Signal processing and modeling of voltage imaging in dendritic spines
collaboration with R. Yuste (Columbia)
Neurons are organized in local microdomains characterized by morphological and functional specificities. Distinct microdomains include dendritic spines and synapses, which play a major role in neuronal communication by mediating transmission of signals across the synaptic cleft. Synaptic transmission involves flow of ionic currents through surface receptors located on the post-synaptic terminal, and further activation of voltage- and gated ion channels. But How synaptic current modulates and regulates the local voltage remains difficult to study due to the lack of specific sensors and the theoretical hurdle of understanding the dynamics of charged particles in shaped geometrical domains.
We study electro-diffusion in cellular microdomains and in particular to address the role of the local geometry of microdomains such as the dendritic spines in modulating synaptic transmission and plasticity. This research combines modeling and simulations of electro-diffusion with multiscale imaging data to analyze the voltage-current relationship in neuronal micro-domains. Experimental imaging data are collected from genetically encoded voltage sensitive dyes in pyramidal neurons in cultures and slices and the model will be finally tested with ultrastructural reconstructions.
collaboration with E. Korkotian and M. Segal
Dendritic spines, the locus of excitatory synaptic interaction in central neurons constitutes a unique intracellular calcium compartment, in that it can raise Ca to levels higher than those of the parent dendrite. A transient rise of internal calcium can bring about a fast twitch of dendritic spines, the function of which is still unclear. We have proposed (19-20) an explanation of the cause and effect of the twitching and its role in the functioning of the spine as a fast calcium compartment. The dimension of a dendritic Spine is such that this structure is at an intermediate scale between the discreet and the continuum. Thus new approaches are needed to model processes occuring at this scale, such as the induction of synaptic plasticity, which underlies learning and memory.
Chemical reactions in microdomains
Traditional chemical kinetics may be inappropriate to describe chemical reactions in micro-domains involving only a small number of substrate and reactant molecules. Starting with the stochastic dynamics of the molecules, we have derived a master-diffusion equation for the joint probability density of a mobile reactant and the number of bound substrate in a confined domain. We used the equation to calculate the fluctuations in the number of bound substrate molecules as a function of initial reactant concentration. This model can be used for the description of noise due to gating of ionic channels by random binding and unbinding of ligands in biological sensor cells, such as olfactorycilia, photo-receptors, hair cells in the cochlea.