IDENTIFICATION OF RENAL SYMPATHETIC PREGANGLIONIC NEURONS IN HAMSTERSUSING TRANSSYNAPTIC TRANSPORT OF HERPES-SIMPLEX TYPE-1 VIRUS

Herpes viruses have been used as retrograde transsynaptic tracers to i dentify pathways from the CNS to specific target tissues. We used herp es simplex virus to identify central nervous system neurons responsibl e for control of the kidney. Herpes simplex type 1 or herpes simplex t ype 2 was injected into rat kidneys and herpes simplex type 1 was micr oinjected into hamster and guinea pig kidneys. After three to seven da ys, ganglia, spinal cords and brains were examined using immunohistoch emistry to visualize the virus-infected neurons. Our first experiments demonstrated that rats were not susceptible to infection with neurotr opic strains of herpes simplex type 1. Injections of a wildtype strain of herpes simplex type 2 into rat kidneys led to nonspecific infectio n of many central nervous system neurons and glia. In contrast, herpes simplex type 1 injections in hamsters and guinea pigs caused specific infection of limited numbers of neurons in approximately one-third of the animals and the study was continued using hamsters. Sympathetic p reganglionic neuron labelling was found in the ipsilateral intermediol ateral cell column of the spinal cord as well as the lateral funiculus . Most infected preganglionic neurons were located in the seventh to t he ninth thoracic spinal segments. Infected neurons were not found in the dorsal or ventral horn of the spinal gray matter and only one or t wo cells were found in the brainstem. Sympathetic preganglionic neuron morphology was usually normal, showing detailed dendritic arborizatio ns, and lysis was infrequent. Small infected cells were sometimes obse rved close to sympathetic preganglionic neurons. Because herpes simple x type 1 virus was not detected immunocytochemically in ganglionic neu rons in these same hamsters, the polymerase chain reaction was used in some additional hamsters to detect viral DNA in the T12 and T13 chain ganglia and splanchnic ganglia ipsilateral to the kidney injected wit h herpes simplex type 1. Finally, the overall distribution of renal po stganglionic and splanchnic preganglionic neurons in hamsters was exam ined for comparison to the number and locations of virus-labelled neur ons. Retrograde transport of the fluorescent dye FluoroGold demonstrat ed that (i) renal postganglionic neurons are distributed in the T10-L1 chain ganglia and in the prevertebral splanchnic ganglion and (ii) sp lanchnic preganglionic neurons are located in the T3-T12 spinal segmen ts, predominantly in the intermediolateral and funicular spinal autono mic nuclei. In conclusion, herpes simplex type 1 virus infected an exc lusive population of ''renal'' neurons in hamsters without lysis and w ith little cellular reaction to the infection after a survival period of three days, permitting these neurons to be studied in detail.