Computational and Systems Neuroscience

Team Leader : Frédéric Gambino

PhD, CR CNRS - frederic.gambino@u-bordeaux.fr

Frédéric Gambino’s research goal is to understand how neuronal networks of behaving animals modulate the structure of their synaptic connections in response to learning, and how this process regulates the dynamics of representations that drive complex behaviors such as associative fear learning, decision-making, and action selection.

General objective

Our daily life is a complex chain of decisions and actions that shapes our behaviors. Individuals tend to choose the best action possible (‘action-selection’) among different alternatives through “goal-directed” decision-making. To learn and achieve an optimal behavior, individuals must: (i) Predict the potential cost (e.g. risk) and benefit (e.g. reward) that might occur as a consequence of an action (‘outcome’). This ‘action-value’ function is learned from the causal consequences of an action (‘action-outcome’ association), and the subjective value of different outcomes (‘outcome-value’ associations); (ii) Compare ‘action value’ functions and select the action with the greatest value. The probability of selecting one of two choices is called ‘action-selection’ and determined by the difference in their ‘action value’ functions; (iii) Update the ‘action-value’ function according to the difference between the predicted and the obtained reward. Development of neuroeconomics as well as maladaptive decision-making found in many neuropsychiatric disorders highlight the crucial importance of this process.

The prefrontal cortex (PFC) appears to be well suited to organize such action-selection. However, despite the growing interest of ‘action-outcome’ and ‘outcome-value’ associations over the past few years, the neuronal correlates of choices that drive goal-directed ‘action-selection’ as well as the synaptic underpinnings have been largely neglected. By developing new methods and sophisticated strategies in behaving mice, we aim to resolve several outstanding questions:

Given that the comparison between choice alternatives should occur in the cortex as a precursor of choice and action, are multiple choices represented in the cortex by specific patterns of cell activation? Are they pre-existing or encoded through learning?
Given that the reward values are supposed to be encoded in several cortical structures through the help of subcortical structures, how are these different systems interconnected, and how do they cooperate to implement action values in the cortex and further influence choice? How are components of valuation encoded in the cortex, and to what extent do they modulate action representation?
Given that maladaptive decision-making is found in many psychiatric disorders including autism, are the synaptic and cellular underpinnings of decision-making altered in our mouse model of autism? How does the brain integrate previous memory traces to arbitrate between conflicting value information?

This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 677878)

News

Dendritic spikes and cortical remapping, PNAS February 2021

An increase in dendritic plateau potentials is associated with experience-dependent cortical map reorganization

Here we describe a mechanism for cortical map plasticity. Classically, representational map changes are thought to be driven by changes within cortico-cortical circuits, e.g., Hebbian plasticity of synaptic circuits that lost vs. maintained an excitatory drive from the first-order thalamus, possibly steered by neuromodulatory forces from deep brain regions. Our work provides evidence for an additional gating mechanism, provided by plateau potentials, which are driven by higher-order thalamic feedback. Higher-order thalamic neurons are characterized by broad receptive fields, and the plateau potentials that they evoke strongly facilitate long-term potentiation and elicit spikes. We show that these features combined constitute a powerful driving force for the fusion or expansion of sensory representations within cortical maps.

Legend: We provide evidence for a gating mechanism of cortical remapping, provided by plateau potentials, which are driven by higher-order thalamic feedback. Higher-order thalamic neurons are characterized by broad receptive fields, and the plateau potentials that they evoke strongly facilitate long-term potentiation and elicit spikes. We show that these features combined constitute a powerful driving force for the fusion or expansion of sensory representations within cortical maps.

Authors: Stéphane Pagès, Nicolas Chenouard, Ronan Chéreau, Vladimir Kouskoff, Frédéric Gambino, and Anthony Holtmaat

=> PNAS March 2, 2021 118 (9) e2024920118; https://doi.org/10.1073/pnas.2024920118

=> Contacts: Nicolas Chenouard & Frédéric Gambino

Frédéric Gambino winner of the ERC Consolidator 2021 - July 2022

Winner of an ERC starting grant in 2016 with the NEUROGOAL project, Frédéric Gambino has just been awarded an ERC consolidator with the MOTORHEAD project.
Congratulations!

Contact: Frédéric Gambino

- See the Bordeaux Neurocampus website here (English)
- See the CNRS INSB website here (French)

Dynamic interplay between thalamic activity & Cajal-Retzius... Cell Reports, April 2022

Dynamic interplay between thalamic activity & Cajal-Retzius cells regulates the wiring of cortical layer1

Cortical wiring relies on guidepost cells and activity-dependent processes that are thought to act sequentially. Here, we show that the construction of layer 1 (L1), a main site of top-down integration, is regulated by crosstalk between transient Cajal-Retzius cells (CRc) and spontaneous activity of the thalamus, a main driver of bottom-up information. While activity was known to regulate CRc migration and elimination, we found that prenatal spontaneous thalamic activity and NMDA receptors selectively control CRc early density, without affecting their demise. CRc density, in turn, regulates the distribution of upper layer interneurons and excitatory synapses, thereby drastically impairing the apical dendrite activity of output pyramidal neurons. In contrast, postnatal sensory-evoked activity had a limited impact on L1 and selectively perturbed basal dendrites synaptogenesis. Collectively, our study highlights a remarkable interplay between thalamic activity and CRc in L1 functional wiring, with major implications for our understanding of cortical development.

=> Authors: Genescu I, Martinez MA, Kouskoff V, Chenouard N, Mailhes-Hamon C, Cartonnet H, Lokmane L, Rijli FM, López-Bendito G, Gambino F and Garel S.

=> Cell Reports, April 12, 2022 ; 39(2) : 110667. ; https://doi.org/10.1016/j.celrep.2022.110667

=> Contacts: Frederic Gambino

Selected Publications

Genescu I, Martinéz MA, Kouskoff V, Chenouard N, Mailhes-Hamon C, Cartonnet H, Lokmane L, Rijli FM, López-Bendito G, Gambino F and Garel S.

Dynamic interplay between thalamic activity and Cajal-Retzius cells regulates the wiring of cortical layer 1. Cell Reports (2022)
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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)
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Aime M, Augusto E, Kouskoff V, Campelo T, Martin C, Humeau Y, Chenouard N, Gambino F

The integration of Gaussian noise by long-range amygdala inputs in frontal circuit promotes fear learning in mice eLife (2020)
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Campelo T, Augusto E, Chenouard N, de Miranda A, Kouskoff V, Camus C, Choquet D, Gambino F

AMPAR-Dependent Synaptic Plasticity Initiates Cortical Remapping and Adaptive Behaviors during Sensory Experience Cell Reports (2020)
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Gambino F, Choquet D

Eyes Wide Open on AMPAR Trafficking during Motor Learning Neuron (2020)
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Augusto E, Gambino F

Can NMDA Spikes Dictate Computations of Local Networks and Behavior? Front Mol Neurosci (2019)
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Gambino F, Pagès S, Kehayas V, Baptista D, Tatti R, Carleton A, Holtmaat A

Sensory-evoked LTP driven by dendritic plateau potentials in vivo Nature (2014)
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Pouchelon G, Gambino F, Bellone C, Telley L, Vitali I, Lüscher C, Holtmaat A, Jabaudon D

Modality-specific thalamocortical inputs instruct the identity of postsynaptic L4 neurons Nature (2014)
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Gambino F, Holtmaat A

Spike-timing-dependent potentiation of sensory surround in the somatosensory cortex is facilitated by deprivation-mediated disinhibition Neuron (2012)
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Gambino F, Holtmaat A

Synapses let loose for a change: inhibitory synapse pruning throughout experience-dependent cortical plasticity Neuron (2012)
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Members

« Researcher »

GAMBINO Frederic

Researcher

frederic.gambino@u-bordeaux.fr

+33533514701

« Technical Staff »

ALONSO Lucille	Technical staff	lucille.alonso@u-bordeaux.fr	+33533514700
CADORET Marie-Anne	Technical staff	marie-anne.cadoret@u-bordeaux.fr	+33533514701
LOUIS Alexy	Technical staff	alexy.louis@etu.u-bordeaux.fr	+33533514700