Dramatically amplified thoracic sympathetic postganglionic excitability and integrative capacity revealed with whole-cell patch clamp recordings.

Thoracic paravertebral sympathetic chain postganglionic neurons (tSPNs) comprise the final integrative output of the distributed sympathetic nervous system controlling vascular and thermoregulatory systems. Considered a non-integrating relay, what little is known of tSPN intrinsic excitability has been determined by sharp microelectrodes with presumed impalement injury. We thus undertook the first electrophysiological characterization of tSPN cellular properties using whole-cell recordings and coupled results with a conductance-based model to explore the principles governing their excitability in adult mice of both sexes.Recorded membrane resistance and time constant values were an order of magnitude greater than values previously obtained, leading to a demonstrable capacity for synaptic integration in driving recruitment. Variation in membrane resistivity was the primary determinant controlling cell excitability with vastly lower currents required for tSPN recruitment. Unlike previous microelectrode recordings in mouse which observed inability to sustain firing, all tSPNs were capable of repetitive firing. Computational modeling demonstrated that observed differences are explained by introduction of a microelectrode impalement injury conductance. Overall, tSPNs largely linearly encoded injected current magnitudes over a broad frequency range with distinct subpopulations differentiable based on repetitive firing signatures.Thus, whole-cell recordings reveal tSPNs have more dramatically amplified excitability than previously thought, with greater intrinsic capacity for synaptic integration and with the ability for maintained firing to support sustained actions on vasomotor tone and thermoregulatory function. Rather than acting as a relay, these studies support a more responsive role and possible intrinsic capacity for tSPNs to drive sympathetic autonomic function. Thoracic sympathetic postganglionic neurons (tSPNs) represent the final neural output for control of vasomotor and thermoregulatory function. We used whole-cell-recordings and computational modeling to provide broad insight on intrinsic cellular mechanisms controlling excitability and capacity for synaptic integration. Compared to past intracellular recordings using microelectrode impalement, we observed dramatically higher membrane resistivity with primacy in controlling enhanced tSPN excitability and recruitment via synaptic integration. Compared to reported phasic firing, all tSPNs fire repetitively and linearly encode injected current magnitude to firing frequency over a broad range. Modeling studies suggest microelectrode impalement injury accounts for differences in tSPN properties previously observed. Overall, intrinsic tSPN excitability plays a much greater role in the integration and maintenance of sympathetic output than previously thought.