Computational investigation of Glutamate-AMPA interaction in synaptic transmission

The excitatory synaptic response, the base of all the brain activity, is the object of a huge amount of researches and fairly all the structural elements of this synapse are investigated to stress out how they contribute to shape the response. To this aim mathematical models and computer simulation are providing valuable information. A previous model of excitatory synapse, based on Brownian motion of Glutamate (GLUT) molecules within the synaptic cleft and their bind- ing to post-synaptic receptors [Ventriglia and Di Maio (2000), Ventriglia and Di Maio (2003), Ventriglia (2011)], was enhanced by upgrading some parameters to new values, produced by re- cent experimental findings [Armstrong and Gouaux (2000), Mainen et al. (2002), Santos et al. (2009), Tichelaar et al. (2004), 1]. Since in a previous paper, in which the binding to receptors was stud- ied via mEPSCs linked to AMPARs trafficking, demonstrated the possibility to define an inferior limit for the binding probability between the GLUT and receptor binding site, this fact was more thoroughly investigated by a longer series of computer simulations [Ventriglia and DiMaio (2012)]. Also, the new data, which define better the 3D structure (and dimensions) of AMPA recep- tors, allowed us to investigate the effects produced on the synaptic response of the change of the heigth of the part of AMPA receptors which protrudes in the cleft from the PSD zone [Tichelaar et al. (2004)]. Moreover, the decreasing of the response with the increasing of the excentricity of the position on AZ of the releasing vesicle has been demonstrated by using also the space distribution of number of collision of GLUT molecules on receptor binding sites. Also, the dynamics of the binding has been studied by means of the description of the inter-collision times among single Glut molecules and the binding sites of the several AMPA receptors which they visit without success till the final binding.