Ion Channel and Synaptic Neurobiology

Dynamics of neuronal excitability and epilepsy

A large part of our research activity is devoted to characterizing interactions between synaptic and intrinsic plasticity. We established that learning rules defined for synaptic transmission are valid for plasticity of dendritic integration in CA1 pyramidal neurons. We demonstrated that GABAergic interneurons also express plasticity of intrinsic excitability. We are exploring i) the activity-dependent regulation of Kv1 channels, ii) the mechanisms underlying intrinsic plasticity induced in parallel with synaptic long-term depression and iii) the role of intrinsic plasticity in amblyopia.

We are also exploring the factors determining neuronal synchronization at two strategic points: the synapse and the axon initial segment. We established that the synaptic delay depends on release probability and presynaptic spike waveform. Thus, synaptic delay is modified during several forms of short- and long-term synaptic plasticity.
We also demonstrated the role of voltage trajectories preceding the spike in temporal precision of spike firing. We also explore the role of inhibitory synaptic activity in the precision of neuronal discharge.

Finally, our work also examines how voltage-gated ion channels in the axon determine information processing in hippocampal and neocortical circuits. We aim to determine the axonal mechanisms of analog-digital modification of synaptic strength.

Molecular mechanisms of neurotransmitter release

We are interested in 3 parallel research axes:

1. We are particularly interested in the implication of the V-ATPase subunits “V0c” and “V0d” in the modulation of neurotransmitter release.
2. We are interested in studying the effect of LGI1 and its autoantibodies on the regulation of Kv1 channel expression and the consequences on neuronal excitability and synaptic transmission.
3. Through cellular biology, biochemistry and modeling approaches we aim at deciphering the molecular mechanisms that govern the recognition of botulinum neurotoxins by their neuronal receptors.

Robustness of excitability

Our work focuses on the molecular mechanisms underlying the robustness of neuronal activity. A number of studies have demonstrated that neurons are able to maintain stable pattens of activity in spite of the numerous internal and external perturbations they are constantly submitted to. Pharmacological manipulation or sensory deprivation experiments have shown that synaptic and ion channel properties are dynamically regulated in order to maintain a stable level of activity (for review see Turrigiano, Cell, 2008). Moreover, a growing number of studies have demonstrated that the chronic deletion of ion channels (KO animals) might only slightly alter neuronal activity (see for instance Swensen & Bean, J. Neurosci. 2005), illustrating the ability of neurons to compensate for the random mutations that spontaneously occur in the genome. It seems rather obvious that this stability depends on the dynamic regulation of the numerous ion channel subtypes (ligand-gated or voltage-gated) responsible for neuronal activity.