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Biomedical subjects

C B Saper

Publications and source records attributed to C B Saper.

At least 109 records · Page 6Linked to original sources

Opioid antagonist diprenorphine microinjected into parabrachial nucleus selectively inhibits vasopressin response to hypovolemic stimuli in the rat.

Subcutaneous injection of the potent, nonselective opioid antagonist diprenorphine inhibits the vasopressin response to acute hypovolemia. To determine if this inhibition is due to antagonism of opioid receptors in brain pathways that mediate volume control, we determined the vasopressin response to different stimuli when diprenorphine or other opiates were injected into the cerebral ventricles, the nucleus tractus solitarius (NTS), or the lateral parabrachial nucleus (PBN) of rats. We found that the vasopressin response to hypovolemia was inhibited by injection of diprenorphine into the cerebral ventricles at a dose too low to be effective when given subcutaneously. This response also was inhibited when a 20-fold lower dose of diprenorphine was injected into the PBN but not when it was injected into the NTS. The inhibitory effect of diprenorphine in the PBN was not attributable to a decrease in osmotic or hypovolemic stimulation and did not occur with osmotic or hypotensive stimuli. Injecting the PBN with equimolar doses of the mu antagonist naloxone, the delta antagonist ICI-154,129 or the kappa-1 agonist U-50,488H had no effect on basal or volume-stimulated vasopressin. We conclude that the inhibition of vasopressin by diprenorphine is due partially to action at a novel class of opioid receptors that transmit volume stimuli through the PBN.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Topographic organization of cardiovascular responses to electrical and glutamate microstimulation of the parabrachial nucleus in the rat.

We examined the functional organization of the parabrachial complex (PB) by mapping the cardiovascular and respiratory responses to PB microstimulation in anesthetized rats. The PB was explored with 100 microns resolution, at threshold doses of electrical current (5 microA) and glutamate (10-500 pmols), and the locations of stimulation sites were identified by small iontophoretic or pressure injections of biocytin or Phaseolus vulgaris leucoagglutinin. Threshold doses of either L-glutamate or electrical current pulses caused pressor-tachycardic responses that mapped to the outer edge of the external lateral subnucleus while depressor bradycardic responses were elicited from stimuli near the dorsal lateral subnucleus. Pressor responses persisted in paralyzed, ventilated animals and were thus not dependent upon concomitant respiratory changes. Cardiac arrhythmias sometimes occurred during large pressor responses and during augmented breaths that occurred during or following PB stimulation. These observations indicate that the PB contains at least two distinct neuronal systems that are potently and opposingly involved in cardiovascular control. The locations of the sites giving the most potent responses implicate specific ascending and descending pathways as substrates for the cardiovascular responses.

Animals↗

Cloning of a novel somatostatin receptor, SSTR3, coupled to adenylylcyclase.

The gene encoding a novel mouse somatostatin receptor termed mSSTR3 was isolated and characterized. The sequence of mSSTR3 shows 46 and 47% identity with mSSTR1 and mSSTR2, respectively. mSSTR3 binds somatostatin-14 and somatostatin-28 with high affinity, but shows very low affinity for the somatostatin analogs MK-678 and SMS-201-995. In addition, mSSTR3 is coupled to pertussis toxin-sensitive G proteins and mediates somatostatin inhibition of forskolin-stimulated and dopamine D1 receptor-stimulated cAMP formation, indicating that it is coupled to adenylylcyclase. The pharmacological properties of mSSTR3 and its ability to couple with adenylylcyclase distinguish SSTR3 from the other cloned somatostatin receptors and indicates that it mediates biological functions different from SSTR1 or SSTR2. In situ hybridization indicates that SSTR3 mRNA is widely distributed in the mouse brain, and its expression in the nucleus of the lateral olfactory tract and in the piriform cortex, the primary olfactory cortex in the rodent brain, suggests that SSTR3 may participate in the processing and modulation of primary sensory information.

Adenylyl Cyclases↗

Distribution and characterization of cyclooxygenase immunoreactivity in the ovine brain.

Evidence from tissue culture studies suggests that glial cells are the principal source of prostaglandins in the brain. We have used immunohistochemistry, Western blot analysis, and enzyme activity assays to localize cyclooxygenase (COX), the enzyme responsible for the conversion of arachidonic acid to prostaglandins, in situ in the normal ovine brain. We observed very few immunoreactive glial cells. In contrast, an extensive distribution of COX-like immunoreactive (ir) neuronal cell bodies and dendrites and a corresponding pattern of COX enzyme activity were observed. COXir neurons were most abundant in forebrain sites involved in complex, integrative functions and autonomic regulation such as the cerebral cortex, hippocampus, amygdala, bed nucleus of the stria terminalis, substantia innominata, dorsomedial nucleus of the hypothalamus, and tuberomammillary nucleus. Moderate populations were observed in other regions of the central nervous system implicated in sensory afferent processing, including the dorsal column nuclei, spinal trigeminal nucleus, and superior colliculus, and in structures involved in autonomic regulation, such as the nucleus of the solitary tract, parabrachial nucleus, and the periaqueductal gray matter. We did not observe COXir axons or terminal fields, however. Our results suggest that neurons may use prostaglandins as intracellular or perhaps paracrine, but probably not synaptic, mediators in the normal brain.

Acetylcholinesterase↗

Organization of medullary adrenergic and noradrenergic projections to the periaqueductal gray matter in the rat.

The periaqueductal or midbrain central gray matter (CG) in the rat contains a dense network of adrenergic and noradrenergic fibers. We examined the origin of this innervation by using retrograde and anterograde axonal tracers combined with immunohistochemistry for the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT). Following injections of the fluorescent tracers Fast Blue or Fluorogold into the CG, double-labeled neurons in the medulla were identified mainly in the noradrenergic A1 group in the caudal ventrolateral medulla (VLM) and A2 group in the medial part of the nucleus of the solitary tract (NTS); and in the adrenergic C1 group in the rostral ventrolateral medulla and C3 group in the rostral dorsomedial medulla. Injections of Phaseolus vulgaris-leucoagglutinin (PHA-L) into these cell groups resulted in a distinct pattern of axonal labeling in various subdivisions of the CG. Anterogradely labeled fibers originating in the medial NTS were predominantly found in the lateral portion of the dorsal raphe nucleus and in the adjacent part of the lateroventral CG (CGlv). Following PHA-L injections into the C3 region the anterogradely labeled fibers were diffusely distributed in the CGlv and the dorsal raphe nucleus at caudal levels, but rostrally tended to be located laterally in the CGlv. In contrast, ascending fibers from the caudal and rostral VLM terminated in the rostral dorsal part of the CGlv and in the dorsal nucleus of the CG, whereas ventral parts of the CG, including the dorsal raphe nucleus, contained few afferent fibers. Double-label studies with antisera against DBH and PNMT confirmed that noradrenergic neurons in the A1 and A2 groups and adrenergic neurons in the C1 and C3 groups contributed to these innervation patterns in the CGlv. Noradrenergic and adrenergic projections from the medulla to the CG may play an important role in a variety of autonomic, sensory and behavioral processes.

Adrenergic Fibers↗

Endogenous pyrogens in the CNS: role in the febrile response.

The febrile reaction is an integrated endocrine, autonomic and behavioral response, coordinated by the hypothalamus, that includes certain components of the stress response, such as elevated corticosteroid secretion. It is produced by the actions of circulating cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF), on the organum vasculosum of the lamina terminalis (OVLT), resulting in the secretion of prostaglandin E2, which initiates a variety of responses, including elevation of body temperature and corticosteroid secretion. Although circulating cytokines apparently do not enter the brain, injections of IL-1 or TNF well within the blood-brain barrier produce identical effects. We have examined the localization of possible central sources of cytokines and prostaglandins, using immunohistochemistry, immunoblotting and enzyme assay. Our data indicate that in the brain cyclooxygenase, the key enzyme in the synthesis of prostaglandins, is found in neurons in the OVLT, but is also made by neurons in many sensory and visceral regulatory systems. We present evidence also that IL-1 beta in the human brain and TNF alpha in the mouse may be present in the central nervous system as neuromodulators that are important for producing the autonomic, endocrine and behavioral components of the febrile reaction. We propose a sequence of events in the febrile reaction involving: (1) action of circulating cytokines on cyclooxygenase containing neurons within the OVLT to produce local prostaglandin secretion; (2) local diffusion of prostaglandin E2 into the preoptic and anterior hypothalamic areas; (3) action of prostaglandin E2 on cytokine containing neurons in the preoptic and anterior hypothalamic areas; and (4) release of cytokines from neuronal terminals at distal sites involved in producing the autonomic, endocrine and behavioral components of the febrile reaction.

Animals↗

Paraneoplastic cerebellar degeneration. III. Cerebellar degeneration, cancer, and the Lambert-Eaton myasthenic syndrome.

We studied nine patients with a subacute onset of a pancerebellar syndrome. Six had known cancer (three small-cell carcinoma of the lung [SCLC], one metastatic small-cell carcinoma, one small-cell carcinoma of the prostate, and one non-Hodgkin's lymphoma). Six of eight who had neurophysiologic testing, including the three patients without detectable cancer, had coexistent Lambert-Eaton myasthenic syndrome (LEMS). In two of the patients, LEMS was discovered only by neurophysiologic testing. We looked for anti-Purkinje cell autoantibodies in all patient's sera and in four patients' CSF. We also looked for autoantibodies to voltage-gated calcium channels (VGCCs) in seven patients' sera and two patients' CSF, using the 125I-omega-conotoxin radioimmunoassay. We were unable to detect anti-Purkinje cell autoantibodies in any patients' serum or CSF. However, there were raised titers of anti-VGCC autoantibodies in five of seven patients' serum, including one patient with SCLC who did not have LEMS, and in the CSF of one of two patients. We conclude that the frequency of presentation of a pancerebellar syndrome with LEMS is higher than expected by chance and is usually associated with cancer. In some of these patients, LEMS may be clinically occult. The presence of LEMS and raised titers of anti-VGCC autoantibodies in some patients with subacute cerebellar degeneration is suggestive of an autoimmune etiology even though anti-Purkinje cell antibodies could not be detected. Anti-VGCC autoantibodies are not confined to LEMS. They may be found at high titer in CSF as well as serum.

Aged↗

Differential expression of somatostatin receptor subtypes in brain.

The tetradecapeptide somatostatin has been implicated as an important regulator of neuronal and neuroendocrine function in the CNS. The cellular actions of somatostatin are mediated by specific receptors. The genes encoding two different somatostatin receptors (SSTRs) have been isolated and characterized, and RNA blotting studies have shown that both SSTR1 and SSTR2 are expressed in the brain. In order to gain a better understanding of the functions of somatostatin in the CNS, the distribution of SSTR1 and SSTR2 mRNAs was determined using the technique of in situ hybridization. SSTR1 mRNA was present throughout the mouse brain, particularly in the supra- and infragranular layers of the cortex, the amygdala, hippocampus, bed nucleus of the stria terminalis, substantia innominata, hypothalamus, pretectum, substantia nigra, parabrachial nucleus, and nucleus of the solitary tract. SSTR2 mRNA was primarily observed in the infragranular layers of the cortex, the amygdala, claustrum, endopiriform nucleus, arcuate and paraventricular nuclei of the hypothalamus, and medial habenular nucleus. Several regions of the brain reported to contain dense somatostatin-like immunoreactive terminal fields and receptor binding sites were devoid of both SSTR1 and SSTR2 mRNA, suggesting the existence of additional SSTR subtypes.

Animals↗

Organization of visceral and limbic connections in the insular cortex of the rat.

The anterograde and retrograde transport of horseradish peroxidase was used to study the anatomical organization of visceral and limbic terminal fields in the insular cortex. Following injections into the ventroposterolateral parvicellular (VPLpc) and ventroposteromedial parvicellular (VPMpc) visceral relay nuclei of the thalamus, dense anterograde and retrograde labeling was present in the posterior granular and dysgranular insular cortices, respectively. The parabrachial nucleus had extensive connections with the posterior dysgranular cortex and to a lesser degree with the anterior dysgranular and granular cortices. In contrast, injections into the medial prefrontal cortex and mediodorsal nucleus of the thalamus resulted in dense anterograde and retrograde labeling primarily in the anterior agranular cortex, whereas injections in the amygdala resulted in axonal labeling in the agranular and dysgranular insular cortices. Injections into the lateral hypothalamic area resulted in dense anterograde and retrograde labeling mainly in the agranular and dysgranular cortices and moderate to light labeling in the granular cortex. Our results indicate that ascending visceral afferents, VPLpc, VPMpc, and parabrachial nuclei, are topographically organized in the granular and dysgranular fields of the insular cortex, whereas the agranular cortex appears to receive highly integrated limbic afferents from the infralimbic cortex and the mediodorsal nucleus of the thalamus. Although these visceral and limbic inputs to the insular cortex are segregated for the most part into different longitudinally oriented strips of cortex, limbic input from the lateral hypothalamic area and the amygdala, which have extensive autonomic as well as limbic connections, are more diffusely distributed over the different regions of the insular cortex. This organization may subserve a role for the insular cortex in integration of autonomic response with ongoing behaviour and emotion.

Afferent Pathways↗

Origin of porcine brain natriuretic peptide-like immunoreactive innervation of the middle cerebral artery in the rat.

We recently demonstrated that porcine brain natriuretic peptide-like immunoreactive (pBNPir) fibers innervate parts of the cardiovascular system, including the arteries comprising the circle of Willis. To determine the origin of this innervation, we used the retrograde fluorescent tracer Fast Blue dye combined with pBNP immunocytochemistry. Cells which project to the middle cerebral artery and were also pBNPir were found in the trigeminal, pterygopalatine and superior cervical ganglia bilaterally but not in the geniculate or otic ganglia. The majority of these double-labelled cells were found in the ipsilateral trigeminal (46%) and superior cervical ganglia (34%). A pBNP-like substance may be a natural vasodilator in sympathetic, sensory and to a lesser extent parasympathetic neurons innervating the cerebrovascular system.

Amidines↗

Efferent projections of the infralimbic cortex of the rat.

On the basis of stimulation studies, it has been proposed that the infralimbic cortex (ILC), Brodmann area 25, may serve as an autonomic motor cortex. To explore this hypothesis, we have combined anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) and retrograde tracing with wheat germ aggutinin conjugated to horseradish peroxidase (WGA-HRP) to determine the efferent projections from the ILC. Axons exit the ILC in one of three efferent pathways. The dorsal pathway ascends through layers III and V to innervate the prelimbic and anterior cingulate cortices. The lateral pathway courses through the nucleus accumbens to innervate the insular cortex, the perirhinal cortex, and parts of the piriform cortex. In addition, some fibers from the lateral pathway enter the corticospinal tract. The ventral pathway is by far the largest and innervates the thalamus (including the paraventricular nucleus of the thalamus, the border zone between the paraventricular and medial dorsal nuclei, and the paratenial, reuniens, ventromedial, parafasicular, and subparafasicular nuclei), the hypothalamus (including the lateral hypothalamic and medial preoptic areas, and the suprachiasmatic, dorsomedial, and supramammillary nuclei), the amygdala (including the central, medial, and basomedial nuclei, and the periamygdaloid cortex) and the bed nucleus of the stria terminalis. The ventral efferent pathway also provides descending projections to autonomic cell groups of the brainstem and spinal cord including the periaqueductal gray matter, the parabrachial nucleus, the nucleus of the solitary tract, the dorsal motor vagal nucleus, the nucleus ambiguus, and the ventrolateral medulla, as well as lamina I and the intermediolateral column of the spinal cord. The ILC has extensive projections to central autonomic nuclei that may subserve a role in modulating visceral responses to emotional stimuli, such as stress.

Animals↗

Calcitonin gene-related peptide (CGRP) immunoreactive projections from the thalamus to the striatum and amygdala in the rat.

The organization of calcitonin gene-related peptide-like immunoreactive (CGRPir) innervation of the amygdala and caudate-putamen in the rat was examined by using immunohistochemistry for CGRP combined with retrograde transport of the fluorescent dye fluoro-gold, as well as anterograde transport of Phaseoleus vulgaris leucoagglutinin (PHA-L). The lateral part of the central nucleus of the amygdala and the amygdalostriatal transition zone was densely innervated by CGRPir terminals at all anterior-posterior levels. More caudally, the lateral part of the caudate-putamen also had large numbers of CGRPir terminals. Injections of fluoro-gold into the amygdala and amygdalostriatal transition area followed by immunohistochemistry for CGRP revealed double-labeled neurons in the subparafascicular, lateral subparafascicular, and posterior intralaminar nuclei of the thalamus and peripeduncular nucleus. Injections into the caudate-putamen demonstrated double-labeled neurons in the more lateral parts of this same nuclear complex. PHA-L injections into the posterior thalamic nuclei from which the CGRPir projections arise confirmed the medial-to-lateral organization of the projections to the amygdala and striatum. The subparafascicular nucleus and the rostral portion of the lateral subparafascicular nucleus primarily projected to the medial amygdala and the amygdalostriatal transition area, while the more lateral cell groups, including the caudal part of the lateral parafascicular, posterior intralaminar, and peripeduncular nuclei projected to the lateral amygdala and the caudate-putamen. These CGRPir projections may be involved in mediating conditioned autonomic and behavioral responses to acoustic stimuli or somatosensory stimuli.

Amygdala↗

Autonomic responses and efferent pathways from the insular cortex in the rat.

The anatomical distribution of autonomic, particularly cardiovascular, responses originating in the insular cortex was examined by using systematic electrical microstimulation. The localization of these responses to cell bodies in the insular cortex was demonstrated by using microinjection of the excitatory amino acid, D,L-homocysteic acid. The efferents from the cardiovascular responsive sites were traced by iontophoretic injection of the anterograde axonal tracer Phaseoleus vulgaris leucoagglutinin (PHA-L). Two distinct patterns of cardiovascular response were elicited from the insular cortex: an increase in arterial pressure accompanied by tachycardia or a decrease in arterial pressure with bradycardia. The pressor responses were obtained by stimulation of the rostral half of the posterior insular cortex while depressor sites were located in the caudal part of the posterior insular area. Both types of site were primarily located in the dysgranular and agranular insular cortex. Gastric motility changes originated from a separate but adjacent region immediately rostral to the cardiovascular responsive sites in the anterior insular cortex. Tracing of efferents with PHA-L indicated a number of differences in connectivity between the pressor and depressor sites. Pressor sites had substantially more intense connections with other limbic regions including the infralimbic cortex, the amygdala, the bed nucleus of the stria terminalis and the medial dorsal and intralaminar nuclei of the thalamus. Alternatively, the depressor region of the insular cortex more heavily innervated sensory areas of the brain including layer I of the primary somatosensory cortex, a peripheral region of the sensory relay nuclei of the thalamus and the caudal spinal trigeminal nucleus. In addition, there were topographical differences in the projection to the lateral hypothalamic area, the primary site of autonomic outflow for these responses from the insular cortex. These differences in connectivity may provide the anatomic substrate for the specific cardiovascular responses and behaviors integrated in the insular cortex.

Animals↗

Medullary catecholaminergic neurons in the normal human brain and in Parkinson's disease.

Parkinson's disease is thought to cause degeneration of melanin-pigmented catecholaminergic neurons throughout the brainstem, but little quantitative information is available on the fate of catecholaminergic neurons associated with the dorsal vagal complex or medullary reticular formation. We therefore examined these neurons in the normal human medulla and in the brains of patients with Parkinson's disease, using both a melanin stain and immunohistochemical methods with an antiserum against tyrosine hydroxylase. The greatest numbers of catecholaminergic neurons in the ventrolateral reticular formation (A1/C1 group) were located in the far rostral medulla, whereas the largest populations of catecholaminergic cells in the dorsal vagal complex (A2/C2 group) were found at the level of the area postrema. No loss of cells was observed in the A1/C1 group in the parkinsonian brains. In contrast, the A2/C2 group showed moderate loss of neurons, most marked at the level of the area postrema. This difference was entirely due to the loss of neurons in the medial component of the A2 group, a population that normally is only lightly pigmented, while the heavily pigmented neurons in the ventral and intermediate components of the A2 complex were unaffected. Parkinson's disease causes degeneration only of selected populations of medullary catecholaminergic neurons, without apparent relationship to the extent of melanin pigmentation.

Catecholamines↗

Evidence for a cholinergic projection from the pedunculopontine tegmental nucleus to the rostral ventrolateral medulla in the rat.

Recent studies indicate that cholinergic innervation of the rostral ventrolateral medulla (RVL) may play an important role in regulation of blood pressure, but the origin of this input is not known. Using retrograde fluorescent tracing combined with immunohistochemistry for choline acetyltransferase, we found that as many as 10% of the cholinergic neurons in the pedunculopontine tegmental nucleus (PPT) can be retrogradely labeled from the RVL. Anterograde tracing of this pathway with PHA-L demonstrated that descending fibers from the region of the PPT ramify and give off terminal boutons in the RVL. These studies indicate that PPT may be a major source of cholinergic afferents to the RVL.

Animals↗

Organization of cortical, basal forebrain, and hypothalamic afferents to the parabrachial nucleus in the rat.

In a previous study (Herbert et al., J. Comp. Neurol. [1990];293:540-580), we demonstrated that the ascending afferent projections from the medulla to the parabrachial nucleus (PB) mark out functionally specific terminal domains within the PB. In this study, we examine the organization of the forebrain afferents to the PB. The PB was found to receive afferents from the infralimbic, the lateral prefrontal, and the insular cortical areas; the dorsomedial, the ventromedial, the median preoptic, and the paraventricular hypothalamic nuclei; the dorsal, the retrochiasmatic, and the lateral hypothalamic areas; the central nucleus of the amygdala; the substantia innominata; and the bed nucleus of the stria terminalis. In general, forebrain areas tend to innervate the same PB subnuclei from which they receive their input. Three major patterns of afferent termination were noted in the PB; these corresponded to the three primary sources of forebrain input to the PB: the cerebral cortex, the hypothalamus, and the basal forebrain. Hypothalamic afferents innervate predominantly rostral portions of the PB, particularly the central lateral and dorsal lateral subnuclei. The basal forebrain projection to the PB ends densely in the external lateral and waist subnuclei. Cortical afferents terminate most heavily in the caudal half of the PB, particularly in the ventral lateral and medial subnuclei. In addition, considerable topography organization was found within the individual projections. For example, tuberal lateral hypothalamic neurons project heavily to the central lateral subnucleus and lightly to the waist area; in contrast, caudal lateral hypothalamic neurons send a moderately heavy projection to both the central lateral and waist subnuclei. Our results show that the forebrain afferents of the PB are topographically organized. These topographical differences may provide a substrate for the diversity of visceral functions associated with the PB.

Animals↗

Neuropeptide organization of the hypothalamic projection to the parabrachial nucleus in the rat.

The hypothalamus is a major source of afferents to the parabrachial nucleus (PB), but the neurotransmitters in this pathway are largely unknown. In this study, we examine the neuropeptide immunoreactivities of neurons in the hypothalamus that project to the PB by using the combined retrograde fluorescence-immunofluorescence method. After injections of the fluorescent tracer fast blue into the PB, retrogradely labeled neurons were observed in the paraventricular, dorsomedial, ventromedial, median preoptic, and anteroventral periventricular hypothalamic nuclei; in the dorsal, retrochiasmatic, and lateral hypothalamic areas; and in the medial and lateral preoptic areas. Our results show that at least five distinct neuropeptide-immunoreactive cell populations in the hypothalamus project to the PB. In the perifornical lateral hypothalamus, many neurotensin (NT)-, corticotropin-releasing factor-, dynorphin (DYN)-, angiotensin II (AII)-, and galanin-like immunoreactive (-ir) neurons were retrogradely labeled. A cluster of retrogradely labeled neurons in the juxtacapsular lateral hypothalamus stained with an antiserum against alpha-melanocyte stimulating hormone (alpha MSH). Over 50% of the retrogradely labeled cells in the arcuate nucleus were adrenocorticotropin (ACTH)-or alpha MSH-ir. Many alpha MSH- and ACTH-ir, and a few DYN-, NT- and AII-ir neurons in the retrochiasmatic area were retrogradely labeled. Only small numbers of double-labeled neurons were found in the paraventricular nucleus, and, of these, enkephalin-ir and dynorphin-ir neurons were the most common. Somatostatin-ir cells in the hypothalamus were rarely double-labeled. The chemical coding of these hypothalamic projections to the PB may provide important clues to the functional organization of these descending pathways.

Animals↗

Connections of the parabrachial nucleus with the nucleus of the solitary tract and the medullary reticular formation in the rat.

We examined the subnuclear organization of projections to the parabrachial nucleus (PB) from the nucleus of the solitary tract (NTS), area postrema, and medullary reticular formation in the rat by using the anterograde and retrograde transport of wheat germ agglutinin-horseradish peroxidase conjugate and anterograde tracing with Phaseolus vulgaris-leucoagglutinin. Different functional regions of the NTS/area postrema complex and medullary reticular formation were found to innervate largely nonoverlapping zones in the PB. The general visceral part of the NTS, including the medial, parvicellular, intermediate, and commissural NTS subnuclei and the core of the area postrema, projects to restricted terminal zones in the inner portion of the external lateral PB, the central and dorsal lateral PB subnuclei, and the "waist" area. The dorsomedial NTS subnucleus and the rim of the area postrema specifically innervate the outer portion of the external lateral PB subnucleus. In addition, the medial NTS innervates the caudal lateral part of the external medial PB subnucleus. The respiratory part of the NTS, comprising the ventrolateral, intermediate, and caudal commissural subnuclei, is reciprocally connected with the Kölliker-Fuse nucleus, and with the far lateral parts of the dorsal and central lateral PB subnuclei. There is also a patchy projection to the caudal lateral part of the external medial PB subnucleus from the ventrolateral NTS. The rostral, gustatory part of the NTS projects mainly to the caudal medial parts of the PB complex, including the "waist" area, as well as more rostrally to parts of the medial, external medial, ventral, and central lateral PB subnuclei. The connections of different portions of the medullary reticular formation with the PB complex reflect the same patterns of organization, but are reciprocal. The periambiguus region is reciprocally connected with the same PB subnuclei as the ventrolateral NTS; the rostral ventrolateral reticular nucleus with the same PB subnuclei as both the ventrolateral (respiratory) and medial (general visceral) NTS; and the parvicellular reticular area, adjacent to the rostral NTS, with parts of the central and ventral lateral and the medial PB subnuclei that also receive rostral (gustatory) NTS input. In addition, the rostral ventrolateral reticular nucleus and the parvicellular reticular formation have more extensive connections with parts of the rostral PB and the subjacent reticular formation that receive little if any NTS input. The PB contains a series of topographically complex terminal domains reflecting the functional organization of its afferent sources in the NTS and medullary reticular formation.

Animals↗