Section: Research Program

Research axis 3: Computational systems biology of neurons and astrocytes

Understanding neuronal plasticity

One of our main achievements concerns the study of synaptic plasticity in the the basal ganglia, the locus of procedural learning (the learning of skills and habits) and reinforcement learning. We have been carrying out joint experimental-modeling research to decipher the signaling pathways that underlay synaptic plasticity in this brain structure [49], [50]. This result is a significant advance for the understanding of synaptic plasticity because it shows that plasticity can be triggered even with low activity levels. In related threads of research, we have also studied the molecular basis of intrinsic plasticity [66] or the adult neurogenesis [66].

Biophysical models of astrocyte signaling

Neurons represent roughly half of the brain cells. The other part is made of glial cells, that include e.g. microglia, oligodendrocytes or astrocytes. The role of glial cells in cognition, learning or memory is a new field of research in neuroscience. We have developed reference mathematical models in the field, focusing on intra- and inter-cellular astrocyte calcium signals and astrocyte-to-neurons signaling via neuro- and glio-transmitters [67], [52], [62], [90]. We have initiated a modeling and theoretical study of the modulation of neuronal plasticity by astrocyte signaling [51].

Motor model for perceptive neural coding

In animal acoustic perception, the canonical representation of sound is through Fourier decomposition via a spectrographic representation. While generic, this approach does not take into account the (probable) tuning of neurons to familiar sound and therefore ad-hoc sound statistics. We have proposed an alternative view where sound representation is based on the motor representation needed to produce the acoustic output. In the context of songbirds, we proposed mechanical models that reproduce bird vocalization using muscles contractions dynamics. Part of auditory neural tuning is probably focused on decoding vocalization of endogenous individuals in the context of a social network. We have developed a series of analysis tools to identify acoustic social networks of Zebra Finches and applied them to the study of small bird groups in the lab [70], [71], [88], [53], [54].

Current Objectives

Research axis 3 will continue but with considerable modifications. We are carrying on work on synaptic plasticity in the basal ganglia focusing on the modulation of synaptic plasticity by neuromodulators like dopamine. In particular, understanding the impact of dopamine signaling in the basal ganglia could provide us with significant advances in dopamine-related pathologies (Parkinson's, addictions...). Regarding the work on astrocytes, we will concentrate our efforts on the deciphering of calcium signaling in the finest astrocyte branchlets that are expected to be the locus of interactions with the neurons. Our objective is to uncover how the spatial organization of the implied signaling molecules impacts the signaling between the synapse and the astrocyte. To obtain experimental data related to this spatial intracellular organization, we will initiate several new collaborations with experimental neuroscientists.