Trigemino-autonomic connections in the muskrat: the neural substrate for the diving response

Stimulation of the anterior ethmoidal nerve of the muskrat produces a cardi orespiratory depression similar to the diving response. This includes an ap nea, a parasympathetic bradycardia, and a selective increase in sympathetic vascular tone. However, the brainstem circuitry that links the afferent st imulus to the efferent autonomic responses is unknown. We used the anterogr ade transneuronal transport of the herpes simplex virus (HSV-I), strain 129 , after its injection into the anterior ethmoidal nerve to determine the pr imary, secondary, and tertiary brainstem relays responsible for this cardio respiratory response. In an effort to check the validity of this relatively untested tracer, we also injected the medullary dorsal horn with biotinyla ted dextran amine to determine the secondary trigemino-autonomic projection s. Approximately 1 mu l (6X10(6) PFU) of the HSV-1 virus was injected direc tly into the anterior ethmoidal nerve of muskrats. After 2-6 days, their tr igeminal ganglions, spinal cords and brainstems were cut and immunohistolog ically processed for HSV-I. Initially (2 days), HSV-1 was observed only in the trigeminal ganglion. After approximately 3 days, HSV-1 was observed fir st in many brainstem areas optimally labeled between 4 and 4.5 days. In the se cases, the ventrolateral superficial medullary dorsal hem, the ventral p aratrigeminal nucleus and the interface between the interpolar and caudal s ubnuclei were labeled ipsilaterally. The nucleus tractus solitarius (NTS), especially its ventrolateral, dorsolateral, and commissural subnuclei were labeled as well as the caudal, intermediate and rostral ventrolateral medul la. Within the pens, the superior salivatory nucleus, the A5 area, the vent rolateral part of the parabrachial nucleus and the Kolliker-Fuse nucleus we re labeled. Only after a survival of 4 days or more, the locus coeruleus, t he nucleus raphe magnus, the nucleus paragigantocellularis, pars alpha, and the pontine raphe nucleus were labeled. Injections of biotinylated dextran amine were made into the medullary dorsal horn (MDH) in a location similar to that labeled after the viral injections. Fine fibers and terminals were labeled in the same brainstem areas labeled after injections of HSV-1 into the anterior ethmoidal nerve. This study outlines the potential brainstem circuit for the diving response, the most powerful autonomic reflex known. It also confirms the efficacy for using HSV-1, strain 129, as an anterograd e transneuronal transport method. (C) 2000 Elsevier Science B.V. All rights reserved.