Neural Substrates of Spinal Sensory Integration for Reflex Control of Sympathetic Outflow: Where’s the Connection?

Proper adaptation to external and internal stimuli demand changes in physiology that are coordinated with motor responses. Motor responses are achieved via local circuit connections in the spinal cord and require physiological adjustments in order to be executed. Previous studies provide evidence that segmental spinal interneurons coordinate this activity. However, the identity and synaptic organization of neurons contributing to this circuitry has not been fully characterized. We hypothesize that sensory input from primary sensory afferents is integrated by local circuits that enable adaptive adjustments in sympathetic outflow through polysynaptic projections to sympathetic preganglionic neurons (SPGs) in the thoracic spinal cord. We tested this hypothesis in two experiments employing viral transneuronal tracing. In the first, a recombinant strain of PRV, either PRV263 or PRV279, was injected into the rat kidney and retrograde transneuronal passage of the virus in thoracic cord was characterized. Immunocytochemical localization of viral antigens revealed a temporally organized progression of infection through SPGs into interneuron populations in Rexed laminae VII, V, IV, II and I. Retrograde transneuronal infection reproducibly identified subpopulations of neurons in each lamina and the temporal progression of infection was consistent with multiple parallel pathways from superficial lamina to SPGs. The second experiment utilized the expression of the farnesylated EYFP reporter that is expressed by PRV279. Localization of the farnesylated EYFP reporter defined the dendritic architecture of infected interneurons and also revealed patterns of axonal arborization coextensive with infected interneurons. Analysis of axons in both the longitudinal and transverse planes support the circuit identified in the first experiment. Both experiments reveal a segmental organization of interneurons with respect to regulation of SPG output and a neural network that appears to coordinate sympathetic outflow from multiple spinal cord segments