The Direct Projections From The Vestibular Nucleus To The Visceral Regulatory Areas In The Brain Of Rat

The vestibular system is a highly conservative sensory system of the vertebrate, contributing to maintaining posture, computing spatial orientation, regulating muscular tone, adjusting eye-movement, modulating the autonomic function, and perceiving self-motion. The vestibular system is composed of vestibular organs, vestibular receptors, vestibular nerve, vestibular nucleus and the relative projection pathway. The vestibular receptors was excited by altereing velocity of motion, gravity change and the variety of posture or head position, and deliver the information to the areas in the brain that correlate with modulating the body posture, eye-movement, muscle strain so as to maintain the body balance, and as the same time, the information can modulate the circulation, alimentary function, respiration and other visceral activity rapidly, which could keep the stabilization of internal environment.Up to now, it is considered that the motion sickness is mostly induced by the abnormal activity of vestibular system, accompanying with riding, navigation or aviation. It is considered that the vestibular signals and the integration of the information from multitudinous receptors show an important role during motion sickness. Thus, to explain the mechanism of the vestibular system in modulating the visceral activity, especially the mechanism of nausea and vomiting produced by visceral discomfort is becoming more and more important to develop anti-motion sickness medicament, which has great academic and practical significance to prevent and treat motion sickness.The previously study in our laboratory has illustrated the direct projections from VN to VLR,LPGi,DPGi,Gi,PCRt,Amb,PBN in detail, which contral visceral reflex in brainstem. Regarding to the role of the reticular formation which integrating body-movement and viscera-movement, the author considered that the direct projections from VN to the reticular formation and the other visceral regulatory areas have an important role in triggering motion sickness. However, the proof of functional neuroanatomy is not enough.In previous study, neuroscientists payed more attention to the relationship between the VN and the nucleus of autonomic regulation in brainstem, but less attention to the relationship between the VN and the hypothalamus. It was reported that the hypothalamus produces a distinct modulating effect on the vestibular (rotatory and post-rotatory) nystagmus and labyrinthine posture-tonic reflexes. The hypothalamus can receive and integrate vestibular afferents according to the intensity of vestibular stimulation, and participate in vestibulo-autonomic reflexes. It remains unknown whether there are direct projections from VN to the hypothalamus.Evidence suggests that the lateral mammillary nucleus (LM) may play an important role in generating the head direction (HD) signal. Recently, Yates reported that vestibular information that contributes to the LM HD cell activity was relayed by the dorsal tegmental nucleus (DTg) and nucleus prepositus hypoglossi (PrH). Whereas, Canteras reported that the supragenual nucleus was a relay station for ascending vestibular signs to head direction cells. There was no evidence to identify the direct projection from VN to LM.Based on those results, in the present studys the following experiments were processed by using anterograde and retrograde tracing technique, combined with immunohistochemical technique in Wistar rat. (1) Whether can the VN neurons express FOS that projected to reticular formation nucleus by vestibular stimulation. (2) Whether were there the overlap relationship between the FOS-like neurons in the nucleus of the brainstem which regulate viscera active after administering emetic drugs---cisplatin by intraperitoneal injection and the projection fibers and terminals from VN? (3) Making sure that whether were there the direct pathway from vestibular nuclei to the hypothalamus. (4) Whether were there the direct pathway from VN to LM. The results were as follows:1. Following the retrograde tracer-FG was injected into DPGi or Gi and the vestibular organs was stimulated by OVAR, the double labeling neurons (FOS/FG) were found principally in bilateral MVe,SpVe,VLR,LPGi and LRt. The result showed that DPGi and Gi can accept vestibular signals and VN-DPGi and VN-Gi neural pathways might be involved in vestibulo-autonomic reflexes during vestibular stimulation.2. After anterograde tracer FITC-dextran was injected into VN and emetic drugs-cisplatin was administered by intraperitoneal injection, and the TH-like neurons was visioned by the immunohistochemistry or immunofluorescence, the overlap of the anterogradely labelled fibers and FOS-like neurons were found in the VLR,LRt and the transition zone between Sp5I and VLR, contralaterally preponderance. The overlap of the anterogradely labelled fibers and TH-like neurons were observed in A3,PF,VLR,LPGi,Gi and Giα. The overlap of the anterogradely labelled fibers and TH-like neurons and FOS-like neurons were found in SolM,LPGi,VLR and LC. The results suggest that VLR may be the important center to integrate vestibular information and viscera information because of its receiving both vestibular signals and unnormal viscera signals. A3,PF,VLR,LPGi,Gi and Giαmight participate directly in cardiovascular and respiratory regulation during vestibular stimulation.3. Following FITC-dextran was injected into the MVe, the anterogradely labeled fibers and terminals were observed in bilaterally PeF, the transition zone between PH and LH,ZI,and LH, with a contralateral predominance. Dense terminations were observed in LM, with an ipsilateral predominance. The FG-retrograde labeled neurons were found in MVe,SpVe and X , predominantly contralateral, after injection of FG into PeF. The result confirmed that the VN had direct projections to the PeF.4,After FITC-dextran was injected into the MVe, the anterogradely labeled fibers and terminals were the same as describing above. Especially anterogradely labelled fibers were seen predominantly ipsilaterally to LM. Following injections of retrograde tracers (FG) into LM, the FG-retrograde labeled neurons were found in ipsilateral MVe,SpVe,X,LVe,DTg,CGα,LDTg,Barrington and Giα. These results indicate that MVe had the direct projections into the LM.Our results provided morphological groundwork for illustrating the mechanism of vestibular -body reflection and vestibular - visceral reflex and vomiting produce in future .