Firing clamp: a novel method for single-trial estimation of excitatory and inhibitory synaptic neuronal conductances.

Anton V Chizhov,Lyle J Graham,Evgenya Malinina,Michael Druzin,Staffan Johansson

doi:10.3389/fncel.2014.00086

Abstract

Understanding non-stationary neuronal activity as seen in vivo requires estimation of both excitatory and inhibitory synaptic conductances from a single trial of recording. For this purpose, we propose a new intracellular recording method, called “firing clamp.” Synaptic conductances are estimated from the characteristics of artificially evoked probe spikes, namely the spike amplitude and the mean subthreshold potential, which are sensitive to both excitatory and inhibitory synaptic input signals. The probe spikes, timed at a fixed rate, are evoked in the dynamic-clamp mode by injected meander-like current steps, with the step duration depending on neuronal membrane voltage. We test the method with perforated-patch recordings from isolated cells stimulated by external application or synaptic release of transmitter, and validate the method with simulations of a biophysically-detailed neuron model. The results are compared with the conductance estimates based on conventional current-clamp recordings.

Highlights

Understanding information processing in the brain requires knowledge of neuronal impulse activity and the corresponding synaptic conductance inputs onto target neurons
The synaptic conductances arising from these populations, which control the evolution of transmembrane voltage of the target neuron, may provide information on the excitatory and inhibitory neuronal population activities
To improve the single-trial estimation of synaptic activity, we propose a new quasi-dynamic clamp method that exploits the non-linear dynamics of the action potential

Summary

Introduction

Understanding information processing in the brain requires knowledge of neuronal impulse activity and the corresponding synaptic conductance inputs onto target neurons. Estimates of postsynaptic conductances can be obtained from intracellular recordings in a single neuron, but experimental methods of such estimations are still under development, with a principal difference between methods being whether they require repetitive recordings that assume identical input conditions, or not. Assuming only two types of synaptic input, excitatory and inhibitory, if the averaged traces of voltage or current are recorded at different levels of polarization, and the reversal potentials of both excitatory and inhibitory currents (VE and VI) are known, algebraic calculations provide estimates for the corresponding conductances, GE and GI. In a recent paper, Odom and Borisyuk (2012) generalized the current-clamp approach to the case of three estimated synaptic conductances with the help of multiplicative noise, but with the assumption that non-linear channels do not contribute to the recorded voltage traces and the variance of estimated conductance is known a priori

Methods

Results

Conclusion