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Computational and Systems Neuroscience

Team Leader : Frédéric Gambino


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)


Dendritic spikes and cortical remapping, PNAS February 2021

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

Selected Publications

  • 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)

  • Augusto E, Gambino F
  • Can NMDA Spikes Dictate Computations of Local Networks and Behavior? Front Mol Neurosci (2019)

  • 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)

  • 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)

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

  • Gambino F, Holtmaat A
  • Synapses let loose for a change: inhibitory synapse pruning throughout experience-dependent cortical plasticity Neuron (2012)


    « Researcher »

    GAMBINO Frederic Researcher +33533514701

    « Technical Staff »

    CADORET Marie-Anne Technical staff +33533514701

    « Postdoc »

    CHENOUARD Nicolas Postdoc +33533514700
    DE MIRANDA Aron Postdoc +33533514777
    KOUSKOFF Vladimir Postdoc +33533514777

    « PhD student »

    GIRAUDET Margaux PhD student +33533514700