Abstract
Dendritic integration and neuronal firing patterns strongly depend on biophysical properties of synaptic ligand-gated channels. However, precise estimation of biophysical parameters of these channels in their intrinsic environment is complicated and still unresolved problem. Here we describe a novel method based on a maximum likelihood approach that allows to estimate not only the unitary current of synaptic receptor channels but also their multiple conductance levels, kinetic constants, the number of receptors bound with a neurotransmitter, and the peak open probability from experimentally feasible number of postsynaptic currents. The new method also improves the accuracy of evaluation of unitary current as compared to the peak-scaled non-stationary fluctuation analysis, leading to a possibility to precisely estimate this important parameter from a few postsynaptic currents recorded in steady-state conditions. Estimation of unitary current with this method is robust even if postsynaptic currents are generated by receptors having different kinetic parameters, the case when peak-scaled non-stationary fluctuation analysis is not applicable. Thus, with the new method, routinely recorded postsynaptic currents could be used to study the properties of synaptic receptors in their native biochemical environment.
Highlights
Intrinsic biophysical properties of synaptic receptor channels are important for determining of both efficacy of synaptic transmission and activation of dendritic voltage-gated channels underlying active properties of dendrites
In the newly developed method, maximum likelihood non-stationary fluctuation analysis (ML NSFA), the number of liganded receptors was first optimized for each macroscopic current and these estimates were used to maximize the log-likelihood in order to obtain a set of kinetic model parameters as it was described earlier (Stepanyuk et al, 2011)
We explored the performance of ML NSFA with several different kinetic schemes of varying complexity and varying conditions relevant for real synaptic transmission
Summary
Intrinsic biophysical properties of synaptic receptor channels are important for determining of both efficacy of synaptic transmission and activation of dendritic voltage-gated channels underlying active properties of dendrites. Changes in the postsynaptic receptor number, unitary conductance, and kinetics may affect dendritic integration (Magee, 2000) and lead to alteration in synaptic strength and memory function (Li and Tsien, 2009) in normal (Benke et al, 1998) and pathological states (Kittler et al, 2004). Postsynaptic receptors in their native environment are hardly accessible experimentally, and this limitation has rendered their biophysical properties notoriously difficult to study. It makes it almost impossible to directly apply receptor biophysical parameters obtained in a heterologous system to the analysis of postsynaptic receptors under physiological conditions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
