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A D Loewy

Publications and source records attributed to A D Loewy.

At least 19 recordsLinked to original sources

Periaqueductal gray matter projection to the parabrachial nucleus in rat.

The efferent projections from the periaqueductal gray matter (PAG) to the parabrachial nucleus (PB) were studied in the rat following microinjections of the anterograde axonal tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into restricted regions of the PAG. The dorsomedial and dorsolateral PAG columns project almost exclusively to the superior lateral PB subnucleus, whereas the lateral and ventrolateral PAG columns project to five lateral PB sites: dorsal lateral subnucleus, medial and lateral crescent areas (which flank the dorsal lateral PB subnucleus), central lateral subnucleus (rostral portion), and superior lateral subnucleus. The PAG region lying near the cerebral aqueduct projects to five lateral PB sites: external lateral subnucleus (inner subdivision), medial and lateral crescent areas, central lateral subnucleus (rostral portion), and dorsal lateral subnucleus. The internal lateral PB subnucleus, which projects exclusively to the intralaminar thalamic nuclei, and the Kölliker-Fuse nucleus were not innervated by the PAG. The PAG selectively innervates individual PB subnuclei that may be part of the spino-parachio-forebrain pathway. All PAG columns, including the aqueductal region, project to the superior lateral PB subnucleus, a presumed nociceptive relay site that receives inputs from multiple spinal cord regions (laminae I, V, and VIII) and projects to the ventromedial and retrochiasmatic hypothalamic areas-two regions that have been implicated in complex goal-directed behavior (e.g., food intake and reproductive function). Earlier studies demonstrated that the dorsal lateral and external lateral PB subnuclei (inner division) receive overlapping inputs from the superficial dorsal horn (laminae I and II) and the nucleus tractus solitarius, and both PB subnuclei send projections to limbic forebrain areas (e.g., hypothalamus, preoptic region, amygdala). Because the PAG projects to both of these PB subnuclei, this projection system possibly functions as a behavioral state-dependent filter system that modulates ascending nociceptive and/or visceral information as it is relayed through the PB to forebrain sites.

Amygdala

Periaqueductal gray matter input to cardiac-related sympathetic premotor neurons.

The periaqueductal gray matter (PAG) serves as the midbrain link between forebrain emotional processing systems and motor pathways used in the defense reaction. Part of this response depends upon PAG efferent pathways that modulate cardiovascular-related sympathetic outflow systems, including those that regulate the heart. While it is known that the PAG projects to vagal preganglionic neurons, including possibly cardiovagal motoneurons, no information exists on the PAG circuits that may affect sympathetically mediated cardiac functions and, thus, the purpose of this study was to use neuroanatomical methods to identify these pathways. First, viral transneuronal retrograde tracing experiments were performed in which pseudorabies virus (PRV) was injected into the stellate ganglion of rats. After 4 days survival, five PAG regions contained transynaptically infected neurons; these included the dorsomedial, lateral and ventrolateral PAG columns as well as the Edinger-Westphal and precommissural nuclei. Second, the descending efferent PAG projections were studied with the anterograde axonal marker Phaseolus vulgaris leuco-agglutinin (PHA-L) with a particular focus on determining whether the PAG projects to the intermediolateral cell column (IML). Almost no axonal labeling was found throughout the thoracic IML suggesting that the PAG modulates sympathetic functions by indirect pathways involving synaptic relays through sympathetic premotor cell groups, especially those found in the medulla oblongata. This possibility was examined by a double tracing study. PHA-L was first injected into either the lateral or ventrolateral PAG and after 6 days, PRV was injected into the ipsilateral stellate ganglion. After an additional 4 days survival, a double immunohistochemical procedure for co-visualization of PRV and PHA-L was used to identify the sympathetic premotor regions that receive an input from the PAG. The PAG innervated specific groups of sympathetic premotor neurons in the hypothalamus, pons, and medulla as well as providing reciprocal intercolumnar connections within the PAG itself (Jansen et al., Brain Res. 784 (1998) 329-336). The major route terminates in the ventral medulla, especially within the medial region which contains sympathetic premotor neurons lying within the raphe magnus and gigantocellular reticular nucleus, pars alpha. Both serotonergic and non-serotonergic sympathetic premotor neurons in these two regions receive inputs from the PAG. Weak PAG projections to sympathetic premotor neurons were found in the rostral ventrolateral medulla (including to C1 adrenergic neurons), locus coeruleus, A5 cell group, paraventricular and lateral hypothalamic nuclei. In summary, both the lateral and ventrolateral PAG columns appear to be capable of modulating cardiac sympathetic functions via a series of indirect pathways involving sympathetic premotor neurons found in selected sites in the hypothalamus, midbrain, pons, and medulla oblongata, with the major outflow terminating in bulbospinal regions of the rostral ventromedial medulla.

Animals

CNS cell groups projecting to sympathetic outflow of tail artery: neural circuits involved in heat loss in the rat.

In the rat, approximately 20% of total body heat-loss occurs by sympathetically mediated increases in blood flow through an elaborate system of arteriovenous anastomoses in the skin of its tail. In this study, the CNS cell groups that regulate this sympathetic outflow were identified by the viral transneuronal labeling method. Pseudorabies virus was injected into the wall of the ventral tail artery in rats that had their cauda equina transected to eliminate the somatic innervation of the tail. After 4-7 days survival, the pattern of CNS transneuronal labeling was studied. Sympathetic preganglionic neurons in the T11-L2 (mainly L1) levels of the intermediolateral cell column (IML) were labeled by 4 days. After 5 days, sympathetic pre-motor neurons (i.e., supraspinal neurons that project to the IML) were identified near the ventral medullary surface; some of these contained serotonin immunoreactivity. Additional groups of the sympathetic premotor areas were labeled by 6 days post-injection, including the rostral ventrolateral medulla (C1 adrenergic neurons), rostral ventromedial medulla, caudal raphe nuclei (serotonin neurons in the raphe pallidus and magnus nuclei), A5 noradrenergic cell group, lateral hypothalamic area and paraventricular hypothalamic area (oxytocin-immunoreactive neurons). Seven days after the PRV injections, additional cell groups in the telencephalon (viz., bed nucleus of the stria terminalis, medial and lateral preoptic areas and medial preoptic nucleus), diencephalon (viz., subincertal nucleus, zona incerta as well as dorsal, dorsomedial, parafascicular, posterior and ventromedial hypothalamic nuclei) and midbrain (viz., periaqueductal gray matter, precommissural nucleus, Edinger-Westphal nucleus and ventral tegmental area) were labeled. The discussion is focused on the CNS cell groups involved in the control of body temperature and fever.

Animals

Local connections between the columns of the periaqueductal gray matter: a case for intrinsic neuromodulation.

Chemical stimulation of the lateral or ventrolateral columns of the midbrain periaqueductal gray matter (PAG) in conscious animals produces opposite responses (viz., defensive behavior and pressor responses from the lateral column vs. quiescence and depressor responses from the ventrolateral column), raising the possibility that the two columns are interconnected. To test this hypothesis, two types of anatomical experiments were performed in rats. First, the anterograde axonal marker Phaseolus vulgaris leuco-agglutinin (PHA-L) was injected into individual PAG columns or adjoining regions which included the Edinger-Westphal, dorsal raphe, and precommissural nuclei. The results shows that each column projects bilaterally to all of the other PAG columns, and also provides local connections within its own column. Furthermore, the Edinger-Westphal and precommissural nuclei project to all four PAG columns, while the dorsal raphe nucleus projects only to the ventrolateral and lateral columns. In a second experiment, we found that cardiovascular-related PAG projection neurons of both the lateral and ventrolateral columns receive an input from the reciprocal PAG column. This was demonstrated by a double tracer neuroanatomical study in which PHA-L was first iontophoretically ejected into either the lateral or ventrolateral PAG columns and then, several days later the retrograde transneuronal viral tracer, pseudorabies virus, was injected into the stellate sympathetic ganglion. Intra-PAG circuits were visualized by a dual immunohistochemical procedure. These results suggest that during the fight-or-flight response when the 'fight' program is activated, inhibition of the 'flight' PAG network may occur and the converse situation may occur during the flight response.

Animals

Viruses as transneuronal tracers for defining neural circuits.

Live viruses can be used as tools to label chains of neurons and thus to define functionally connected CNS circuits. This review summarizes the background and general principles involved in using the viral tracing technology. An attenuated form of a pig herpes virus, known as the Bartha's K strain of pseudorabies virus, has proven to be a useful type of virus for the analysis of CNS systems in the rat. The properties of this virus and the evidence for its specificity in causing trans-synaptic infections is discussed.

Animals

CNS sites involved in sympathetic and parasympathetic control of the pancreas: a viral tracing study.

The viral transneuronal tracing method was used to identify the CNS cell groups that regulate the parasympathetic and sympathetic outflow systems of the pancreas. Pseudorabies virus (PRV) was injected into the pancreas of vagotomized rats and after 6 days survival, the pattern of transneuronal labeling in the CNS sympathetic regulatory regions was determined. The converse experiment was performed in order to elucidate the central parasympathetic cell groups that regulate the pancreas. Immunohistochemical methods were used to identify putative neuropeptide- and catecholamine-containing CNS neurons involved in these regulatory circuits. The major finding of this study indicates that five brain regions, viz., paraventricular hypothalamic nucleus, perifornical hypothalamic region, A5 catecholamine cell group, rostral ventrolateral medulla, and lateral paragigantocellular reticular nucleus, contain a considerable amount of overlap in cell body labeling. In addition, the ventrolateral part of the periaqueductal gray matter and gigantocellular reticular nucleus, ventral part also showed a similar overlap, but the numbers of neurons found in these areas were considerably lower than the five major regions. These data suggest that these brain regions may provide parallel and possibly redundant, autonomic pathways affecting glucagon and adrenaline release.

Adrenal Medulla

Periaqueductal gray matter projection to vagal preganglionic neurons and the nucleus tractus solitarius.

The periaqueductal gray matter (PAG) has been implicated in a variety of different functions, including autonomic regulation. Chemical stimulation of the lateral PAG produces hypertension and tachycardia while activation of the ventrolateral PAG produces the opposite effect. While these effects are the result of alterations in sympathetic activity, little is known about whether the PAG can modulate vagal functions as well. The anterograde axonal tracing method using the plant lectin Phaseolus vulgaris leucoagglutinin (PHA-L) was used to determine whether both of the lateral and ventrolateral PAG columns project to vagal preganglionic neurons and/or to the nucleus tractus solitarius (NTS). Highly restricted PHA-L injections were made in all four PAG columns throughout their rostrocaudal extent in rats. Labeled fibers were visualized by immunohistochemistry and studied in relationship with choline acetyltransferase (ChAT) immunostained parasympathetic preganglionic neurons of the dorsal motor vagal nucleus (DMV) and nucleus ambiguous (NA). The lateral PAG projects to the lateral DMV and to the caudal part of the external NA. The ventrolateral PAG innervates the same regions and also projects to the rostral part of the external NA -- a site that contains cardiac parasympathetic preganglionic neurons. Both the lateral and ventrolateral PAG project to the NTS in a similar fashion innervating the medial, ventrolateral and commissural subnuclei. In summary, the lateral and ventrolateral PAG have similar patterns of innervation of the NTS and DMV, but their projection to the NA is different: the rostral external NA receives innervation only from the ventrolateral PAG and the lateral PAG innervates the caudal part.

Animals

Neurons lying in the white matter of the upper cervical spinal cord project to the intermediolateral cell column.

Neurons lying in the white matter of the upper cervical spinal cord become transneuronally labelled following pseudorabies virus injections into the kidney or stellate ganglion, suggesting that they project directly to sympathetic preganglionic neurons. In the present study, we extend these findings and report here that i) neurons in both the lateral spinal nucleus and lateral funiculus become transneuronally labelled after pseudorabies virus injections into the superior cervical ganglion, stellate ganglion, celiac ganglion, or adrenal gland and ii) both of these two cell groups project directly to the sympathetic preganglionic neurons as demonstrated with the Phaseolus vulgaris leuco-agglutinin axonal tracing method. In addition, lateral funiculus neurons project to the cervical and upper thoracic dorsal horn (lamina V), intermediate gray matter (laminae VII and X), and ventral horn. The lateral spinal nucleus also projects to the medial part of laminae I and II, V, VII. To verify that pseudorabies virus-infected lateral funiculus and lateral spinal nucleus cells have a neuronal phenotype, we demonstrated that these cells also can be immunostained with antibodies directed against a neuron specific marker, neuronal nuclear protein called NeuN, but not with antibodies against glial acidic fibrillary protein or oligodendroglia. In summary, this report provides the first evidence that two descending sympathetic projection systems arise from neurons lying within the white matter of the cervical spinal cord.

Animals

Central connections of the motor and sensory vagal systems innervating the trachea.

Cholera toxin beta-subunit was used as both a transganglionic and retrograde cell body tracer to determine respectively the central sensory and motor systems innervating the trachea in three mammalian species, dog, ferret and rat. A basic pattern was found in all three animals. Sensory fibers terminated in three subnuclei of the nucleus tractus solitarius (NTS) with the densest concentration localized in a restricted part of the medial part of the rostral NTS. Weaker projections were identified in the ventrolateral NTS subnucleus and sparse labeling was seen in the commissural NTS subnucleus. No labeling was identified in the area postrema. The pattern of retrograde cell-body labeling was also similar in all three species. Two main sites were labeled: the rostralmost part of the dorsal vagal nucleus and the rostral nucleus ambiguus (NA). In the NA, cell labeling was found in mainly in the ventral (or external) portion of the nucleus, but some labeled neurons were consistently found in the compact NA as well. In addition, labeled neurons were also seen in the dorsomedial part of the C1-C2 ventral horn. In summary, the central sites of termination of the sensory fibers and cells of origin innervating the trachea were similar in all three species.

Animals

Central command neurons of the sympathetic nervous system: basis of the fight-or-flight response.

During stress, the activity of the sympathetic nervous system is changed in a global fashion, leading to an increase in cardiovascular function and a release of adrenal catecholamines. This response is thought to be regulated by a common set of brain neurons that provide a dual input to the sympathetic preganglionic neurons regulating cardiac and adrenal medullary functions. By using a double-virus transneuronal labeling technique, the existence of such a set of central autonomic neurons in the hypothalamus and brainstem was demonstrated. These neurons innervate both of the sympathetic outflow systems and likely function in circumstances where parallel sympathetic processing occurs, such as in the fight-or-flight response.

Adrenal Glands

Pseudorabies virus mutants as transneuronal markers.

The transneuronal labeling properties of three genetically engineered forms of the Bartha strain of pseudorabies virus (PRV) were studied in the ocular sympathetic pathway of rats. Bartha PRV mutants in which expression of the viral glycoprotein gI (homologous to gE of herpes simplex virus type 1, HSV-1) was restored (Bartha gI+) or which express a wildtype form of glycoprotein gIII (homologous to gC of HSV-1 and referred here as Bartha gIIIKa) were analyzed. In addition, a Bartha PRV mutant (Bartha beta-gal) containing the lacZ gene encoding E. coli beta-galactosidase inserted into the gX gene (homologous to gG of HSV-1) was also studied. These were compared to the parental strain--Bartha PRV. The pattern of transneuronal labeling in the intermediolateral cell column was studied 4 days after 5 microliters of different concentrations of viral stocks were injected into the anterior chamber of the eye. The optimal infectious dose required to produce the maximal number of cases with specific transneuronal labeling of sympathetic preganglionic neurons was determined and these were as follows: Bartha PRV = 10(7.5) pfu/ml, Bartha beta-galactosidase = 10(6.5) pfu/ml, Bartha gIIIKa = 10(5) pfu/ml, Bartha gI+ = 10(4) pfu/ml. An inverse relationship between specificity and infectivity rate was observed. Bartha beta-gal produced the greatest number of cases with specific labeling (76%); Bartha gI+ produced the lowest level (10%) and thus, this virus is not useful for transneuronal labeling studies. Bartha gIIIKa labeled more sympathetic preganglionic neurons (second-order neurons) than Bartha beta-gal or Bartha PRV. Bartha gIIIKa and Bartha beta-gal viruses labeled more interneurons (third-order) than the standard Bartha PRV.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Transneuronal labeling of CNS neuropeptide and monoamine neurons after pseudorabies virus injections into the stellate ganglion.

The viral transneuronal labeling method was used in combination with immunohistochemical procedures to identify CNS neuropeptide and monoamine neurons that innervate the sympathetic preganglionic neurons (SPNs) which project to the stellate ganglion--the principal source of the sympathetic supply to the heart. Transneuronal labeling was found at three CNS levels: spinal cord, brainstem, and hypothalamus. In the thoracic spinal cord, apart from the pseudorabies virus (PRV)-labeled stellate SPNs, PRV-labeled neurons were localized in laminae I/II, IV, V, VII, and X as well as in the lateral spinal nucleus and lateral funiculus. In the C1-C4 spinal segments, labeled neurons were found in the lateral funiculus as well as laminae V and VII of the spinal gray matter. PRV-labeled cells were identified in lamina V and the dorsolateral funiculus of the lumbar spinal cord. Three medullary areas were consistently labeled: rostral ventromedial medulla (RVMM), rostral ventrolateral medulla (RVLM), and caudal raphe nuclei. The greatest concentration of labeling was found in the RVMM. This projection arose from adrenergic, serotonergic (5-HT), thyrotropin releasing hormone (TRH), substance P, somatostatin, enkephalin, and vasoactive intestinal peptide (VIP) immunoreactive neurons. The RVLM projection originated mainly from C1 adrenergic neurons, some of which contained immunoreactive neuropeptide Y (NPY). C3 adrenergic-NPY neurons lying near the floor of the 4th ventricle were also labeled. Enkephalin-, somatostatin- and VIP-immunoreactive RVLM neurons also contributed to this projection. 5-HT neurons of the caudal raphe nuclei (raphe pallidus, raphe obscurus, and raphe magnus) were labeled; some of these contained substance P or TRH-immunoreactivity with an occasional neuron staining for all three putative neurotransmitters. In the pons, catecholamine neurons in the A5 cell group, subcoeruleus and Kolliker-Fuse nuclei were labeled. The midbrain contained relatively few infected cells, but some were present in the Edinger-Westphal and precommissural nuclei. Forebrain labeling was concentrated in the paraventricular hypothalamic nucleus (PVN) with lesser amounts in the lateral hypothalamic area (LHA) and the perifornical region. In the PVN, oxytocin-immunoreactive neurons accounted for the greatest chemically-defined projection while corticotrophin releasing factor (CRF), vasopressin-, and angiotensin II-immunoreactive neurons provided successively lesser inputs. In the LHA, angiotensin II-immunoreactive neurons were labeled. In summary, this study provides the first detailed map of the chemically-coded CNS neurons involved in the control of the cardiosympathetic outflow.

Animals

Whole-cell recordings from visualized C1 adrenergic bulbospinal neurons: ionic mechanisms underlying vasomotor tone.

The membrane properties of visually identified, DiI retrogradely labeled bulbospinal neurons of the C1 adrenergic cell group were studied by whole-cell recordings in brainstem slices from 7- to 10-day-old rats. A post-hoc histochemical analysis allowed us to evaluate the electrophysiological properties of the C1 adrenergic neurons, a group of cells known to project to the sympathetic preganglionic neurons. Two types of cells were labeled: pacemaker and non-pacemaker neurons. In voltage-clamp mode, C1 pacemaker neurons exhibited a TTX-sensitive, persistent inward current that was activated between -55 and -50 mV and reached a peak between -40 and -30 mV. This current was significantly larger in the pacemaker neurons as compared to the non-pacemaker neurons and appeared to be a principal conductance driving the C1 pacemaker activity. Two other conductances modulated the frequency of pacemaker discharge: (1) an anomalous rectifier accelerated pacemaker frequency by three synergistic actions: (a) depolarizing it at rest, (b) increasing the slope of the pacemaker potentials, and (c) limiting hyperpolarizing membrane excursions; and (2) an A-type current which had two opposing actions: (a) slowing it by decreasing the slope of the pacemaker potential, and (b) accelerating it by repolarizing the fast action potential. Persistent sodium current functions as the driver potential responsible for the tonic firing pattern of the C1 bulbospinal neurons providing a cellular mechanism responsible for the descending excitatory drive imposed onto sympathetic preganglionic neurons. Thus, it may explain how C1 neurons may function to maintain vasomotor tone or modulate other autonomic functions. This study is the first attempt to analyze voltage-activated membrane conductances of RVLM neurons of known phenotype and axonal connections.

Action Potentials

Whole-cell patch-clamp recordings from visualized bulbospinal neurons in the brainstem slices.

The purpose of this study was to develop a method for electrophysiological characterization of retrogradely labeled bulbospinal neurons in the specific cytoarchitectonic regions in the brainstem slices. Several days after the spinal cord was injected with the carbocyanine dye, DiI, retrogradely labeled bulbospinal neurons were visualized by epifluorescence optics in the brainstem slices with the aid of a silicon intensifier tube (SIT) camera. Labeled somata were routinely seen in the caudal raphe nuclei, rostroventral medial and lateral portions of the medulla, the A5 group and in other medullary sites known to project to the spinal cord. Electrophysiological properties of the DiI-labeled neurons were assessed by whole-cell recordings using micropipettes filled with biocytin. The slices were subsequently processed for dual visualization of biocytin and serotonin or a marker for noradrenergic neurons, tyrosine hydroxylase (TH). The electrophysiological properties of bulbospinal neurons were correlated with their morphology and neurochemical content. This technique may be useful in other areas of CNS for studying morphology, neurochemical content and physiology of retrogradely labeled neurons.

Animals

CNS monoamine cell groups projecting to pancreatic vagal motor neurons: a transneuronal labeling study using pseudorabies virus.

The CNS monoamine cell groups that project to the pancreatic parasympathetic preganglionic neurons were identified with the use of the viral retrograde transneuronal labeling method. Pseudorabies virus (PRV) was injected into the pancreas of C8 spinal rats and subsequently, transneuronally-labelled central monoamine neurons were mapped in brain tissue sections that had been stained by an immunohistochemical procedure that allowed for the visualization of PRV products and biogenic amine neurotransmitter enzymes or serotonin (5-HT) in the same neuron. The enzymes studied were tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), phenylethanolamine-N-methyltransferase (PNMT), and histidine decarboxylase. Pancreatic vagal motor neurons originate exclusively from the dorsal vagal motor nucleus and some of these may be dopamine neurons because they were TH immunopositive, but DBH and PNMT immunonegative. Transneuronally labeled aminergic neurons were found throughout the medulla oblongata. The adrenergic inputs arose from the C1, C2, and C3 cell groups. Noradrenergic inputs originated predominantly from the A5 cell group, with lesser contributions from the A1 and A2 cell groups as well as from the area postrema. None of the other CNS catecholamine cells were labeled, except for some weakly staining TH-immunoreactive neurons, presumably dopaminergic, in the paraventricular hypothalamic nucleus (PVN). The greatest number of 5-HT neurons that innervate the pancreatic vagal motor neurons come from the gigantocellular reticular nucleus, pars alpha with lesser inputs from the raphe magnus, obscurus, and pallidus nuclei. None of the CNS histaminergic cell groups were labeled.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

CNS cell groups projecting to pancreatic parasympathetic preganglionic neurons.

The CNS cell groups that project to the pancreatic parasympathetic preganglionic neurons were identified by the viral retrograde transneuronal labeling method. Pseudorabies virus (PRV) was injected into the pancreas of C8 spinal rats and after 6 days survival, the animals were perfused and their brains processed for immunohistochemical detection of PRV. Parasympathetic preganglionic neurons of the dorsal vagal nucleus were retrogradely labeled with PRV. Several CNS cell groups consistently contained transneuronally labeled neurons. In the medulla oblongata, labeled neurons were found in the nucleus tractus solitarius, area postrema, paratrigeminal nucleus, lateral paragigantocellular reticular nucleus, raphe pallidus and obscurus nuclei, C3 region and scattered cells in the ventral medullary reticular formation. In the pons, the A5 cell group, Barrington's nucleus and the subcoeruleus region contained labeled neurons. Only an occasional labeled cell was identified in the parabrachial nucleus. In the midbrain, almost no labeling was found except for an occasional neuron in the central gray matter. In the diencephalon, labeling was found in the paraventricular hypothalamic nucleus (PVN) as well as in the lateral hypothalamic nucleus at two levels (one at the level of the PVN and the other at the level of the subthalamic nucleus). In addition, the perifornical and dorsal hypothalamic nuclei contained labeled neurons. A few cells were found in the peripheral part of the dorsomedial hypothalamic nucleus. No labeling was seen in the ventromedial hypothalamic nucleus. In the telencephalon, the central amygdaloid nucleus and the bed nucleus of the stria terminalis were labeled.

Animals

CNS innervation of airway-related parasympathetic preganglionic neurons: a transneuronal labeling study using pseudorabies virus.

The CNS cell groups that innervate the tracheal parasympathetic preganglionic neurons were identified by the viral retrograde transneuronal labeling method. Pseudorabies virus (PRV) was injected into the tracheal wall of C8 spinal rats and after 4 days survival, brain tissue sections from these animals were processed for immunohistochemical detection of PRV. Retrogradely labeled parasympathetic preganglionic neurons were seen in three sites in the medulla: the compact portion of the nucleus ambiguus, the area ventral to the nucleus ambiguus, and the rostralmost portion of the medial nucleus tractus solitarius (NTS); this labeling pattern correlated well with the retrograde cell body labeling seen following cholera toxin beta-subunit injections in the tracheal wall. PRV transneuronally labeled neurons were found throughout the CNS with the most abundant labeling concentrated in the ventral medulla oblongata. Labeled neurons were identified along the ventral medullary surface, and in nearby areas including the parapyramidal, retrotrapezoid, gigantocellular and lateral paragigantocellular reticular nuclei as well as the caudal raphe nuclei (raphe pallidus, obscurus, and magnus). Serotonin (5-HT) neurons of the caudal raphe complex (B1-B3 cell groups) and ventromedial medulla were labeled as well as a few C1 adrenergic neurons. The A5 cell group was the major noradrenergic area labeled although a small number of locus coeruleus neurons were also labeled. Several NTS regions contained labeled cells including the commissural, intermediate, medial, central, ventral, and ventrolateral subnuclei. PRV infected neurons were present in the Kölliker-Fuse and Barrington's nuclei. In the rostral mesencephalon, the precommissural nucleus of the dorsal periventricular gray matter was labeled. Labeling was present in the dorsal, lateral and paraventricular hypothalamic nuclei. In summary, the airway parasympathetic preganglionic neurons are innervated predominantly by a network of lower brainstem neurons that lie in the same regions known to be involved in respiratory and cardiovascular regulation. These findings are discussed in relationship to some of the potential CNS mechanisms that may be operative in airway disorders as well as potentially involved in certain fatal respiratory conditions such as Ondine's curse and sudden infant death syndrome (SIDS).

Animals