Calmodulin-calcium complexes kinetics as a source of nonlinearity for calcium dependent plasticity

Abstract

Event Abstract Back to Event Calmodulin-calcium complexes kinetics as a source of nonlinearity for calcium dependent plasticity Ruben Tikidji-Hamburyan1* and Alexandra Tikidji-Hamburyan1 1 Southern Federal University, Research Institute for Neurocybernetics, Russia Long-term depression (LTD) and potentiation (LTP), two forms of synaptic plasticity, are prominent phenomena of brain nerve tissue, and thought to be the cellular basis for the processes underlaying learning and memory [1, 2]. Experimental data obtained in last decade reveal that free calcium concentration in postsynaptic intracellular solution can trigger long-term plasticity [3]. According to "calcium control hypothesis" the low concentration of intracellular calcium [Ca2+] does not change synaptic conductivity, whereas middle and high concentrations induce LTD and LTP respectively. Such dependence requires the nonlinearity of sensitivity of synaptic modification to peak calcium concentration [4]. Modified versions of this hypothesis include calmodulin and calmodulin kinase II dynamics [1, 5, 6], allosteric kinetics [7] or IQ-motif proteins influence [8] to account for the differential induction of LTD and LTP and the nonlinearity of sensitivity curve. However, the calcium ions penetrated into the cell are mostly bound by calmodulin (CaM), a small (16.8 kDa) ubiquitous Ca2+ binding protein. CaM molecule can bind up to four calcium ions by two sites in both C-lobe and N-lobe [6, 8]. Stopped flow fluorescence studies [9, 10] showed that these two sites are quasi independent and have different association/dissociation reaction constants [6, 8]. Preliminary study of the minimalistic model of chemical kinetics of eight calmodulin - calcium complexes showed that all complexes may be split into five groups according to the maximal concentration moment and time constant of concentration decay: (i) early-fast, (ii) early-middle, (iii) belated-fast, (iv) belated-middle, and (v) farther-slow groups. In this study I used these preliminary results for reconstruction of the dependency curve of synaptic weight from the free calcium concentration [4]. In the second order model, the two hypothetical LTP and LTD agents were included and the dynamical system for synaptic weight was constructed. I assumed that the LTD agent is activated by the calmodulin complexes from early-middle and belated-middle groups whereas the LTP one is activated by the farther-slow and belated-fast groups' members. The resulting curve of the value of synaptic weight in the steady state from the peak of the free calcium concentration is shown on the Fig.1. The variation of initial calmodulin concentration shifted this curve and it's LTP or LTD part may be eliminated. INCF-09-2131