Preliminary results :
1. Biosimulation platform (Rhenovia) :
Synapses are structures in the nervous system that permit neurons to pass electrical or chemical signals to one another and are composed of three elements:
- the presynaptic terminal, which releases neurotransmitter following an action potential in the input neuron;
- the synaptic cleft in which the neurotransmitter is released;
- the postsynaptic element belonging to the target neuron. The neurotransmitter activates receptors which transform the chemical signal into electrical and biochemical signals through the activation of ion channels and intracellular secondary messenger pathways.
Individual properties of neurotransmitter receptors such as affinity for their ligand and kinetic characteristics (activation, deactivation, desensitization) strongly influence their activation profile. In addition to these intrinsic specificities, the location within the synapse, i.e. close (synaptic) or far (extrasynaptic) from the release site will also influence the response.
The preliminary step was to study protein-protein dynamics and interactions of glutamate receptors AMPA, NMDA and metabotropic glutamate receptor (mGluR) and their subtype of receptors (NR1/NR2A and NR1/NR2B NMDAR, GluA1 and GluA2 AMPAR, mGluR5) as well as intracellular proteins of interest regarding signalling pathway (Stargazin, CaMKII).
A literature review was conducted to determine if these receptors migrated under particular pathological conditions or as the effect of drug treatment. NR1/NR2B Models of receptors were developed, compared to literature, validated and implemented in the glutamatergic synapse following specific characteristics.
Future goals include the definition of the remaining glutamate receptors of interest. The computational environment will be determined by characteristics observed by the cameras built by Photon etc and the focus will be extended on dendritic branches on which 10-15 excitatory synapses will be plugged into.
2. Multi-labeling of receptors in neurons (Paul De Koninck lab)
Specific labelling of two types of synaptic receptors, AMPA and NMDA, with different antibody-quantum dot combinations and labelling of post-synaptic sites on living neurons was achieved (see figure 2)