Nonreflecting Boundary Conditions for a CSF Model of Fourth Ventricle: Spinal SAS Dynamics.

In this paper, we introduce a one-dimensional model for analyzing the cerebrospinal fluid dynamics within the fourth ventricle and the spinal subarachnoid space (SSAS). The model has been derived starting from an original model of Linninger et al. and from the detailed mathematical analysis of two different reformulations. We show the steps of the modelization and the rigorous analysis of the first-order nonlinear hyperbolic system of equations which rules the new CSF model, whose conservative-law form and characteristic form are required for the boundary conditions treatment. By assuming sub-critical flows, for the particular dynamics we are dealing with, the most desirable option is to employ the nonreflecting boundary conditions, that allow the simple wave associated with the outgoing characteristic to exit the computational domain with no reflections. Finally, we carry out some numerical simulations related to different cerebral physiological conditions.

Caudal fourth ventricular administration of the AMPK activator 5-aminoimidazole-4-carboxamide-riboside regulates glucose and counterregulatory hormone profiles, dorsal vagal complex metabolosensory neuron function, and hypothalamic Fos expression.

This study investigated the hypothesis that estrogen controls hindbrain AMP-activated protein kinase (AMPK) activity and regulation of blood glucose, counterregulatory hormone secretion, and hypothalamic nerve cell transcriptional status. Dorsal vagal complex A2 noradrenergic neurons were laser microdissected from estradiol benzoate (E)- or oil (O)-implanted ovariectomized female rats after caudal fourth ventricular (CV4) delivery of the AMPK activator 5-aminoimidazole-4-carboxamide-riboside (AICAR), for Western blot analysis. E advanced AICAR-induced increases in A2 phospho-AMPK (pAMPK) expression and in blood glucose levels and was required for augmentation of Fos, estrogen receptor-α (ERα), monocarboxylate transporter-2, and glucose transporter-3 protein in A2 neurons and enhancement of corticosterone secretion by this treatment paradigm. CV4 AICAR also resulted in site-specific modifications in Fos immunolabeling of hypothalamic metabolic structures, including the paraventricular, ventromedial, and arcuate nuclei. The current studies demonstrate that estrogen regulates AMPK activation in caudal hindbrain A2 noradrenergic neurons during pharmacological replication of energy shortage in this area of the brain, and that this sensor is involved in neural regulation of glucostasis, in part, through control of corticosterone secretion. The data provide unique evidence that A2 neurons express both ERα and -ß proteins and that AMPK upregulates cellular sensitivity to ERα-mediated signaling during simulated energy insufficiency. The results also imply that estrogen promotes glucose and lactate uptake by these cells under those conditions. Evidence for correlation between hindbrain AMPK and hypothalamic nerve cell genomic activation provides novel proof for functional connectivity between this hindbrain sensor and higher order metabolic brain loci while demonstrating a modulatory role for estrogen in this interaction.

Median aperture of the fourth ventricle revisited.

BACKGROUND: The median aperture of Magendie is the largest of three openings of the fourth ventricle and thus it forms the main path for the outflow of the cerebrospinal fluid from the ventricle. The Magendie aperture connects the fourth ventricle with the cisterna magna and makes a natural corridor for neurosurgical approach and inspection of the ventricle and its floor. The purpose of this study was to give a contemporary anatomical view of this structure in the context of historical data. MATERIAL AND METHODS: The Magendie foramen was studied in 30 fixed specimens of human brainstems with cerebella. The microdissection technique was used. Measurements were taken with a microscope ocular ruler. RESULTS: The aperture is limited by the following structures: obex and gracile tubercles inferiorly, and tela choroidea with choroid plexus superolaterally. Obex tubercles usually have the form of a piece of neural tissue bridging two halves of the brainstem above the entrance to the central canal. Gracile tubercles together are 8.15 mm wide and the maximal width of the foramen is 6.53 mm. Tela choroidea attaches laterally at both sides to the inferior medullary velum. In most cases the right and left choroid plexus are connected to each other with a triangular membrane of tela choroidea, which protrudes through the median foramen and attaches to the vermis at a highly variable level. CONCLUSIONS: We hope that the presented description of anatomical relations around the Magendie aperture, with its new measurements, will be helpful for those operating in the area and will explain some of the inaccuracies found in literature.

Inter-fastigial projections along the roof of the fourth ventricle.

The fastigial nucleus (FN) is a bilateral cerebellar integrative center for saccadic and vestibular control associated with non-motor functions such as feeding and cardiovascular regulation. In a previous study, we identified a tract of myelinated axons embedded in the subventricular zone (SVZ) that is located between the ependymal cells that form the dorsal wall of the ventricle and the glia limitans at the roof of the fourth ventricle González-González (Sci Rep 2017, 7:40768). Here, we show that this tract of axons, named subventricular axons or SVa, contains projection neurons that bilaterally interconnect both FNs. The approach consisted of the use of a battery of fluorescent neuronal tracers, transgenic mouse lines, and immunohistofluorescence. Our observations show that the SVa belong to a wide network of GABAergic projection neurons mainly located in the medial and caudal region of the FN. The SVa should be considered a part of a continuum of the cerebellar white matter that follows an alternative pathway through the SVZ, a region closely associated with the physiology of the fourth ventricle. This finding adds to our understanding of the complex organization of the FN; however, the function of the interconnection remains to be elucidated.

Insight into the patterns of cerebrospinal fluid flow in the human ventricular system using MR velocity mapping.

The patterns of cerebrospinal fluid (CSF) flow within the human ventricular system are still not fully understood in all their complexity. Knowledge is based on either the interpretation of CSF flow curves or computational simulations. Both approaches only provide an incomplete insight into the spatial and temporal dynamics of CSF flow. Time-resolved three-dimensional magnetic resonance velocity mapping has previously been used to investigate normal and pathologic blood flow patterns in the human vascular system. Here we used this technique to study the spatial and temporal dynamics of CSF flow in the ventricular system of 40 normal volunteers. Classification of the patterns of CSF flow based on calculation of three-dimensional particle path lines over the cardiac cycle revealed one uniform flow pattern for the lateral ventricles, three categories for the third and two categories for the fourth ventricle. We found no significant aging effects on either the presence of a specific CSF flow pattern or on CSF flow velocities. Our results provide the first detailed demonstration of the patterns of CSF flow within the human ventricular system.

Selective blockade of the rat brain aqueduct with thermogelling hydrogel nanoparticle dispersion.

Experimental methods targeting molecules or drugs to specific neuronal tissue(s) can be important in determining function. In this study we focused on blockade of the small channel or aqueduct connecting the third and fourth ventricles of the rat brain. A cannula was placed into the aqueduct between the third and fourth ventricle. A second cannula was placed into the third or fourth ventricle. An aqueous dispersion of hydrogel nanoparticles, that maintains a liquid state at temperatures below 33 degrees C and solidifies near body temperature (35 degrees C), was infused into the aqueduct. Two interpenetrating polymer networks (IPN) of hydrogel nanoparticles with polymer concentrations at 2% by weight and 3% by weight were separately infused into the aqueduct to block cerebrospinal fluid (CSF) flow. Following infusion of hydrogel CSF was isolated to a particular ventricle as shown by the lack of dye movement between the ventricles. In addition, stress hormone, corticosterone, feeding behavior and blood glucose levels were measured. Results show upon reaching the aqueduct the hydrogel dispersion solidified and restricted the flow of CSF. A higher concentration of dispersion (3% wt.) was more effective in blocking the aqueduct and isolating the third from the fourth ventricle. Over the period of measurement, infusion of the dispersion had no measurable detrimental physiological effects on the animal. We conclude that isolation of ventricles in the brain can be completed for 48-h by using dispersions of hydrogel nanoparticles and the effects of drugs on certain brain tissues can be determined with this method.

The circumventricular organs: an atlas of comparative anatomy and vascularization.

The circumventricular organs are small sized structures lining the cavity of the third ventricle (neurohypophysis, vascular organ of the lamina terminalis, subfornical organ, pineal gland and subcommissural organ) and of the fourth ventricle (area postrema). Their particular location in relation to the ventricular cavities is to be noted: the subfornical organ, the subcommissural organ and the area postrema are situated at the confluence between ventricles while the neurohypophysis, the vascular organ of the lamina terminalis and the pineal gland line ventricular recesses. The main object of this work is to study the specific characteristics of the vascular architecture of these organs: their capillaries have a wall devoid of blood-brain barrier, as opposed to central capillaries. This particular arrangement allows direct exchange between the blood and the nervous tissue of these organs. This work is based on a unique set of histological preparations from 12 species of mammals and 5 species of birds, and is taking the form of an atlas.

Glucagon-Like Peptide-1 Receptor Activation in the Ventral Tegmental Area Decreases the Reinforcing Efficacy of Cocaine.

Cocaine addiction continues to be a significant public health problem for which there are currently no effective FDA-approved treatments. Thus, there is a clear need to identify and develop novel pharmacotherapies for cocaine addiction. Recent evidence indicates that activation of glucagon-like peptide-1 (GLP-1) receptors in the ventral tegmental area (VTA) reduces intake of highly palatable food. As the neural circuits and neurobiological mechanisms underlying drug taking overlap to some degree with those regulating food intake, these findings suggest that activation of central GLP-1 receptors may also attenuate cocaine taking. Here, we show that intra-VTA administration of the GLP-1 receptor agonist exendin-4 (0.05 µg) significantly reduced cocaine, but not sucrose, self-administration in rats. We also demonstrate that cocaine taking is associated with elevated plasma corticosterone levels and that systemic infusion of cocaine activates GLP-1-expressing neurons in the nucleus tractus solitarius (NTS), a hindbrain nucleus that projects monosynaptically to the VTA. To determine the potential mechanisms by which cocaine activates NTS GLP-1-expressing neurons, we microinjected corticosterone (0.5 µg) directly into the hindbrain fourth ventricle. Intraventricular corticosterone attenuated cocaine self-administration and this effect was blocked in animals pretreated with the GLP-1 receptor antagonist exendin-(9-39) (10 µg) in the VTA. Finally, AAV-shRNA-mediated knockdown of VTA GLP-1 receptors was sufficient to augment cocaine self-administration. Taken together, these findings indicate that increased activation of NTS GLP-1-expressing neurons by corticosterone may represent a homeostatic response to cocaine taking, thereby reducing the reinforcing efficacy of cocaine. Therefore, central GLP-1 receptors may represent a novel target for cocaine addiction pharmacotherapies.

Hypoglycemia activates orexin neurons and selectively increases hypothalamic orexin-B levels: responses inhibited by feeding and possibly mediated by the nucleus of the solitary tract.

Orexins are novel appetite-stimulating peptides expressed in the lateral hypothalamic area (LHA), and their expression is stimulated by hypoglycemia in fasted rats. We investigated activation of orexin and other neurons during insulin-induced hypoglycemia using the immediate early gene product Fos. Insulin (50 U/kg) lowered plasma glucose by >50% after 5 h and stimulated feeding sixfold compared with saline-injected controls. Hypoglycemic rats allowed to feed and normoglycemic controls both showed sparse Fos-positive (Fos+) neurons in the LHA and the paraventricular nucleus (PVN) and arcuate nucleus (ARC) and showed none in the nucleus of the solitary tract (NTS), which relays visceral feeding signals to the LHA. In the LHA, total numbers of Fos+ neurons were comparable in fed hypoglycemic and control groups (60 +/- 6 vs. 52 +/- 4 cells/mm2, P > 0.05), as were Fos+ neurons immunoreactive for orexin (1.4 +/- 0.4 vs. 0.6 +/- 0.4 cells/mm2, P > 0.05). By contrast, hypoglycemic rats that were fasted showed significantly more Fos+ nuclei in the LHA (96 +/- 10 cells/mm2, P < 0.05, vs. both other groups) and Fos+ orexin neurons (8.4 +/- 3.3 cells/mm2, P < 0.001, vs. both other groups). They also showed two- to threefold more Fos+ nuclei (P < 0.001) in the PVN and ARC than both fed hypoglycemic rats and controls and showed strikingly abundant Fos+ neurons in the NTS and dorsal motor nucleus of the vagus. In parallel studies, whole hypothalamic orexin-A levels were not changed in hypoglycemic rats, whether fasted or freely fed, whereas orexin-B levels were 10-fold higher in hypoglycemic fasted rats than in control and hypoglycemic fed groups. These data support our hypothesis that orexin neurons are stimulated by falling glucose levels but are readily inhibited by signals related to nutrient ingestion and suggest that they may functionally link with neuronal activity in the NTS. Orexin-A and -B may play specific roles in behavioral or neuroendocrine responses to hypoglycemia.

Involvement of imidazoline receptors in the baroreflex effects of rilmenidine in conscious rabbits.

OBJECTIVE: It has been suggested that imidazoline receptors rather than alpha2-adrenoceptors are involved in the sympathoinhibitory action of centrally acting antihypertensive drugs such as rilmenidine. In the present study, we examined the relative importance of alpha2-adrenoceptors and imidazoline receptors in modulating the renal sympathetic and heart rate (HR) baroreflex in response to central administration of rilmenidine in conscious normotensive rabbits. METHODS: In seven conscious rabbits, chronically instrumented with a fourth ventricular (4V) catheter, aortic and vena caval cuff occluders and a renal nerve electrode, we continuously recorded renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and HR and assessed baroreflex MAP-RSNA and MAP-HR relationships with balloon-induced ramp rises and falls in MAP. Rabbits were treated with 4V rilmenidine (22 microg/kg) followed by 4V idazoxan (30 microg/kg; a mixed alpha2-adrenoceptor and imidazoline receptor antagonist) or 4V 2-methoxy-idazoxan (1 microg/kg; an alpha2-adrenoceptor antagonist with little affinity for imidazoline receptors). RESULTS: Rilmenidine lowered blood pressure by 24% and reduced both upper and lower plateaus of the renal sympathetic baroreflex curve, such that the RSNA range (difference between plateaus) was reduced by 40% (-32 +/- 10 normalized units). Curves were shifted to the left with the fall in MAP. Idazoxan restored MAP, maximum RSNA and the RSNA baroreflex range. By contrast the alpha2-adrenoceptor antagonist 2-methoxy-idazoxan caused only a partial recovery of MAP and RSNA baroreflex upper plateau and range (-9 +/- 2 mmHg, 29 and 33% lower than control). Both antagonists partially restored the HR baroreflex. CONCLUSION: These findings suggest that in conscious rabbits, both imidazoline receptors and alpha2-adrenoceptors are involved in the central antihypertensive and baroreflex actions of rilmenidine, but that activation of imidazoline receptors is more important for its renal sympathoinhibitory action.

Wake-promoting and sleep-suppressing actions of hypocretin (orexin): basal forebrain sites of action.

The hypocretins (orexins) are a newly identified peptide family comprised of two peptides, hypocretin-1 and hypocretin-2. Recent observations suggest an involvement of these peptides in the regulation of behavioral state. For example, these peptides are found in a variety of brain regions associated with the regulation of forebrain neuronal and behavioral activity states. Furthermore, when infused into the lateral ventricles in awake animals, hypocretin-1 elicits increased duration of waking beyond that observed in vehicle-treated animals. Previous studies have been limited to an examination of the sleep-wake effects of hypocretin-1 in awake animals. Currently, the sleep-wake effects of hypocretin-2 and the extent to which hypocretins can initiate waking in the sleeping animal remain unclear. To better characterize the wake-promoting actions of the hypocretins, the current studies examined the sleep-wake effects of varying doses (0.007, 0.07 and 0.7 nmol) of hypocretin-1 and hypocretin-2 when administered into sleeping rats (e.g. remote-controlled infusions). Infusions of hypocretin-1 and hypocretin-2 into the lateral ventricles elicited a short latency (0.7 nmol hypocretin-1; 93+/-30 s from the start of the 120-s infusion) increase in electroencephalographic, electromyographic, and behavioral indices of waking. These infusions also produced substantial decreases in slow-wave and rapid-eye movement sleep. Hypocretin-1 was more potent than hypocretin-2 in these actions. Interestingly, hypocretin-1 infused into the fourth ventricle elicited less robust waking which occurred with a longer latency than infusions into the lateral ventricles. These latter observations suggest a forebrain site of action participates in hypocretin-1-induced waking. Within the forebrain, a variety of basal forebrain structures, including the medial preoptic area, the medial septal area and the substantia innominata, receive a moderate hypocretin innervation. Therefore, additional studies examined the sleep-wake effects of bilateral hypocretin-1 infusions into these basal forebrain structures. Robust increases in waking were observed following infusions into, but not outside, the medial septal area, the medial preoptic area and the substantia innominata. These results indicate a potentially prominent role of hypocretins in sleep-wake regulation via actions within certain basal forebrain structures and are consistent with studies indicating a prominent role of hypocretins in sleep/arousal disorders.

Implantation of neural stem cells via cerebrospinal fluid into the injured root.

In avulsion injury of the dorsal root, regenerating axons cannot extend through the entry zone, i.e. the transition zone between peripheral and central nervous systems, due to the discontinuity between Schwann cells and astrocytes. We infused neural stem cells through the 4th ventricle in an attempt to enhance axonal growth in injured dorsal roots. Infused stem cells were attached to, and integrated into, the lesion of the root and became associated with axons in the same manner as Schwann cells or perineurial sheath cells in the peripheral nerve, and as astrocytes in the central nerve area. These findings suggest that neural stem cells integrated by infusion through CSF might have a beneficial effect on nerve regeneration by inducing a continuity of Schwann cells and astrocytes at the transition zone.

Viscerotopic representation of the subdiaphragmatic tracts of the digestive apparatus within the vagus complex in the sheep.

The distribution in the brainstem and cervical spinal cord of neurons supplying the reticulum and the reticular groove, the rumen, the omasum, the abomasum, and the small and large intestine was investigated in the sheep using the fluorescent retrograde tracer technique. Only the reticulum and reticular groove were represented in the dorsal motor nucleus of the vagus nerve (DMNX), in the nucleus ambiguus (NA), and in the nucleus retroambigualis (NRA). The other forestomach, the abomasum and the small intestine were supplied by the DMNX only, with the exception of the rumen which was also innervated by the NRA. Some reticular formation neurons were found labeled after the injection of the tracer into the reticulum, the reticular groove, and the rumen. We present evidence that the reticular groove is the part of the forestomach having the widest representation, and also the richest innervation.

Discrete regions in the laterodorsal tegmental area of the rat regulating the urinary bladder and external urethral sphincter.

In urethane anesthetized rats, the laterodorsal tegmental area was stimulated systematically with a carbon fiber electrode to clarify regions regulating the urinary bladder and/or the external urethral sphincter. Contraction of the former was monitored by bladder pressure and that of the latter by electromyogram. Stimulation of a small area around the ventrolateral edge of the central gray in a plane at the junction of the mesencephalon and pons, where cholinergic neurons in the laterodorsal tegmental nucleus formed the largest mass, induced contraction only of the bladder. Arranged in tandem rostrocaudally with this bladder site, a very small area whose stimulation induced contraction only of the sphincter was found also at the ventrolateral edge of the central gray in a plane slightly caudal to the above. Slightly lateral and caudal to this sphincter site, there were sites the stimulation of which induced contraction of both the bladder and sphincter. It was thus shown physiologically that there were discrete sites in the laterodorsal tegmental area regulating the bladder and sphincter independently.

CART in the dorsal vagal complex: sources of immunoreactivity and effects on Fos expression and food intake.

CART-peptide (CARTp) has been shown to suppress food intake, particularly when injected into the 4th ventricle of rats, and the presence of CART in nodose ganglia suggested a role in satiation. Based on retrograde tracing from the DVC combined with CART immunohistochemistry and supranodose vagotomy, we found that CART immunoreactivity in varicose fibers of the dorsal vagal complex originates from vagal afferents, sparse projections from the medullary reticular formation and the arcuate/retrochiasmatic nucleus of the hypothalamus, and most likely also from local CART neurons in the area postrema and NTS. In the nodose ganglia, 17% of neurons with projections to the stomach and 41% to the duodenum express CART-IR. CART-IR vagal afferents significantly contribute to the rich fiber plexus in mainly the commissural NTS and the adjacent area postrema. Injections of CARTp into the 4th ventricle strongly suppressed sucrose drinking and stimulated expression of c-Fos in the NTS. Injections of CARTp directly into various subnuclei of the NTS were less effective in suppressing food intake. The findings suggest that the critical site for CART's suppression of food intake is not in the termination zone of CART-containing vagal afferents in the commissural NTS, and that CART release from vagal afferent terminals plays a minor role in satiation. The functional role of CART in vagal afferents and the site of food intake suppression by 4th ventricular CARTp remain to be determined.

New method for transplantation of neurosphere cells into injured spinal cord through cerebrospinal fluid in rat.

Here we report a novel method of supplying cultured neurosphere cells to the injured spinal cord, by injection of cells into the cerebrospinal fluid (CSF) through the fourth ventricle or cisterna magna. Hippocampus-derived neurosphere cells, isolated from a transgenic rat fetus expressing green fluorescent protein, were transplanted into the CSF of a rat with spinal cord injury. It was found that injected cells were extensively transported by CSF within the subarachnoidal space, and survived as clusters on the pial surface of the spinal cord. The most notable finding was that a large number of injected cells migrated into the lesion site and integrated into the injured spinal cord tissues.

Electrophysiological properties of the rat area postrema neurons displaying both the transient outward current and the hyperpolarization-activated inward current.

We found coexistence of the transient outward potassium current (I(TO)) and the hyperpolarization-activated inward current (I(H)) in 26 of 82 area postrema neurons tested using the whole-cell patch-clamp technique in rat brain slices. Cells displaying both the I(TO) and the I(H) typically showed "voltage sag" and "rebound potentials" in response to hyperpolarizing current injection and repetitive firing with strong adaptation was seen with depolarizing current injection. When cells were held at membrane potentials more negative than the resting level (e.g., -85mV), the afterhyperpolarization was enhanced. Voltage clamp recordings were performed to examine the characteristics of I(TO) and I(H) in and the contributions of these currents to the electroresponsiveness of area postrema cells. We show, in this study, the voltage-dependent properties of I(H) and I(TO), and how these currents modulate the intrinsic membrane properties of area postrema cells. We discuss the functional significance of the specific subset of area postrema neurons whose cells have both I(H) and I(TO) channels.

Dual action of olivocochlear collaterals in the guinea pig cochlear nucleus.

Axons of olivocochlear neurones in the superior olivary complex terminate on hair cells of the cochlea, reducing the sensitivity to sound. These axons also have collateral branches to neurones in the cochlear nucleus, the first processing centre in the brainstem. Anatomical data show that these collaterals terminate mainly in the granule cell area but their precise neuronal targets and the effects they might have are unknown. We have studied the effects of these collaterals in guinea pigs, by electrically stimulating the olivocochlear axons at the floor of the IVth ventricle while recording single neurone responses in the cochlear nucleus. We eliminated the peripheral effects of olivocochlear stimulation either by destruction of the target receptor cells using chronic administration of kanamycin, or by acute perfusion of the cochlea with strychnine, a specific blocker of the postsynaptic receptors. Electrical stimulation of the olivocochlear axons in normal animals caused a variety of effects on cochlear nucleus neurones. In some neurones, there was suppression of spontaneous firing and a reduction in sensitivity to sound, while in others there was an excitatory effect of olivocochlear axon stimulation. When the peripheral olivocochlear action was eliminated, we still found both inhibition and excitation in the cochlear nucleus. These results show that the effects of olivocochlear stimulation on cochlear nucleus responses are not a simple passive reflection of peripheral changes but are a result of complex interactions between peripheral suppression of afferent input and collateral-mediated excitation and possibly also inhibition.

Subdiaphragmatic vagotomy induces NADPH diaphorase in the rat dorsal motor nucleus of the vagus.

Axotomy of the vagal motor neurons by cervical vagotomy induces NADPH diaphorase staining due to increased nitric oxide synthase expression in both the rat dorsal motor nucleus and nucleus ambiguous; furthermore, cerical vagotomy leads to cell death of the dorsal motor nucleus cells. Subdiaphragmatic vagotomy axotomizes the vagal motor cells further from the brainstem than cervical vagotomy, and cuts the fibers running only to the abdominal viscera. Here we report that subdiaphragmatic vagotomy is sufficient to induce NADPH diaphorase staining in the dorsal motor nucleus but does not induce staining in the nucleus ambiguus. Because the neurons of the dorsal motor nucleus do not undergo cell death after subdiaphragmatic vagotomy and are able to re-enervate the gut, the increased nitric oxide synthase expression after distal axotomy may be related more to regeneration than degeneration.

Role of the area postrema of medulla oblongata in the regulation of canine interdigestive migrating motor complex.

OBJECTIVE: To determine the effect of the area postrema (AP) of the medulla oblongata on gastrointestinal interdigestive migrating motor complex (MMC) and the plasma motilin level. METHODS: Interdigestive MMC activities of the antrum and duodenum were recorded by strain gauge implanted on the serosa of 8 conscious dogs. A cannula was intubated in femoral vein for motilin injection. The plasma motilin concentration was measured by RIA. We observed: (1) normal interdigestive MMC activity and fluctuations in plasma motilin concentration; (2) the effects of electrically damaging the AP on MMC activity and plasma motilin level; (3) whether intravenous injection of motilin could induce phase III contractions after the AP was destroyed. RESULTS: (1) Typical interdigestive MMC with phase I, II, III, and IV was recorded in normal dogs. Phase III was concurrent with the peak of plasma motilin level. (2) In damaged AP dogs, antroduodenal interdigestive MMC contractions were suppressed; cyclic, phasic and migratory pattern of MMC was disrupted. Plasma motilin concentration was decreased. Intravenous injection of motilin could not induce phase III contractions. CONCLUSIONS: The area postrema might play an important role, which is mediated by motilin, on the regulation of interdigestive MMC.