Membrane trafficking in hypothalamic neurons
Program lead: Karl Vivot (CRCN Inserm).
What we have shown so far
- CaMK1D in AgRP neurons mediates ghrelin’s orexigenic action: Genetic disruption of Camk1d blunts ghrelin-evoked feeding, reduces body-weight gain and protects against high-fat-diet–induced obesity in mice.
- Neuronal mechanism: In AgRP/NPY neurons, ghrelin activates CaMK1D; loss of CaMK1D dampens downstream transcriptional responses (e.g., reduced CREB phosphorylation) and the orexigenic program.
- System-level outcome: The CaMK1D pathway in AgRP neurons connects fasting signals to increased food intake and adiposity in vivo.
Project
Aim 1: Endosomal timing of energy-sensing receptors
Quantify how endosomal routing and signaling kinetics in ARC neuron classes shape immediate neuronal activity and short-term feeding outcomes.
Aim 2: Membrane-gated neuropeptide release
Test whether nanoscale membrane composition at release sites tunes vesicle priming and fusion probabilities and thereby modulates circuit output.
Aim 3: Glia→neuron lipid supply
Probe whether lipid shuttling from glia sets neuronal membrane state and energetic demand, feeding back onto circuit activity and behavior.
Key tools (selected)
- Live reporters of receptor signaling and neuronal activity in defined hypothalamic populations
- Endosome tracking and lipid-state perturbations compatible with acute physiology
- pHluorin-based neuropeptide release assays and electrophysiology
- Single-cell lipidomics around the median eminence; tracer-based glia→neuron lipid transfer
- Behavioral and metabolic readouts aligned to circuit manipulations
Public overview. Operational protocols, constructs, and parameter values are intentionally not disclosed.