The Indirect Projection From The Vestibular Nucleus To The Area Of Nausea And Vomiting In The Rat Brainstem

The vestibular system comprises vestibular receptor,vestibular nerve,vestibular nuclei and relevant afferent and efferent pathways. Vestibular receptor includes otoliths organs which receive gravity and liner accelerative stimulation, and crista ampullaris which receive the information of the angle accelerative movement. The vestibular nuclei is the located site of the second neurons receiving the vestibular primary afferents, and integrates the information from the vestibular organ and other afferents, and regulates the body motions through the efferent projections. Variable motion, change of gravity and posture or head position could excite vestibular receptor, and then the vestibular system could modulate body posture, eye-movement, muscle strain so as to maintain the body balance, at the same time, it could rapidly modulate the circulation, respiration and other visceral activity for keeping the stabilization of internal environment. At present, it is believed that the motion sickness happened in riding, navigation or aviation is mostly induced by the abnormal activity of vestibular system. Therefore, it has become one of the focuses that the mechanism of the vestibular system in modulating the visceral activity, especially the mechanism of nausea and vomiting produced by visceral discomfort. The illumination of the mechanism has important academic and practical significance which to prevent and treat motion sickness, and to develop anti-motion sickness medicament.The vestibular signal that induced motion sickness certainly effect vomitting center, then produce nausea and vomiting. Therefore, the study of projection from vestibular nuclei to DVC has important academic and practical significance, which can illuminate the neuromechanism of nausea and vomiting caused by irregular signals from vestibular system.Emetic area is the name of all the brainstem nucleus which control vomiting. It lies in the brainstem from the obex to the caudal part of facial nucleus,it mainly contains area postrema(AP), nucleus tractus solitarius(NTS), dorsal nucleus of vagal nerve(DMV). AP,NTS and DMV are considered as a function unit, which is called dorsal vagal complex (DVC). Nowadays, DVC is regarded as the main area where the motion sickness and chemistry emetic act on, then induce vomiting and nausea.The pathway through which the vestibular signals induce nausea and vomitting is still remain unknown now. Some people believed that the projection from MVe and SpVe to NTS and DMV is the pathway through which the vestibular afferent induce nause and vomiting. However, from the review of the study of the pathway of vestibular afferent acts on respiration and visceral activity, the pathway from vestibular nucleus to NTS and DMV is treated as a secondry pathway. B J Yates believed that the possible pathway via which the vestibular signals induce vomiting is:vestibular nucleus→NTS→dorsal and ventral respiration groups→respiration movement neurons.In 1977, Porter etc. injected tetramethylrhodamine dextran in caudal vestibular nucleus in rat, and found there was direct projection from vestibular nucleus to DVC, they presumed that the direct projection played an important role in vestibule-viscus modulation. However Takeda etc. believed that there were two neural pathways from vestibular nucleus to DVC. They were as follows: first, vestibular nucleus→ventral laterl medulla→LC, which causes the motion sickness symptom of dim,disturbance of consciousness,lethargy and so on, because the activity of LC is restrained,leading to the waken of the norepinephrinergic system activity. Second, vestibular nucleus→ventral tegmental nucleus→hippocampus→tuberomammillary nucleus→DVC, it is the pathway of the irregular activity of autonomic nervous system and endocrine system, nause and vomiting when motion sickness occurs. But the hypothetic indirect pathway was based on some dispersive data and has not sequential morphological studies on the level of optical microscope or electron microscope. Some data indicated that there was the direct projection from vestibular nucleus to VLM, LPGi, Amb, PBN and so on, which could modulate the visceral activity.Because the rat has not vomiting activity, if it is used as experimental animal to study motion sickness, in the rat nerve system, we must indicate whether there is similar vomiting centre with emetic animal. The previously study in our laboratory, we Administered emetic drugs---cisplatin by intraperitoneal injection or stimulated vestibule by offer vertical axis rotation (OVAR) to observe the distribution of the Fos positive neurons in brains and compare the similarities and differences with the response of emetic animal in vomiting centre for revealing the possible location of vomiting centre in the rat. The result showed that emetic drug could induce visceral discomfort and there was similar emetic area with the emetic animal in rat's central nerve system. The visceral response induced by OVAR was similar with the visceral response induced by emetic drug in the sensation of nausea and vomiting. And the OVAR could effect the neuron associated with vomiting activity. The rat can be used as the experimental animal researching the nausea and vomiting mechanism of motion sickness. So based on the result of our previously study, the following experiments were processed by using anterograde tracing combined with retrograde tracing technique, immunohistochemical technique to study the direct or indirect pathway from vestibular nuclei to emetic center--DVC in Sprague-Dawley rat, to reveal the neural pathway of vestibular signal to vomiting centre, and offer the morphologic data for researching the mechanism of motion sickness in future.The results were as follows:1. The direct projection from vestibular nucleus to DPGi,Gi and PCRt After BDA was injected in MVe and SpVe respectively, the BDA-labeled fibers and terminals were found in extensive area of the pontine and the medulla. The patterns of projections were that SpVe and MVe have large projections to DPGi, PCRt, PrH, IOC, DTg and have the less projections to IRt, ECu, LC and caudal LPB, the projections in above area showed an ipsilateral predominance, and the two subnucleus have abundance contralateral projections to the Gi, GiA, GiV, the caudal Amb, Sp5DM and have the less projections to LPGi and VLM. The facts were approved by the results that the summarize of above anterograde and reterograde tracing experiments. The results are as following. (1) the SpVe had more projections to DPGi, PCRt, Gi, GiA, GiV of the MVe as a whole. (2) the rostral part of MVe had more projections to Gi, GiA, GiV than the middle and the caudal parts of MVe. (3) the caudal part of SpVe had more projections to Gi, GiA, GiV than the rostral part. (4) the SpVe and MVe had direct projections to DPGi, PCRt,Gi, there is not indirect pathway between the SpVe, MVe and the DPGi, PCRt,Gi. (5) There is few projections from MVe ,SpVe to NTS, DMV, AP, no buttons , so there no direct projections from VN to DVC.2. The direct projection from DPGi,Gi and PCRt to DVCAfter BDA was injected in DPGi,Gi and PCRt respectively, many BDA-labeled fibers and terminals were found in DVC, so we presumed and believe that there is a direct pathway from DPGi,Gi and PCRt to DVC. The detail results are as follows: After BDA was injected in DPGi, many BDA-labeled fibers and terminals were found in the dorsal part of NTS, DMV, AP, LPGi,PCRt, Irt, Gi, IOA, PrH, LC, PBN; there were sparse fibers and terminals were found in Amb,Cu and Sp5. The BDA-labeled fibers and terminals in above areas distributed bilaterally, all the subnucleus showed ipsilateral predominance except the PrH which showed contralateral.After BDA was injected in Gi, the distribution of BDA-labeled fibers and terminals were very similar to that of the injection of DPGi, the differences were:(1)there were more fibers and terminals distributed in laterl nucleus of NTS;(2)fewer fibers and terminals in AP;(3)sparse or no distribution in IO;(4)more in the caudal Sp5I,showed contralateral predominance;(5)there were also many fibers and terminals in DPGi, PCRt,showed ipsilateral predominance.After BDA was injected in PCRt,the distribution of BDA-labeled fibers and terminals were as follows:(1)many BDA-labeled fibers and terminals distributed in SolL,DMV, 12, PrH,showed contralateral predominance;(2)there were also many fibers and terminals distributed in IRt,LRt,Gi,DPGi, which showed ipsilateral predominance;(3)there were many in bilateral Sp5;(4)在the vestibular nucleus were distributed sparsely,showed contralateral predominance2. The indirect projection from vestibular nucleus to DVCAfter BDA was injected in MVe or SpVe and FG was injected in DVC in the same rat, the overlap areas of the PHA-L-labeled fibers and terminals and FG-labeled neurons were only found in DPGi,Gi and PCRt.The aforementioned results indicated that there was no direct pathway from MVe and SpVe to DVC, the pathway from MVe and SpVe to DVC is indirect, which is relayed by DPGi,Gi and PCRt. The possible pathway of vestibule---visceral response was as follows:The results provided morphological foundation for elucidating the neuro-mechanism of the vestibule-viscus modulation and vomiting produce in future.