in adjusting dopamine-gated plasticity. The hypotheses I focus on are based on reinforcement learning theories as well as on knowledge from the larval brain connectome (entirely recontructed and published in Winding et al., Science 2023). Using advanced neurogenetics approach, I transiently manipulate dopamine reinforcing neurons as well as the neurons projecting feedback onto dopamine neurons, while testing the effect of this manipulation on fine-tuning learned behaviors and on dopamine responses to unpredicted or predicted stimuli.

  2. On the other hand, the role of different dopamine receptors and second messengers to implement synaptic plasticity over the course of training. Here, I base my hypotheses on previous findings on the involvement of distinct types of dopamine receptors expressed in the same memory cells in setting associative memories of different kinds. I plan to use RNA interference techniques to knock down specific receptors in specific neurons and set up in vivo imaging of 2nd messengers.

Drosophila larva uniquely permits a combination of sophisticated, multi-scale, approaches. With online tracking, specific genetic targeting of neurons (to e.g. activate, silence, or image neuronal activity), computational modelling of networks, and the use of a detailed connectome as a road map, we can study the way recurrent networks implement reinforcement learning to an unprecedented level of precision.

upper left: Localisation of Drosophila larva’s CNS

upper right: Genetic tools to access individual pair of dopaminergic neurons (modified from Eschbach et al., Nature Neuro 2020)

 lower left: Chamber for the training of groups of larvae. Red light is to depolarise dopaminergic neurons via red-shifted channelrhodpsin CsChrimson. The chamber is temperature-controlled, allowing the use of thermogenetics to inactivate neurons.

 lower right: Microfluidic device used for in vivo imaging neurons during odor exposure and/or optogenetic activation. That way, individuals can be trained under the microscope.
(pictures are modified from Si et al., Neuron 2019)

Funding

  • 2023-2024 Fyssen Foundation
  • 2024-2027 ATIP-Avenir

Teaching at Paris Saclay University

  • Neuroscience (licence & master level)
  • Animal physiology, Biology-chemistry (licence level)
  • Scientific methodology, scientific English (licence level)

Publications

Journal articles

2021

ref_biblio
Claire Eschbach, Akira Fushiki, Michael Winding, Bruno Afonso, Ingrid Andrade, et al.. Circuits for integrating learned and innate valences in the insect brain. eLife, 2021, 10, pp.10:e62567. ⟨10.7554/eLife.62567⟩. ⟨hal-04193586⟩
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https://hal.science/hal-04193586/file/Circuits-integrating-learned-an-innate-valences-62567-v3.pdf BibTex

2020

ref_biblio
Claire Eschbach, Akira Fushiki, Michael Winding, Casey Schneider-Mizell, Mei Shao, et al.. Recurrent architecture for adaptive regulation of learning in the insect brain. Nature Neuroscience, 2020, 23 (4), pp.544-555. ⟨10.1038/s41593-020-0607-9⟩. ⟨hal-04193610⟩
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ref_biblio
Claire Eschbach, Marta Zlatic. Useful road maps: studying Drosophila larva’s central nervous system with the help of connectomics. Current Opinion in Neurobiology, 2020, 65, pp.129-137. ⟨10.1016/j.conb.2020.09.008⟩. ⟨hal-04193602⟩
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2018

ref_biblio
Birgit Michels, Hanna Zwaka, Ruth Bartels, Oleh Lushchak, Katrin Franke, et al.. Memory enhancement by ferulic acid ester across species. Science Advances , 2018, 4 (10), pp.eaat6994. ⟨10.1126/sciadv.aat6994⟩. ⟨hal-04204818⟩
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Timo Saumweber, Astrid Rohwedder, Michael Schleyer, Katharina Eichler, Yi-Chun Chen, et al.. Functional architecture of reward learning in mushroom body extrinsic neurons of larval Drosophila. Nature Communications, 2018, 9 (1), pp.1104. ⟨10.1038/s41467-018-03130-1⟩. ⟨hal-04193626⟩
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2017

ref_biblio
Maria Almeida-Carvalho, Dimitri Berh, Andreas Braun, Yi-Chun Chen, Katharina Eichler, et al.. The Ol1mpiad: concordance of behavioural faculties of stage 1 and stage 3 Drosophila larvae. Journal of Experimental Biology, 2017, 220 (13), pp.2452-2475. ⟨10.1242/jeb.156646⟩. ⟨hal-04193647⟩
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ref_biblio
Katharina Eichler, Feng Li, Ashok Litwin-Kumar, Youngser Park, Ingrid Andrade, et al.. The complete connectome of a learning and memory centre in an insect brain. Nature, 2017, 548 (7666), pp.175-182. ⟨10.1038/nature23455⟩. ⟨hal-04193636⟩
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Birgit Michels, Timo Saumweber, Roland Biernacki, Jeanette Thum, Rupert Glasgow, et al.. Pavlovian Conditioning of Larval Drosophila: An Illustrated, Multilingual, Hands-On Manual for Odor-Taste Associative Learning in Maggots. Frontiers in Behavioral Neuroscience, 2017, 11, pp.45. ⟨10.3389/fnbeh.2017.00045⟩. ⟨hal-04193657⟩
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2011

ref_biblio
Claire Eschbach, Carmen Cano, Hannah Haberkern, Karla Schraut, Chonglin Guan, et al.. Associative learning between odorants and mechanosensory punishment in larval Drosophila. Journal of Experimental Biology, 2011, 214 (23), pp.3897-3905. ⟨10.1242/jeb.060533⟩. ⟨hal-04205893⟩
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Claire Eschbach, Katrin Vogt, Michael Schmuker, Bertram Gerber. The Similarity between Odors and Their Binary Mixtures in Drosophila. Chemical Senses, 2011, 36 (7), pp.613-621. ⟨10.1093/chemse/bjr016⟩. ⟨hal-04193669⟩
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Thomas Niewalda, Thomas Völler, Claire Eschbach, Julia Ehmer, Wen-Chuang Chou, et al.. A Combined Perceptual, Physico-Chemical, and Imaging Approach to ‘Odour-Distances’ Suggests a Categorizing Function of the Drosophila Antennal Lobe. PLoS ONE, 2011, 6 (9), pp.e24300. ⟨10.1371/journal.pone.0024300⟩. ⟨hal-04193696⟩
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2009

ref_biblio
Roxana Josens, Claire Eschbach, Martin Giurfa. Differential conditioning and long-term olfactory memory in individual Camponotus fellah ants. Journal of Experimental Biology, 2009, 212 (12), pp.1904-1911. ⟨10.1242/jeb.030080⟩. ⟨hal-04193703⟩
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