Acupuncture has remarkable effects on treating functional gastrointestinal diseases, but its central mechanism is not clear. At present, the research has mainly focused on several central nuclei, such as the dorsal vagus complex (DVC), nucleus raphe magnus (NRM), locus coeruleus (LC), subnucleus reticularis dorsalis (SRD), hypothalamic paraventricular nucleus (PVN), cerebellar fastigial nucleus (FN), central amygdala (CeA), etc. It is not clear whether the nuclei are involved in acupuncture regulation of gastric function through certain interrelation. A further summary of related literature indicates that many brain regions or nuclei in the central nervous system are closely related to gastric function, such as DVC, NRM, parabrachial nuclei (PBN), LC, periaqueductal gray (PAG), cerebellum, PVN, arcuate nucleus (Arc), hippocampus, CeA, etc. Most of these nuclei have certain fiber connections with each other, in which DVC is the basic center, and other nuclei are directly or indirectly involved in the regulation of gastric function through DVC. Is DVC the key target in acupuncture regulation of gastric function? Does other nuclei have direct or indirect neural circuit with DVC to participate in the regulation of gastric function by acupuncture, such as the possibility of CeA-DVC neural loop in acupuncture regulating gastric function. Therefore, more advanced techniques such as photogenetics, chemical genetics should be introduced and the central mechanism of acupuncture on regulating gastric function with DVC as center, from the view of nerve loop, will become the focus of further research, which could explain the central integration mechanism of acupoint compatibility by modern neuroscience technology.
Acupuncture Therapy ; Locus Coeruleus ; Paraventricular Hypothalamic Nucleus ; Vagus Nerve

To clarify neuronal connection of the medial rectus muscle at brain stem, Bartha strain of the psecudorabies virus(PRV-Ba) and cholera toxin-horeserdish peroxidase(CT-HRP) was injected into medial rectus muscle of the rat. About 84 hours after PRV or CT-HRP injection, the brain was removed and processed immunohistochemical stain for PRV-Ba and neurohistochemical stain for CT-HRP using tetramethyl benzidine. The CT-HRP positive reaction was only present in ipsilateral oculomotor nucleus, contralateral abducence nucleus and bilaterally in rostral interstitial nucleus of medial longitudinal fasciculus, olivary pretectal nucleus, medial and superior vestibular nucleus, nucleus prepositus hypoglossi, prerubral field, nucleus Darkschewitsch, lateral substantia nigra, terminal nucleus of accessory nucleus, dorsal raphenucleus, locus ceruleus and pontime reticular formation. This study confirmed that both oculomotor nucleus and abducence nucleus were connected with each other through the medial longitudinal fasciculus, and neuronal connection of the medial rectus muscle in the rat brain stem.
Animals ; Brain Stem* ; Brain* ; Cholera ; Locus Coeruleus ; Neurons ; Rats* ; Reticular Formation ; Substantia Nigra

Although the distribution of locus ceruleus terminals has been demonstrated in the fundus striati[nucleus accumbens septi] by light microscopy[Jones & Moore, 1977 ; Mason & Fibiger, 1979 ; Streit or et al., 1979 ; Groenewegen et al., 1980], the synaptic organization of its terminals was not clarified. The purpose of the present investigation was to demonstrate the direct monosynaptic connection of the locus ceruleus terminals to the neuronal elements of the fundus stirati, and to clarify the synaptic structures of its terminals by electron microscopy two days after unilateral electric coagulation of the locus ceruleus. In the ipsilateral fundus striati, many axon terminals undergone dark degeneration were observed. These degenerating terminals containing small clear vesicles have asymmetric synaptic contacts with dendritic spines. Already two days after locus ceruleus lesion, distinct features of terminal degenerations appeared in the fundus striati ; enlarged axon terminals with altered synaptic vesicles, decrease of synaptic vesicles detached from the synaptic site, multiplication of dense bodies and infiltration of floccular material. At the same time, a regressive change occurred in which astrocytic processes encircled totally degenerated synapses spiraled around the synaptic remnants. These observations indicate that monosynaptic noradrenertic afferent connections to the fungus striati are confirmed, and the locus ceruleus terminals characterized by small round vesicles might be formed asymmetrical axo-spinous synapses with spiny neurons in the fundus striati.
Animals ; Cats* ; Dendritic Spines ; Fungi ; Locus Coeruleus* ; Microscopy, Electron ; Neurons ; Presynaptic Terminals ; Synapses ; Synaptic Vesicles

OBJECTIVETo study possible mechanisms of Shangjuxu (ST37) and the large intestine.

METHODSTotally 40 SD rats were selected. The distension of end colon was used as injured afferent stimulus. Activities of locus coeruleus (LC) neurons were recorded by extracellular microelectrode technique. Shangjuxu (ST37) and Hegu (L14) were needled to observe general features of discharge reactions, distention of colon induced discharge reactions of LC, and its effects on distention of colon induced discharge reactions of LC.

RESULTSDistention of colon could induce incrased discharge of LC neurons by 127.33% ± 45.48%. But needling at Shangjuxu (ST37) and Hegu (L14) could inhibit this injured response by 38.24% ± 7.69% and 21.29% ± 13.16% respectively (all P < 0.01).

CONCLUSIONSNeedling at Shangjuxu (ST37) and afferent signals of colon distension converged and interacted with each other. Needling at Shangjuxu (ST37) could significantly inhibit colon distension induced discharge of LC neurons, which might be one of mechanisms for Shangjuxu (ST37) and the large intestine relationship.

Acupuncture Therapy ; Animals ; Colon ; Intestine, Large ; Locus Coeruleus ; physiology ; Neurons ; Rats ; Rats, Sprague-Dawley

BACKGROUND AND OBJECTIVES: The precise mechanism of salicylic acid induced tinnitus has not been clearly identified as yet in spite of wide range of studies undertaken. We looked for the electrophysiologic evidence that salicylic acid has effect on the Locus Coeruleus (LC) neurons in vitro. MATERIALS AND METHOD: In LC, we measured the neuronal firing rate and cell membrane property according to the concentration of salicylic acid with extracellular single unit recording and whole cell current clamp recording. RESULTS: The basal firing activity was increased in 15 of the 20 LC nuclei, which were treated with 0.3 mM salicylic acid. Both 1mM and 2 mM salicylic acid increased the basal firing rate of all except for one LC neuron (n=20). These neurons also showed recovery after washing. However, 5 mM salicylic acid induced cell death after the bursting response in all of the LC neurons (n=10)(Fig. 2). There were no specific changes in the whole cell current-clamp recording of the LC neurons during the period of drug treatment (Fig. 3). CONCLUSION: The dose dependent response pattern observed in the extracellular single unit recording and the fact that there were no specific changes in the whole-cell current-clamp recording following the salicylic acid treatment suggest that the salicylic acid induced intracellular change in the LC neuron is caused not by the direct ligand-receptor reaction but by the indirect 2nd messenger system.
Animals ; Cell Death ; Cell Membrane ; Fires ; Locus Coeruleus ; Neurons ; Patch-Clamp Techniques ; Rats* ; Salicylic Acid* ; Tinnitus

The effect of MPTP on catecholamine neurons in young (4-6 weeks) and aging (10-12 months) C57BL/6 mice was studied using immunocytochemical techniques. Both groups of mice received 4 repeated dosages of 10mg/kg of MPTP given 12 hours apart. We compared the number of tyrosine hydroxylase (TH)-positive cell bodies using immunocytochemical technique in substantia nigra (SN), ventral tegmental area(VTA) and locus ceruleus (LC) 7 days after the last injection of MPTP. There was a significant decrease in the number of TH-positive cell bodies in the SN of young mice, but not in VTA or LC. In aging mice, there was a significant decrease in the number of TH-positive cell bodies in VTA as well as in SN. It is concluded that aging mice are more sensitive to MPTP and show more widespread damage in the catecholamine neurons than young mice, suggesting that MPTP-treated aging mice provide a more useful model for studing anatomical characteristics of Parkinson's disease than young mice.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine* ; Aging* ; Animals ; Brain* ; Locus Coeruleus ; Mice* ; Neurons ; Parkinson Disease ; Substantia Nigra ; Tyrosine 3-Monooxygenase

AIMTo investigate the effects of alpha1 and alpha2 receptors in the locus ceruleus (LC) on carotid baroreflex (CBR) resetting induced by intracerebroventricular injection (ICV) of histamine (HA).

METHODSThe left and right carotid sinus regions were isolated from the systemic circulation in 23 Sprague-Dawley rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure (ISP) was altered in a stepwise manner. ISP-mean arterial pressure (MAP) relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. The changes in CBR performance induced by ICV HA and the effects of pretreatment with alpha1 or alpha2 receptor antagonist into the LC on the responses of CBR to HA were examined.

RESULTSICV HA (60 micromol x L(-1) in 5 microl) significantly shifted the ISP-MAP relationship curve upwards (P < 0.05) and reduced the MAP range and maximum gain (P < 0.05). The pretreatment with phenoxybenzamine (PBZ, a selective antagonist of alpha1 receptor, 3 micromol x L(-1) in 500 nl) or yohimbine (YOH, a selective antagonist of alpha2 receptor, 2.5 micromol x L(-1) in 500 nl) into the LC could obviously intensify the above-mentioned changes in CBR performance induced by HA, but the intensive effect of PBZ was less remarkable than that of YOH (P < 0.05).

CONCLUSIONThe intracerebroventricular administration of HA results in a rapid resetting of CBR and a decrease in reflex sensitivity, and the functions of alpha1 and alpha2 receptors in the LC may attenuate CBR resetting induced by ICV HA. Furthermore, alpha2 receptor in the LC might play a more important role in regulating the responses of CBR to HA.

Animals ; Baroreflex ; drug effects ; physiology ; Carotid Sinus ; Histamine ; pharmacology ; Locus Coeruleus ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Neurotransmitter

This study was carried out to investigate the morphology, distribution and co-localization of calbindin D-28k and parvalbumin-containing GABAergic cells in the midbrain of the cat. The results obtain by immunocytochemical observation were as follows : 1. Calcium binding protein calbindin D-28k and parvalbumin immunoreactive neurons were mainly found in the red nucleus, substantia nigra, oculomotor nucleus and locus ceruleus of the cat midbrain. 2. Parvalbumin immunoreactive cells in the red nucleus were more than twice in number compared to the calbindin D-28k immunoreactive cells. 3. Calbindin immunoreactive cells in the substans nigr were more than twice in number compared to the parvalbumin immunoreactive cells. 4. Double labelled immunocytochemical study revealed that parvalbumin and GABA were colocalized neurons in the same cells of the transverse section of the midbrain. 5. Calbindin D-28k and parvalbumin-immunoreactive cells were round, oval, spindle or polygonal in shape and were 15~20 micrometer in diameter. Positive neurons displayed unipolar, bipolar, or multipolar feature.
Animals ; Calbindins* ; Calcium ; Carrier Proteins ; Cats* ; GABAergic Neurons* ; gamma-Aminobutyric Acid ; Immunohistochemistry ; Locus Coeruleus ; Mesencephalon* ; Neurons ; Red Nucleus ; Substantia Nigra

BACKGROUND AND OBJECTIVES: Subjective tinnitus, a distracting internal noise, is experienced by humans. Tinnitus is evoked by salicylic acid treatment in rats as confirmed by Jastreboff in 1994 in an animal behavior model of tinnitus with salicylic acid. The objective of this study is to evaluate c-fos expression in the brain stem of rats after salicylic acid treatment. MATERIALS AND METHOD: After salicylic acid (450 mg/kg) and saline treatment (450 mg/kg), c-fos immunohistochemical staining expression in the auditory and nonauditory brain stem nuclei were observed. RESULTS: Many immunoreactive cells were observed in the Locus Ceruleus of the salicylic acid treated animals, but not in the saline treated animals. No immunoreactive cells were found in the auditory brain stem nuclei. CONCLUSION: The Locus Ceruleus is the nucleus of the brain stem and produce norepinephrine which results in arousal of the neuronal activity for stress. These results suggest that salicylic acid may evoke tinnitus through a combined effect on the auditory and nonauditory brain nuclei. It seems possible that the interaction of these effects at particular locations of the brain causes tinnitus.
Animals ; Arousal ; Behavior, Animal ; Brain Stem* ; Brain* ; Humans ; Locus Coeruleus ; Neurons ; Noise ; Norepinephrine ; Rats* ; Salicylic Acid* ; Tinnitus

Mongolian gerbil (Meriones unguiculatus) has been as an model animal for studing the neurologic disease because of the long-term survival in the condition of water-deprived desert condition. In order to accomplish the this research, first of all another divided the laboratory animals 10groups. In this study of the long term water deprived condition investigated catecholamine synthetic enzymes, tyrosine hydroxylase(TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine-N- methyltransferase(PNMT) in the brain by using immunohistochemical stain. The results obtained in this study were summarized as following. 1. It were observed TH-IR cells in substantia nigra pars compacta, ventral tegmental area and substantia nigra pars reticular of Midbrian. Most of them were presented in pars compacta and ventral tegmental area, but a few in pars reticular. TH-IR cell decreased until the 5th water-deprived day, increased from the 10th water-deprived day to the 15th water-deprived day and redecreased in the 20th water-deprived day 2. In locus ceruleus and rubrospinal tract were observed TH-IR cells and a few DBH-IR cell. Therefore there was composed of dopaminergic neuron and noradrenergic neuron. 3. The quantity of dopamin in serum were decreased until the 4th water-deprived day, increased from the 5th water-deprived day, redecreased on the 15th water-deprived day and reincreased from the 20th water-deprived day.
Adrenergic Neurons ; Animals ; Animals, Laboratory ; Brain ; Dopaminergic Neurons ; Gerbillinae* ; Locus Coeruleus ; Mesencephalon* ; Pons* ; Substantia Nigra ; Tyrosine ; Ventral Tegmental Area