Defense in english
Thesis supervisor: Frédéric Gambino
Functional characterization of Amygdala projections to motor related cortices during adaptive action-selection
Animals daily face complex situations that require adapted responses for surviving. The process of evaluating the available actions and selecting the one that appears the most relevant is called “action-selection”. It requires prior building of a fine mental model that associate actions to their outcomes, often via a process of “reinforcement learning”. Despite pieces of evidence about several brain regions with neural activity correlating with choice, the circuit and neuronal mechanisms that select actions remain discussed. Recent studies highlight the secondary motor cortex (MOs), at the interface of sensory integration and motor processing, as a credible candidate for computing action-selection.
Indeed, neural activity states predicting choice have been unveiled in the MOs of rodents and its inactivation biases the selection of actions. These studies almost exclusively focused on expert animals but information about how actions are encoded in naive animals and during learning are still lacking.
In a first study (Aime*, Augusto*, Kouskoff et al., 2020), we have highlighted that the MOs receives inputs from the Basolateral Amygdala (BLA), a structure known for its importance in associative learning. We have shown that BLA inputs to the MOs facilitate the discrimination of sounds associated to different outcomes in the context of associative fear learning. In a similar way, one could imagine that the BLA provides associative signals to help MOs discriminate actions with positive values.
A major aim of the present doctoral work is the characterization of the role of these BLA-to-MOs projections during the learning of rewarding actions. To address this goal, we first developed a rewarding, self-driven action-selection paradigm for head-restrained mice allowing chronic two-photon microscopy of neuronal compartments through the different steps of learning. Using somatic calcium imaging and optogenetic, we have highlighted the implication of MOs in performing the task. Then, we have imaged and analyzed the activity of specific BLA boutons connecting to MOs over weeks of behavior, a technical challenge (because of the small size of boutons and weak signals) rarely undertaken so far. Altogether, the results presented in this thesis provide both novel evidences for the role of MOs in action-selection and for the importance of BLA to MOs projections for associative learning.
Action-selection / Basolateral Amygdala / Decision / Secondary motor cortex / Reinforcement learning
Vladimir Kouskoff*, Nicolas Chenouard*, Elisabete Augusto, Aron De Miranda, and Frédéric Gambino. BLA-to-FrA axons set online action representation during value-based reinforcement learning. (in prep.)
Elisabete Augusto*, Vladimir Kouskoff, Nicolas Chenouard and Frédéric Gambino. Prefrontal control of choice during learning of a value-based decision-making task. (pending submission)
Mattia Aime*, Elisabete Augusto*, Vladimir Kouskoff, Tiago Campelo, Christelle Martin, Yann Humeau, Nicolas Chenouard, Frédéric Gambino. The integration of Gaussian noise by long-range amygdala inputs in frontal circuit promotes fear learning in mice. (Elife 2020) doi.org/10.7554/eLife.62594
Roman Serrat, Ana Covelo, Vladimir Kouskoff, Sebastien Delcasso, Andrea Ruiz, Nicolas Chenouard, Carol Stella, Corinne Blancard, Benedicte Salin, Francisca Julio-Kalajzić, Astrid Cannich, Federico Massa, Marjorie Varilh, Severine Deforges, Laurie M. Robin, Diego De Stefani, Arnau Busquets-Garcia, Frédéric Gambino, Anna Beyeler, Sandrine Pouvreau* and Giovanni Marsicano*. Astroglial calcium transfer from endoplasmic reticulum to mitochondria determines synaptic integration. (in revision) doi.org/10.1101/2020.12.08.415620
Stéphane Pagès*, Nicolas Chenouard*, Ronan Chéreau, Vladimir Kouskoff, Frédéric Gambino# and Anthony Holtmaat#. An increase in dendritic plateau potentials is associated with experience-dependent cortical map reorganization. (PNAS 2021) doi.org/10.1073/pnas.2024920118
Tomàs Jordà-Siquier, Melina Petrel, Vladimir Kouskoff, Fabrice Cordelières, Susanne Frykman, Ulrike Müller, Christophe Mulle, Gaël Barthet. APP accumulates around dense-core amyloid plaques with presynaptic proteins in Alzheimer’s disease brain. (in revision) doi.org/10.1101/2020.10.16.342196
Tiago Campelo, Elisabete Augusto, Nicolas Chenouard, Aron de Miranda, Vladimir Kouskoff, Come Camus, Daniel Choquet* and Frédéric Gambino*. AMPAR-Dependent Synaptic Plasticity Initiates Cortical Remapping and Adaptive Behaviors during Sensory Experience. (Cell reports 2020) doi.org/10.1016/j.celrep.2020.108097
Bureau Ingrid : Chargée de recherche (Marseille) – Rapporteur
Popa Daniela : Directrice de recherche (Paris) – Rapporteur
Leblois Arthur : Chargé de recherche (Bordeaux) – Examinateur
Wolff Mathieu : Directeur de recherche (Bordeaux) – Examinateur