Synapses and neural circuits in behaviour

The general aim of the team is to understand how cortical synaptic circuits process and encode sensory and contextual information . We investigate in parallel the CA3 region of the hippocampus and the gustatory cortex (GC). The main strength and originality of our research lies in the systematic back-and-forth interrogation of synapses and circuits ex vivo at a molecular and cellular level, and in vivo in the context of intact neural circuits in behaving mice.

Processing and storage of information depend on multiple mechanisms, from activity-dependent plasticity processes with distinct temporal dynamics to integration of different inputs along the dendritic arborization. We will focus on the mechanisms and integrated consequences of short-term presynaptic plasticity at identified cortical synapses. Presynaptic plasticity occurs within a short- term (seconds to minutes) and long-term (up to hours) time frame at thalamo-cortical and cortico-thalamic synapses, as well as at mossy fiber synapses in CA3. Presynaptic plasticity is postulated to be powerful in controlling synaptic cortical circuits. However direct evidence for a role in controlling sensory and contextual information processing is lacking.

Synaptic alteration is a strong predictor of cognitive decline in Alzheimer’s disease (AD). We propose to explore presynaptic failure as a physiopathological determinant of AD pathology. We will use genetic tools and electrophysiology in mice to better understand the physiological and pathological role of the Amyloid Precursor Protein (APP), a central protein in AD, which is abundantly expressed in presynaptic compartments. In parallel we will implement innovative gene targeting methods applied to human organotypic cortical slices in combination with electrophysiology and high-resolution imaging.

The team has engaged into a translational project targeting aberrantly expressed KARs in temporal lobe epilepsy, in collaboration with Valérie Crépel (Inserm, Marseille). Christophe Mulle is one of the scientific founders of Corlieve Therapeutics (www.corlieve.com), a biotech company which aims at finding new therapies to cure intractable temporal lobe epilepsy. The methodology includes work on acute and organotypic human hippocampal and cortical slices from patients with intractable TLE.

Expertise: Synaptic biology, Hippocampus, Insular cortex, Memory, Sensory processing / Gustation, Alzheimer’s disease, Temporal lobe epilepsy – gene therapy

Techniques: In vivo gene transfer, Ex vivo electrophysiology (patch-clamp recordings), In vivo electrophysiology (patch-clamp, silicone probe recordings), Confocal and two-photon cellular imaging, Optogenetics and chemogenetics, Mouse behaviour