Voltage clamp analysis of nonlinear dendritic propertie in prepositus hypoglossi neurons

TL;DR

This study introduces QSA, a novel voltage clamp analysis method, to quantify dendritic nonlinearities in prepositus hypoglossi neurons, revealing key roles of sodium and NMDA conductances in neural integrator function.

Contribution

The paper presents QSA as a new compact approach to analyze nonlinear dendritic responses, simplifying complex biophysical models with eigendecomposition.

Findings

Nonlinear responses are dominated by dendritic properties.

Persistent sodium conductance is crucial for nonlinear effects.

Dendritic nonlinearities differ significantly between neuron types B and D.

Abstract

The nonlinear properties of the dendrites in prepositus hypoglossi neurons are involved in maintenance of eye position. The biophysical properties of these neurons are essential for the operation of the vestibular neural integrator that converts a head velocity signal to one that controls eye position. A novel method named QSA (quadratic sinusoidal analysis) for voltage clamped neurons was used to quantify nonlinear responses that are dominated by dendrites. The voltage clamp currents were measured at harmonic and interactive frequencies using specific stimulation frequencies, which act as frequency probes of the intrinsic nonlinear neuronal behavior. These responses to paired frequencies form a matrix that can be reduced by eigendecomposition to provide a very compact piecewise quadratic analysis at different membrane potentials that otherwise is usually described by complex differential equations involving a large numbers of parameters and dendritic compartments. Moreover, the QSA matrix can be interpolated to capture most of the nonlinear neuronal behavior like a Volterra kernel. The interpolated quadratic functions of the two major prepositus hypoglossi neurons, namely type B and D, are strikingly different. A major part of the nonlinear responses is due to the persistent sodium conductance, which appears to be essential for sustained nonlinear effects induced by NMDA activation and thus would be critical for the operation of the neural integrator. Finally, the dominance of the nonlinear responses by the dendrites supports the hypothesis that persistent sodium conductance channels and NMDA receptors act synergistically to dynamically control the influence of individual synaptic inputs on network behavior.