A novel theoretical framework for simultaneous measurement of excitatory and inhibitory conductances

PLoS Comput Biol. 2021 Dec 28;17(12):e1009725. doi: 10.1371/journal.pcbi.1009725. eCollection 2021 Dec.


The firing of neurons throughout the brain is determined by the precise relations between excitatory and inhibitory inputs, and disruption of their balance underlies many psychiatric diseases. Whether or not these inputs covary over time or between repeated stimuli remains unclear due to the lack of experimental methods for measuring both inputs simultaneously. We developed a new analytical framework for instantaneous and simultaneous measurements of both the excitatory and inhibitory neuronal inputs during a single trial under current clamp recording. This can be achieved by injecting a current composed of two high frequency sinusoidal components followed by analytical extraction of the conductances. We demonstrate the ability of this method to measure both inputs in a single trial under realistic recording constraints and from morphologically realistic CA1 pyramidal model cells. Future experimental implementation of our new method will facilitate the understanding of fundamental questions about the health and disease of the nervous system.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • CA1 Region, Hippocampal* / cytology
  • CA1 Region, Hippocampal* / physiology
  • Computational Biology
  • Electrophysiology
  • Mice
  • Models, Neurological*
  • Neurons* / cytology
  • Neurons* / physiology

Grants and funding

This work was supported by grants from the DFG-SFB 1089 (to HB and IL), 01EW1606 - DeCipher EraNet Neuron (to HB and IL), Israel Science Foundation (ISF 1539/17 and ISF Bikura 2799/20) (to IL), Minerva Foundation (to IL) and Human Frontier Science Program (HFSP) (to IL). IL is the incumbent of the Norman and Helen Asher Professorial Chair. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.