Reinfection with the agent of human granulocytic ehrlichiosis

1. The functional role of the paraventricular nucleus (PVN) has been examined by studying its connections with cardiovascular neurons in the medulla and spinal cord and its influence on activity in several sympathetic nerves. 2. Chemical stimulation of neurons within the PVN can elicit pressor responses and can excite reticulo-spinal vasomotor neurons in the rostral ventrolateral medulla (RVLM). 3. The PVN-RVLM excitation is blocked by kynurenic acid applied iontophoretically in the vicinity of RVLM-spinal neurons, suggesting this is a glutamate-dependent pathway. 4. Electrical stimulation of PVN neurons evoked action potentials in RVLM neurons after 27 ms with a small variability. 5. Anterograde and retrograde labelling of PVN and RVLM neurons revealed PVN terminals closely associated with RVLM-spinal neurons and showed that the PVN is connected to the spinal cord via three pathways. 6. Chemical activation of PVN neurons can produce a pattern of activation of cardiovascular neurons similar to that occurring in defence against plasma volume expansion. 7. It is concluded that the PVN connections with the RVLM and spinal cord are important to a role in defending against life-threatening disturbances.     

Dobzhansky''s genetics and the origin of species: is it still relevant?

The activity and regional distribution of D-amino acid oxidase (DAO), an enzyme that inactivates D-serine, were examined in the medulla and spinal cord of the rat by biochemical and histochemical procedures. DAO activity was noticeably low or absent in the nucleus of the solitary tract, ventrolateral medulla and intramediolateral cell column of the spinal cord. This may be indicative of a neuromodulatory role for endogenous D-serine (at the NMDA-glycine site) in in the central control of blood pressure.     

Itraconazole oral solution versus clotrimazole troches for the treatment of oropharyngeal candidiasis in immunocompromised patients

The development of the nervous system appears to be under the control of multiple growth factors, neurotrophins and cytokines, which may be expressed either continuously or transiently throughout defined stages of cellular generation, proliferation or differentiation. Fibroblast growth factor (FGF) cytokines and their receptors are abundantly expressed in the embryonic nervous system but their localization at autonomic levels in the fetal spinal cord has not yet been detailed. Immunoreactivity to FGF-2, probably the best characterized member of the FGF family (FGF-1 to FGF-10) and of one of its high affinity receptors, FGFR-1, was found in autonomic neurons at embryonic day E14, the peak day of generation and proliferation in the common ventral motoneuron pool. It was also continuously present throughout the investigated subsequent stages (E15 to postnatal day P30). Immunogold electron microscopy revealed the cytoplasmic localization of FGF-2 and FGFR-1 in intermediolateral neurons, the major group of sympathetic preganglionic neurons in the spinal cord. In these neurons, immunocytochemistry from E14 onwards showed the co-distribution of both markers at the period of axonal outgrowth to peripheral targets, e.g. the adrenal medulla. Our findings suggest autocrine and/or paracrine actions of FGF-2 for sympathetic preganglionic development but do not support its role as a target-derived neurotrophic factor for autonomic neuron development.     

Systemic administration of kainate induces marked increases of endogenous kynurenic acid in various brain regions and plasma of rats

The endogenous neuroinhibitory and neuroprotective excitatory amino acid receptor antagonist kynurenic acid has been hypothetically linked to the pathogenesis of epilepsy and several other brain disorders. In the present study, alterations in kynurenic acid levels were examined in the kainate model of temporal lobe epilepsy. Kainate was systemically injected in rats at a dose (10 mg/kg s.c.) which induces a characteristic behavioural syndrome with stereotypies and focal (limbic) and generalized seizures, eventually progressing into severe status epilepticus. Kynurenic acid was determined 3 h after kainate injection in various brain regions (olfactory bulb, frontal cortex, piriform cortex, amygdala, hippocampus, nucleus accumbens, caudate/putamen, thalamus, superior and inferior colliculus, pons and medulla, and cerebellar cortex) and in plasma, using a sensitive high-performance liquid chromatographic method. When data were analysed irrespective of individual seizure severity, significant increases in kynurenic acid were determined in all brain regions examined except the hippocampus, nucleus accumbens and pons/medulla. The most marked (200-500%) increases above controls were seen in the piriform cortex, amygdala, and cerebellar cortex. Furthermore, a significant kynurenic acid increase of about 200% above control was determined in plasma. When kynurenic acid levels were determined in subgroups of rats with different behavioural alterations in response to kainate, the most marked kynurenic acid increases were seen in subgroups with status epilepticus. Rats which only developed mild (focal) seizures or stereotyped behaviours (wet dog shakes) also exhibited significantly increased kynurenic acid levels, thus indicating that the increase in kynurenic acid in response to kainate was not solely due to sustained convulsive seizure activity. Whereas it was previously proposed that kynurenic acid is involved only in later stages of seizure disorders, the present data demonstrate that marked increases in central and peripheral kynurenic acid levels occur early after the onset of neuroexcitation, at least in the kainate model.     

Galanin immunoreactive neurons in the medulla oblongata of rats

The distribution of galanin-immunoreactive (-ir) neurons in the medulla oblongata was mapped with light microscopic immunohistochemistry. No immunopositive perikarya were seen in untreated rats. Two days after colchicine treatment, galanin immuno-positive neurons were localized in the following areas: 1) raphe nuclei (magnus, pallidus and obscurus); 2) in various parts of the reticular formation, mainly in the territory of the catecholaminergic groups and in the peritrigeminal subdivision of the lateral reticular nucleus; 3) vagal nuclei (nucleus of the solitary tract, nucleus ambiguous); 4) two cell groups at the ventral surface of the rostro-caudal middle portion of the medulla oblongata (they do not correspond to any known demarkated anatomical nuclei, but related to the chemosensitive medullary area); 5) in the gelatinous part of the spinal trigeminal nucleus. The wide distribution of galanin neurons in the medulla support data that had been reported on the role of this peptide in various viscerosensory and autonomic mechanisms. In addition to these, galanin seems to be an important factor in the restoration of lesioned neurons (nerve growth factor-like activity). An increased galanin mRNA expression can be seen in dorsal vagal or hypoglossal motor neurons after intracranial transections of vagal or hypoglossal nerves, respectively. Transections of the olivocerebellar tract induced galanin gene expression in neurons of the contralateral inferior olive. After brainstem hemisection, galanin immunopositivity was seen in cells of the nucleus of the solitary tract due to the transection of ascending projections of this primary autonomic center in the medulla oblongata.     

Frequency and clinical correlates of occlusive lesions of cerebral arteries in Japanese patients without stroke. Evaluation by MR angiography

BACKGROUND: In order to provide a morphological basis for the understanding of the role of nitric oxide (NO) in autonomic preganglionic neurons, the present study was designed to clarify the localization and distribution of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity, a marker of NO synthase, in the rabbit spinal cord. METHODS: 11 Chinchilla rabbits of both sexes were used in this study. Animals were kept under conditions of controlled light and heat regimens. NADPH-d activity was examined by histochemical methods. RESULTS: The presence of NADPH-d activity in the spinal cord was detected in the dorsal horn, around the central canal (lamina X) and in autonomic preganglionic neurons. Focused on the latter, there was a prominent NADPH-d activity between T1 and L5 segments in the intermediate zone and less intensive NADPH-d staining between S1 and S3 segments. Differences between the two parts of the autonomic system were seen in the arrangement (periodical in sympathetic, and continuous in parasympathetic), in the length of neuronal processes length (shorter in sacral preganglionic neurons) and in their localization (both are seen in the intermediolateral nucleus, but neurons of the sympathetic autonomic system can be found also medially towards the central canal, whilst those of the parasympathetic system were not). CONCLUSIONS: The present results suggest that NO can be used as a transmitter in preganglionic neurons and can be involved in autonomic and sensory processes. (Fig. 10, Ref. 37.)     

Distribution and connections of inspiratory premotor neurons in the brainstem of the pigeon (Columba livia)

We have recorded extracellular, inspiratory-related (IR) unit activity in the medulla at locations corresponding to those of neurons retrogradely labeled by injections of retrograde tracers in the lower brachial and upper thoracic spinal cord, injections that covered cell bodies and dendrites of motoneurons innervating inspiratory muscles. Bulbospinal neurons were distributed throughout the dorsomedial and ventrolateral medulla, from the spinomedullary junction through about 0.8 mm rostral to the obex. Almost all of the 104 IR units recorded were located in corresponding parts of the ventrolateral medulla, rostral to nucleus retroambigualis, where expiratory related units are found. Injections of biotinylated dextran amine at the recording sites labeled projections both to the spinal cord and to the brainstem. In the lower brachial and upper thoracic spinal cord, bulbospinal axons traveled predominantly in the contralateral dorsolateral funiculus and terminated in close relation to the dendrites of inspiratory motoneurons retrogradely labeled with cholera toxin B-chain. In the brainstem, there were predominantly ipsilateral projections to the nucleus retroambigualis, tracheosyringeal motor nucleus (XIIts), ventrolateral nucleus of the rostral medulla, infraolivary superior nucleus, ventrolateral parabrachial nucleus, and dorsomedial nucleus of the intercollicular complex. In all these nuclei, except XIIts, retrogradely labeled neurons were also found, indicating reciprocity of the connections. These results suggest the possibility of monosynaptic connections between inspiratory premotor neurons and inspiratory motoneurons, which, together with connections of IR neurons with other brainstem respiratory-vocal nuclei, seem likely to mediate the close coordination that exists in birds between the vocal and respiratory systems. The distribution of IR neurons in birds is similar to that of the rostral ventral respiratory group (rVRG) in mammals.     

Preproenkephalin messenger RNA-expressing neurons in the rat parabrachial nucleus: subnuclear organization and projections to the intralaminar thalamus

The pontine parabrachial nucleus, which is a key structure in the central processing of autonomic, nociceptive and gustatory information, is rich in a variety of neuropeptides. In this study we have analysed the distribution of parabrachial neurons that express preproenkephalin messenger RNA, which encodes for the precursor protein for enkephalin opioids. Using an in situ hybridization method, we found that preproenkephalin messenger RNA-expressing neurons were present in large numbers in four major areas of the parabrachial nucleus: the K?lliker-Fuse nucleus, the external lateral subnucleus, the ventral lateral subnucleus, and in and near the internal lateral subnucleus. Many preproenkephalin messenger RNA-expressing neurons were also seen in the central lateral subnucleus, and in the medial and external medial subnuclei. Few labeled neurons were found in the dorsal and superior lateral subnuclei. Injection of the retrograde tracer substance cholera toxin subunit B into the midline and intralaminar thalamus demonstrated that the enkephalinergic neurons in and near the internal lateral subnucleus were thalamic-projecting neurons. Taken together with the results of previous tract-tracing studies, the present findings show that many of the enkephalinergic cell groups in the parabrachial nucleus are located within the terminal zones of the ascending projections that originate from nociresponsive neurons in the medullary dorsal horn and spinal cord, as well as from viscerosensory neurons within the nucleus of the solitary tract. The enkephalinergic neurons in the parabrachial nucleus may thus transmit noci- and visceroceptive-related information to their efferent targets. On the basis of the present and previous observations, we conclude that these targets include the intralaminar and midline thalamus, the ventrolateral medulla and the spinal cord. Through these connections, nociceptive and visceroceptive stimuli may influence several functions, such as arousal, respiration and antinociception.     

Localization of dopamine D2 receptor in rat spinal cord identified with immunocytochemistry and in situ hybridization

In the present study the distribution of dopamine D2 receptors in rat spinal cord was determined by means of immunocytochemistry using an anti-peptide antibody, directed against the putative third intracellular loop of the D2 receptor and in situ hybridization (ISH) using a [35S]UTP labelled anti-sense riboprobe. With the immunocytochemical technique, labelling was confined to neuronal cell bodies and their proximal dendrites. Strongest labelling was present in the parasympathetic area of the sacral cord and in two sexually dimorphic motor nuclei of the lumbosacral cord, the spinal nucleus of the bulbocavernosus and the dorsolateral nucleus. Moderately labelled cells were present in the intermediolateral cell column, the area around the central canal and lamina I of the dorsal horn. Weak labelling was present in the lateral spinal nucleus and laminae VII and VIII of the ventral horn. Except for the two sexually dimorphic motornuclei of the lumbosacral cord labelled motoneurons were not encountered. With the ISH technique radioactive labelling was present in many neurons, indicating that they contained D2 receptor mRNA. The distribution of these neurons was very similar to the distribution obtained with immunocytochemistry, but with ISH additional labelled cells were detected in laminae III and IV of the dorsal horn, which were never labelled with immunocytochemistry. The present study shows that the D2 receptor is expressed in specific areas of the rat spinal cord. This distribution provides anatomical support for the involvement of D2 receptors in modulating nociceptive transmission and autonomic control. Our data further indicate that D2 receptors are not directly involved in modulating motor functions with the exception, possibly, of some sexual motor functions.     

Sympathoexcitation from the rostral ventrolateral medulla is mediated by spinal NMDA receptors

These studies examined the role of spinal N-methyl-D-aspartic acid (NMDA) receptors in mediating sympathoexcitation evoked by stimulation of neurons in the rostral ventrolateral medulla (RVLM). In urethane-anesthetized rats, blood pressure, heart rate, and splanchnic sympathetic nerve activity (SNA) were recorded. The NMDA receptor antagonist D-2-amino-7-phosphonoheptanoic acid (D-AP7) was administered to the spinal cord via intrathecal (IT) catheter. Blockade of spinal NMDA receptors reduced arterial blood pressure, heart rate, and SNA. Spinal administration of D-AP7 markedly attenuated the pressor and sympathoexcitatory responses evoked by L-glutamate stimulation of the RVLM. The small increases in heart rate evoked by stimulation of the RVLM were not affected by IT administration of D-AP7. These results indicate that NMDA receptors in the spinal cord mediate the pressor and sympathoexcitatory responses evoked by activation of a bulbospinal pathway originating from the RVLM. Moreover, these data suggest that excitatory amino acid neurotransmitters and NMDA receptors in the spinal cord play an important role in the maintenance and regulation of SNA and cardiovascular function.     

Pharmacological characterization of N-methyl-D-aspartate receptors in spinal cord of rats with a chronic peripheral mononeuropathy

N-Methyl-D-aspartate (NMDA) receptor antagonists, acting in the spinal cord, are analgesic. However, the clinical utility of these antagonists is diminished by their adverse effects on cognition and behavior. To facilitate the development of spinal cord-selective NMDA receptor antagonists, we characterized ligand interactions at NMDA receptors in spinal cord of normal rats and rats with a chronic peripheral neuropathy. NMDA receptors in spinal cord were distinguished from those in cerebral cortex on the basis of differences in the potencies of competitive and noncompetitive antagonists and on the basis of differences in their response to spermidine. D(-)-2-Amino-5-phosphonopentanoic acid (AP-5) and (+)-(1-hydroxy-3-aminopyrrolidine-2-one) (HA-966) were more potent in inhibiting NMDA-dependent [3H]TCP binding in spinal cord while, conversely, MK-801 was more potent in inhibiting [3H]TCP binding to NMDA receptors in cerebral cortex. Spermidine increased [3H]TCP binding to NMDA receptors in cerebral cortex (39+/-8%) but not spinal cord (2+/-1%). Based on these properties, NMDA receptors in spinal cord more closely resembled those in cerebellum than those in cerebral cortex. Generation of a chronic neuropathy had no effect on the density of NMDA receptors in lumbar spinal cord. There were also no major changes in the potencies of competitive antagonists or channel blocking ligands, although there was a trend for kynurenic acid and D-CPP to be more potent in the spinal cords of neuropathic animals. These findings indicate that, in both normal and neuropathic pain states, NMDA receptors in spinal cord can be distinguished pharmacologically from those in cerebral cortex. These findings underscore the feasibility of developing spinal cord-selective NMDA receptor antagonists as novel analgesics.     

Oxytocin innervation of spinal preganglionic neurons projecting to the superior cervical ganglion in the rat

The paraventricular nucleus of the hypothalamus is a major integrative nucleus for relaying information from the suprachiasmatic nucleus to the autonomic system. The precise pathway by which this information can influence autonomic functions, such as melatonin synthesis in the pineal gland, is not clear. In the present study, we used a retrograde tracer injected in the superior cervical ganglion to identify spinal preganglionic neurons. One of the main neurotransmitters present in descending projections of the paraventricular nucleus of the hypothalamus, oxytocin, was detected with immunocytochemistry to visualise possible contacts with the neurons located in the intermediolateral column of the spinal cord and projecting to the superior cervical ganglion. Although many appositions could be seen at the light-microscopic level, this abundance could not be confirmed at the electron-microscopic level. The implications of these observations for the overall timing message received by the spinal preganglionic neurons are discussed.     

Increases in vocalization and motor reflex thresholds are influenced by the site of morphine microinjection: Comparisons following administration into the periaqueductal gray, ventral medulla, and spinal subarachnoid space.

The relative influence of morphine microinjected into the periaqueductal gray, ventral medulla (nucleus raphe magnus or nucleus reticularis gigantocellularis), or spinal subarachnoid space on the thresholds of responses organized at spinal (spinal motor reflexes, SMRs), medullary (vocalizations elicited during shock, VDSs), and rhinencephalic-diencephalic (vocalization afterdischarges, VADs) levels of the neuraxis was assessed. Dose-dependent increases in response thresholds differed with the site of morphine injection. These results indicate that μ opiate receptor-linked systems in the mesencephalon, medulla, and spinal cord exert differential antinociceptive effects on pain behaviors organized at different levels of the neuraxis. A hypothesis is offered regarding the mechanisms through which morphine inhibits nociceptive transmission through various levels of the CNS. VADs are promoted as a model system for analyzing the affective-motivational dimension of the pain experience. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Barosensitive neurons in the rostral ventrolateral medulla of the rat in vivo: morphological properties and relationship to C1 adrenergic neurons

The aim of this study, conducted in anaesthetized rats, was to examine the morphology of barosensitive neurons in the rostral ventrolateral medulla and their immunoreactivity for a catecholamine synthesizing enzyme, tyrosine hydroxylase. Thirty neurons displaying inhibitory postsynaptic potentials following stimulation of the aortic depressor nerve were intracellularly labelled with Lucifer Yellow or Neurobiotin. Some of these neurons could be excited antidromically from the second thoracic segment of the spinal cord, with conduction velocities of spinal axons ranging from 1.9 to 7.2 m/s. The filled somas were found immediately caudal to the facial nucleus and ventral or ventromedial to compact formation of the nucleus ambiguus. Some dendrites reached the ventral medullary surface. Axons usually projected dorsomedially and then made a sharp rostral and/or caudal turn. The caudally projecting axon could, in some cases, be followed to the first cervical segment of the spinal cord. Seven cells issued fine axon collaterals on the ipsilateral side. These were identified mainly in two areas: in the rostral ventrolateral medulla (or immediately dorsomedial to that region), and within the dorsal vagal complex. Seven of 27 examined cells (26%) were tyrosine hydroxylase-immunoreactive and were classified as C1 adrenergic neurons. No clear relationship was found between the presence or absence of adrenergic phenotype and the morphology of filled cells. However, the amplitude of aortic nerve-evoked inhibitory postsynaptic potentials was significantly larger in tyrosine hydroxylase-positive neurons. Possible reasons for the low percentage of barosensitive cells with tyrosine hydroxylase immunoreactivity found in this study, in comparison with previously published estimates, are discussed. This is the first study describing the morphology of neurons in this part of the medulla identified as barosensitive in vivo, and directly demonstrating adrenergic phenotype in a subset of these neurons.     

Nociceptive c-fos expression in supraspinal areas in avoidance of descending suppression at the spinal relay station

The number and distribution of Fos-like-immunoreactive neurons in different supraspinal brain areas induced by formalin injection into one hindpaw was estimated in rats with transected dorsal half of the spinal cord at the thoracic level in an attempt to avoid most of the descending modulatory actions. The results showed that: (i) after spinal lesion, the peripheral noxious inputs, going up mainly through the ventral spinal cord, elicited a more widespread and densely located Fos-like-immunoreactive neurons in subcortical areas, many of them showed no Fos expression when noxious stimulation was given in rats with intact spinal cord; (ii) at the same time, a small number of subcortical areas, such as the lateral ventroposterior thalamic nucleus and dorsal raphe nucleus, exhibited no significant increase of nociceptive Fos-like immunoreactive neurons after spinal lesion as compared to that with intact spinal cord; and (iii) there appeared a prominent expansion of cortical areas with densely located Fos-like-immunoreactive neurons in spinal-lesioned rats as compared with the limited labelled areas in the control group with intact spinal cord. These results indicate that: (i) in avoiding the spinally descending modulatory mechanisms, more widespread supraspinal and cortical neurons will be recruited and activated in response to the noxious stimulation; and (ii) the descending systems exert differential actions on the spinal targets which project nociceptive signals to different supraspinal regions. The implication of these facts is discussed.     

TIMP1 and adverse prognosis in non-small cell lung cancer

Antisera were developed that specifically recognize orphanin FQ/nociceptin, the 17 amino acid peptide reported to be the endogenous ligand for the orphan opioid receptor. Immunocytochemical localizations in rat spinal cord demonstrated that orphanin FQ /nociceptin-immunoreactivity (-ir) was abundant in superficial dorsal horn, lateral spinal nucleus and the region dorsal to the central canal, areas that also exhibit prominent enkephalin-and dynorphin-ir. Orphanin FQ/nociceptin-ir was not affected by dorsal rhizotomy, indicating that in spinal cord the peptide is produced by central rather than primary afferent neurons. thus, the distribution of orphanin FQ/nociceptin-ir appeared in neuronal circuits that parallel those containing enkephalin- and dynorphin-ir, with only modest co-existence of these peptides.     

Alpha1-adrenergic receptors in human spinal cord: specific localized expression of mRNA encoding alpha1-adrenergic receptor subtypes at four distinct levels

alpha1-Adrenergic receptors (alpha1ARs) are important in lower urinary tract syndromes such as benign prostatic hypertrophy and bladder irritability. Spinal cord alpha1ARs have been postulated to play a role in modulating these diseases, yet alpha1AR subtype (alpha1a, alpha1b, alpha1d) neuronal localization in human spinal cord has not been described. We therefore tested the hypothesis that alpha1AR subtype distribution varies according to specific spinal cord tract and level. In situ hybridization was performed to identify cell bodies containing alpha1AR subtype mRNA at four levels of human spinal cord (cervical enlargement, thoracic, lumbar, sacral). alpha1AR mRNA is present in ventral gray matter only (ventral>dorsal; sacral>lumbar=thoracic>cervical). Signaling cell bodies were detected in anterior horn motor neurons at all levels; dorsal nucleus of Clarke and intermediolateral columns in cervical enlargement, thoracic and lumbar spinal cord regions; and parasympathetic nucleus in sacral spinal cord. Although all three alpha1AR subtypes are present throughout human spinal cord, alpha1d mRNA predominates overall. If confirmed at a protein level, these findings may contribute to the development of new therapeutic strategies in the treatment of several human diseases.     

Physiologic basis of pulmonary edema during intestinal reperfusion

The ventrolateral portion of the intermediate reticular formation of the medulla (ventrolateral medulla, VLM), including the C1/A1 groups of catecholaminergic neurons, is thought to be involved in control of sympathetic cardiovascular outflow, cardiorespiratory interactions, and reflex control of vasopressin release. As all these functions are affected in patients with multiple systems atrophy (MSA) with autonomic failure, we sought to test the hypothesis that catecholaminergic (tyrosine hydroxylase [TH]-positive) neurons of the VLM are depleted in these patients. Medullas were obtained at autopsy from 4 patients with MSA with prominent autonomic failure and 5 patients with no neurological disease. Patients with MSA had laboratory evidence of severe adrenergic sudomotor and cardiovagal failure. Tissue was immersion fixed in 2% paraformaldehyde at 4 degrees C for 24 hours and cut into 1-cm blocks in the coronal plane from throughout the medulla. Serial 50-microm sections were collected and one section every 300 microm was stained for TH. There was a pronounced depletion of TH neurons in the rostral VLM in all cases of MSA. There was also significant reduction of TH neurons in the caudal VLM in 3 MSA patients compared with 3 control subjects. In 2 MSA cases and in 2 control subjects, the thoracic spinal cord was available for study. There was also depletion of TH fibers and sympathetic preganglionic neurons (SPNs) in the 2 MSA cases examined. Thus, depletion of catecholaminergic neurons in the VLM may provide a substrate for some of the autonomic and endocrine manifestations of MSA.     

Effects of tamoxifen on the cytology of the uterine cervix in breast cancer patients

Knowledge about the central innervation of the lower urinary tract is limited. The spinal cord and the pontine micturition center have been investigated most thoroughly, whereas high centers have received little attention. Pseudorabies virus (PRV), a self-amplifying and transneuronal tracer was injected into the bladder trigone of 21 Sprague-Dawley rats. The animals were killed after 72, 96, and 120 h. The whole CNS was sectioned and immunostained for PRV. CNS centers directly connected to the bladder include the intermedio lateral cell column, the central autonomic nucleus, and the nucleus intercalatus at the spinal cord levels T12-L2 and L6-S2. The raphe pallidus et magnus, the A5 nor-adrenergic area, the pontine micturition center, the locus coeruleus, the periaquaductal gray, the nucleus para- et periventricularis of the hypothalamus, the red nucleus, the medial preoptic area, and the cortex are supraspinal centers connected to the bladder. Lower urinary tract function is a complex multilevel and multineuronal interaction. It involves facilitation and inhibition at many levels of the CNS.     

Evidence for a periaqueductal gray-nucleus retroambiguus-spinal cord pathway in the rat

The nucleus retroambiguus in the cat has been shown to receive strong projections from the periaqueductal gray and to send fibres to distinct motoneuronal cell groups in brainstem and spinal cord. The nucleus retroambiguus plays a role in the production of vocalization and possibly copulatory (lordosis and mounting) behaviour. The question arises of whether a periaqueductal gray nucleus retroambiguus-spinal cord projection also exists in the rat. In the present study, using the retrograde wheatgerm agglutinin-horseradish peroxidase tracing technique, the nucleus retroambiguus was defined as the area in the caudal medulla oblongata (1.0-2.0 mm caudal to the obex) which sends its fibres mainly through the contralateral spinal cord. Further retrograde tracing experiments demonstrated that a relatively large number of neurons in the lateral and ventral periaqueductal gray and immediately adjacent tegmentum projects to the caudal medullary lateral tegmentum. Anterograde wheatgerm agglutinin-horseradish peroxidase tracing studies finally showed that neurons in the lateral periaqueductal gray and immediately adjoining tegmentum project specifically to the nucleus retroambiguus and not to the lateral tegmentum in general, which seems to be the case for the neurons in the ventral periaqueductal gray. The results indicate that in the rat a periaqueductal gray nucleus retroambiguus spinal cord projection also exists, which may be of crucial importance for the study of the anatomical and physiological framework of respiration, vocalization, and female and male reproductive behaviour in this animal.