Determination of effective synaptic conductances using somatic voltage clamp

Songting Li, Nan Liu, Li Yao, Xiaohui Zhang, Doug Zhou, David Cai

    Research output: Contribution to journalArticle

    Abstract

    The interplay between excitatory and inhibitory neurons imparts rich functions of the brain. To understand the synaptic mechanisms underlying neuronal computations, a fundamental approach is to study the dynamics of excitatory and inhibitory synaptic inputs of each neuron. The traditional method of determining input conductance, which has been applied for decades, employs the synaptic current-voltage (I-V) relation obtained via voltage clamp. Due to the space clamp effect, the measured conductance is different from the local conductance on the dendrites. Therefore, the interpretation of the measured conductance remains to be clarified. Using theoretical analysis, electrophysiological experiments, and realistic neuron simulations, here we demonstrate that there does not exist a transform between the local conductance and the conductance measured by the traditional method, due to the neglect of a nonlinear interaction between the clamp current and the synaptic current in the traditional method. Consequently, the conductance determined by the traditional method may not correlate with the local conductance on the dendrites, and its value could be unphysically negative as observed in experiment. To circumvent the challenge of the space clamp effect and elucidate synaptic impact on neuronal information processing, we propose the concept of effective conductance which is proportional to the local conductance on the dendrite and reflects directly the functional influence of synaptic inputs on somatic membrane potential dynamics, and we further develop a framework to determine the effective conductance accurately. Our work suggests re-examination of previous studies involving conductance measurement and provides a reliable approach to assess synaptic influence on neuronal computation.

    Original languageEnglish (US)
    Pages (from-to)e1006871
    JournalPLoS computational biology
    Volume15
    Issue number3
    DOIs
    StatePublished - Mar 1 2019

    Fingerprint

    Clamping devices
    Conductance
    dendrites
    Dendrites
    Voltage
    Neurons
    neurons
    Electric potential
    information processing
    Dendrite
    methodology
    Automatic Data Processing
    membrane potential
    Membrane Potentials
    brain
    Neuron
    Brain
    transform
    experiment
    Experiments

    ASJC Scopus subject areas

    • Ecology, Evolution, Behavior and Systematics
    • Modeling and Simulation
    • Ecology
    • Molecular Biology
    • Genetics
    • Cellular and Molecular Neuroscience
    • Computational Theory and Mathematics

    Cite this

    Determination of effective synaptic conductances using somatic voltage clamp. / Li, Songting; Liu, Nan; Yao, Li; Zhang, Xiaohui; Zhou, Doug; Cai, David.

    In: PLoS computational biology, Vol. 15, No. 3, 01.03.2019, p. e1006871.

    Research output: Contribution to journalArticle

    Li, Songting ; Liu, Nan ; Yao, Li ; Zhang, Xiaohui ; Zhou, Doug ; Cai, David. / Determination of effective synaptic conductances using somatic voltage clamp. In: PLoS computational biology. 2019 ; Vol. 15, No. 3. pp. e1006871.
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