Vasoactive intestinal polypeptide excites medial pontine reticular formation neurons in the brainstem rapid eye movement sleep-induction zone.
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Although it has long been known that microinjection of the cholinergic agonist carbachol into the medial pontine reticular formation (mPRF) induces a state that resembles rapid eye movement (REM) sleep, it is likely that other transmitters contribute to mPRF regulation of behavioral states. A key candidate is the peptide vasoactive intestinal polypeptide (VIP), which innervates the mPRF and induces REM sleep when injected into this region of the brainstem. To begin understanding the cellular mechanisms underlying this phenomenon, we examined the effects of VIP on mPRF cells using whole-cell patch-clamp recordings in the in vitro rat brainstem slice. VIP directly depolarized cells via activation of an inward current; these effects were attenuated and potentiated in low-sodium and low-calcium medium, respectively. The depolarization induced by VIP was slower in onset and longer-lived than that evoked by carbachol. The VIP-induced depolarization was reduced in a dose-dependent manner by a competitive antagonist of VIP receptors. Effects of VIP were attenuated in the presence of guanosine 5'-O-(2-thiodiphosphate, 2'5'dideoxyadenosine, and PKI15-24 and were nonadditive in the presence of 8-bromo-cAMP. We conclude that VIP excites mPRF neurons by activation of a sodium current. This effect is mediated at least in part by G-protein stimulation of adenylyl cyclase, cAMP, and protein kinase A. These data suggest that VIP may play a physiological role in REM induction by its actions on mPRF neurons. (+info)
Remote regional cerebral blood flow consequences of focused infarcts of the medulla, pons and cerebellum.
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The aim of this study was to evaluate regional and remote diaschisis of inferior brain stem or cerebellar infarcts in 25 patients presenting with relatively limited lesions. Patients presented with medullary, pontine or cerebellar infarction. METHODS: Lesions were evaluated on MRI (0.5 T). Regional cerebral blood flow (rCBF) was assessed by means of SPECT, after injection of 9rmTc-hexamethyl propyleneamine oxime (HMPAO) and, when possible, inhalation of 133Xe in the same session. For each method, asymmetry indices (Als), comparing contralateral to ipsilateral rCBF values, were calculated in four areas of each cerebral hemisphere and in the cerebellum and later compared with values obtained in healthy subjects (P = 0.05). RESULTS: Higher rCBF values were observed in the contralateral cerebellum in 2 of 7 patients with selective lateral medullary lesions, and cerebellar Als were significantly increased. When a cerebellar infarct was associated with a lateral medullary lesion, the cerebellar and contralateral hemispheric asymmetries were more severe. Unilateral paramedian pontine infarcts had more frequent consequences on the cerebellum (2 of 3 cases), with rCBF or tracer uptake being reduced in the ipsilateral or the contralateral lobe. Inverse cerebral hemispheric asymmetry could then be observed. Bilateral pontine lesions were difficult to evaluate. Using 99mTc-HMPAO, discrete cerebellar asymmetry was observed in 3 of 6 cases. Pure cerebellar infarcts in the posterior inferior cerebellar artery territory were always associated with a severe ipsilateral flow drop in the cerebellum, and contralateral hemispheric diaschisis was frequent (3 of 4 patients), predominating in the frontotemporal cortex and subcortical structures. This was also more obvious using 99mTC-HMPAO than 133Xe. Variance analysis showed that hemispheric diaschisis was more severe in mixed brain stem and cerebellar infarcts than in pure cerebellar or brain stem lesions. Furthermore, cerebellar and hemispheric AI values were not correlated with measurements of clinical deficits, disability or handicap. CONCLUSION: Unilateral and limited inferior brain stem lesions can have ipsi- or contralateral consequences on the cerebellum and cerebral hemispheres rCBF. These remote effects are related to lesions of the main pathways joining these structures, resulting in deactivation and, in some cases, overactivation. Contrary to what has been suggested, consequences on cerebral hemispheres are more severe in mixed cerebellar and brain stem infarcts than in pure cerebellar lesions. (+info)
Central pain after pontine infarction is associated with changes in opioid receptor binding: a PET study with 11C-diprenorphine.
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Using 18F-fluorodeoxyglucose and 11C-diprenorphine positron emission tomography (PET), we investigated alterations in glucose metabolism and opioid receptor binding in a patient with central poststroke pain, which developed after a small pontine hemorrhagic infarction. In comparison with normal databases, reduced 11C-diprenorphine binding was more accentuated than the hypometabolism on the lateral cortical surface contralateral to the symptoms, and a differential abnormal distribution between the tracers was seen in pain-related central structures. These results show that 11C-diprenorphine PET provides unique information for the understanding of central poststroke pain. (+info)
Glutamatergic projection to RVLM mediates suppression of reflex bradycardia by parabrachial nucleus.
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We investigated the role of glutamatergic projection from the parabrachial nucleus (PBN) complex to the rostral ventrolateral medulla (RVLM) in the PBN-induced suppression of reflex bradycardia in adult Sprague-Dawley rats that were maintained under pentobarbital anesthesia. Under stimulus conditions that did not appreciably alter the baseline systemic arterial pressure and heart rate, electrical (10-s train of 0.5-ms pulses, at 10-20 microA and 10-20 Hz) or chemical (L-glutamate, 1 nmol) stimulation of the ventrolateral regions and Koelliker-Fuse (KF) subnucleus of the PBN complex significantly suppressed the reflex bradycardia in response to transient hypertension evoked by phenylephrine (5 micrograms/kg iv). The PBN-induced suppression of reflex bradycardia was appreciably reversed by bilateral microinjection into the RVLM of the N-methyl-D-aspartate (NMDA)-receptor antagonist MK-801 (500 pmol) or the non-NMDA-receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione (50 pmol). Anatomically, most of the retrogradely labeled neurons in the ventrolateral regions and KF subnucleus of the ipsilateral PBN complex after microinjection of fast blue into the RVLM were also immunoreactive to anti-glutamate antiserum. These results suggest that a direct glutamatergic projection to the RVLM from topographically distinct regions of the PBN complex may participate in the suppression of reflex bradycardia via activation of both NMDA and non-NMDA receptors at the RVLM. (+info)
Collapsin-1/semaphorin-III/D is regulated developmentally in Purkinje cells and collapses pontocerebellar mossy fiber neuronal growth cones.
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Most axons in the CNS innervate specific subregions or layers of their target regions and form contacts with specific types of target neurons, but the molecular basis of this process is not well understood. To determine whether collapsin-1/semaphorin-III/D, a molecule known to repel specific axons, might guide afferent axons within their cerebellar targets, we characterized its expression by in situ hybridization and observed its effects on mossy and climbing fiber extension and growth cone size in vitro. In newborn mice sema-D is expressed by cerebellar Purkinje cells in parasagittal bands located medially and in some cells of the cerebellar nuclei. Later, sema-D expression in Purkinje cells broadens such that banded expression is no longer prominent, and expression is detected in progressively more lateral regions. By postnatal day 16, expression is observed throughout the cerebellar mediolateral axis. Collapsin-1 protein, the chick ortholog of sema-D, did not inhibit the extension of neurites from explants of inferior olivary nuclei, the source of climbing fibers that innervate Purkinje cells. In contrast, when it was applied to axons extending from basilar pontine explants, a source of mossy fiber afferents of granule cells, collapsin-1 caused most pontine growth cones to collapse, as evidenced by a reduction in growth cone size of up to 59%. Moreover, 63% of pontine growth cones arrested their extension or retracted. Its effects on mossy fiber extension and its distribution suggest that sema-D prevents mossy fibers from innervating inappropriate cerebellar target regions and cell types. (+info)
Visceral afferent activation-induced changes in sympathetic nerve activity and baroreflex sensitivity.
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The following experiments were done to determine whether changes in baroreflex sensitivity evoked by cervical vagus nerve stimulation are due to sympathoexcitation mediated by the parabrachial nucleus. The relative contribution of cardiopulmonary and general gastric afferents within the cervical vagus nerve to the depression in baroreflex sensitivity are also investigated. Male Sprague-Dawley rats anesthetized with thiobutabarbital sodium (50 mg/kg) were instrumented to measure blood pressure and heart rate or for the continuous monitoring of renal sympathetic nerve activity. Baroreflex sensitivity was measured using bolus injections of phenylephrine. Electrical stimulation of the cervical vagus (with or without the aortic depressor nerve) or the abdominal vagus nerve produced a significant increase in renal nerve activity and a decrease in baroreflex sensitivity. Both of these effects were blocked after the microinjection of lidocaine into the parabrachial nucleus before nerve stimulation. Therefore, we conclude that an increase in the activity of cardiac, pulmonary, or general gastric afferents mediated the increased sympathetic output and decreased baroreflex sensitivity via a pathway involving the parabrachial nucleus. (+info)
Physiological properties of neurons in the ventral nucleus of the lateral lemniscus of the rat: intrinsic membrane properties and synaptic responses.
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The physiological properties including current-voltage relationships, firing patterns, and synaptic responses of the neurons in the ventral nucleus of the lateral lemniscus (VNLL) were studied in brain slices taken through the young rat's (17-37 days old) auditory brain stem. Intracellular recordings were made from VNLL neurons, and synaptic potentials were elicited by electrical stimulation of the lateral lemniscus ventral to the VNLL. Current-voltage relations and firing patterns were tested by recording the electrical potentials produced by intracellular injection of positive and negative currents. There were two types of VNLL neurons (type I and II) that exhibited different current-voltage relationships. In response to negative current, both type I and II neurons produced a graded hyperpolarization. Type I neurons responded to positive current with a graded depolarization and multiple action potentials the number of which was related to the strength of the current injected. The current-voltage relations of type I neurons were nearly linear. Type II neurons responded to positive current with a limited depolarization and only one or a few action potentials. The current-voltage relations of type II neurons were nonlinear near the resting potential. The membrane properties of the type II VNLL neurons may play an important role for processing information about time of onset of a sound. Type I neurons showed three different firing patterns, i.e., regular, onset-pause and adaptation, in response to small positive current. The onset-pause and adaptation patterns could become sustained when a large current was injected. The regular, onset-pause, and adaptation patterns in type I neurons and the onset pattern in type II neurons resemble "chopper," "pauser, " "primary-like," and "on" responses, respectively, as defined in in vivo VNLL studies. The results suggest that different responses to acoustic stimulation could be attributed to intrinsic membrane properties of VNLL neurons. Many VNLL neurons responded to stimulation of the lateral lemniscus with excitatory or inhibitory responses or both. Excitatory and inhibitory responses showed interaction, and the output of the synaptic integration depended on the relative strength of excitatory and inhibitory responses. Neurons with an onset-pause firing pattern were more likely to receive mixed excitatory and inhibitory inputs from the lower auditory brain stem. (+info)
Hypothalamopontine projections in the rat: anterograde axonal transport studies utilizing light and electron microscopy.
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Projections to the basilar pontine nuclei (BPN) from a variety of hypothalamic nuclei were traced in the rat utilizing the anterograde transport of biotinylated dextran amine. Light microscopy revealed that the lateral hypothalamic area (LH), the posterior hypothalamic area (PH), and the medial and lateral mammillary nuclei (MMN and LMN) are the four major hypothalamic nuclei that give rise to labeled fibers and terminals reaching the rostral medial and dorsomedial BPN subdivisions. Hypothalamopontine fibers extended caudally through the pontine tegmentum dorsal to the nucleus reticularis tegmenti pontis and then coursed ventrally from the main descending bundle toward the ipsilateral basilar pontine gray. Some hypothalamopontine fibers crossed the midline in the tegmental area just dorsal to the pontine gray to terminate in the contralateral BPN. Electron microscopy revealed that the ultrastructural features of synaptic boutons formed by axons arising in the LH, PH, MMN, and LMN are similar to one another. All labeled hypothalamopontine axon terminals contained round synaptic vesicles and formed asymmetric synaptic junctions with dendritic shafts as well as dendritic appendages, and occasionally with neuronal somata. Some labeled boutons formed the central axon terminal in a glomerular synaptic complex. In summary, the present findings indicate that the hypothalamus projects predominantly to the rostral medial and dorsomedial portions of the BPN which, in turn, provide input to the paraflocculus and vermis of the cerebellum. Since the hypothalamic projection zones in the BPN also receive cerebral cortical input, including limbic-related cortex, the hypothalamopontine system might serve to integrate autonomic or limbic-related functions with movement or somatic motor-related activity. Alternatively, since the cerebellum also receives direct input from the hypothalamus, the BPN may function to provide additional somatic and visceral inputs that are used by the cerebellum to perform the integrative function. (+info)