Parabrachial Subnucleus Research Articles

Naloxone blocks the aversive effects of electrical stimulation of the parabrachial complex in a place discrimination task

The parabrachial complex is known to participate in various rewarding and aversive processes, including those related to the learning of taste or place discrimination and the motivational effects of drugs of abuse, such as morphine. This study shows that electrical stimulation of the external lateral parabrachial (LPBe) subnucleus induces consistent place avoidance or place preference in three-compartment rectangular mazes. Administration of naloxone, an opiate antagonist, blocks both motivational effects induced by the intracranial electrical stimulation. Subsequent re-administration of the electrical stimulation was found to recover its aversive but not its rewarding effects after vehicle administration. These results are discussed in relation to different natural and artificial agents involved in the induction of avoidance and preference motivational processes, especially with regard to the opioid system.

Characterization of Parabrachial Subnuclei in Mice with Regard to Salt Tastants: Possible Independence of Taste Relay from Visceral Processing

We examined whether salt taste and/or abdominal illness were dealt within different subnuclei in the parabrachial nucleus (PBN) in mice, using retrograde tracing methods and c-Fos-like immunoreactivity (FLI) detection procedures. Some PBN subnuclei have distinct functions and receive various sensory inputs from the nucleus of the solitary tract (NTS) and other areas and relay them to the higher order nuclei such as the thalamus. The afferent-dependent pattern of FLI has been investigated in the PBN. However, it is unclear in which PBN subnuclei the tastants induce c-Fos, or whether PBN subnuclei process taste inputs separately from other inputs, or integrate them. After the tracer injections into the thalamic taste relay, the retrograde labeled cells revealed the taste relay cells in the PBN at the boundary with the superior cerebellar peduncle of both the inner part of the external lateral subnucleus and the medial subnucleus and in the waist area. On the other hand, NaCl intake induced intense FLI in the dorsal lateral subnucleus, whereas LiCl intake yielded intense FLI in both the dorsal lateral subnucleus and the outer part of the external lateral subnucleus. Thus, the present findings that subnuclei relaying taste information to the thalamus do not yield FLI in response to salt taste and abdominal illness indicate that they lack FLI yielding pathways or that they are independent from the subnuclei processing salt taste and visceral information via c-Fos in mice.

Expression of c-Fos in the parabrachial nucleus following peripheral nerve injury in rats

Chronic constriction injury (CCI) of the sciatic nerve in rats evokes c-Fos expression at spinal cord level. Using immunohistochemical methods we studied changes in c-Fos expression in the brain stem area, which is suggested as one of the major targets of projection neurons in the superficial dorsal horn laminae, i.e., the parabrachial area. During the first week following injury, the animals developed tactile allodynia. At this time we found an increase of c-Fos positive neurons in the parabrachial area, mainly in the pontine part where the group of c-Fos immunoreactive neurons was present in the dorsal part of lateral parabrachial subnuclei. The number of c-Fos positive neurons gradually decreased up to 14 days following CCI. The specific activation of brain stem neurons during onset of mechanical allodynia could underlie the changes in central nociceptive processing following peripheral nerve injury.

Lateral parabrachial lesions impair lithium chloride-induced aversive responses but not saccharin-induced flavor preference

Behavioral taste-guided experiments, as well as molecular studies employing c-FLI expression in response to aversive/appetitive unconditioned stimulus, have strongly suggested a visceral role for the lateral parabrachial subnuclei (lPB). The main objective in the present study was to further evaluate the functional role of the lPB in lithium chloride-induced behavioral/physiological responses. We employed a lesion/behavioral experimental strategy combining a lithium chloride-induced place aversion procedure together with the simultaneous evaluation of behavioral (“Lying on Belly”, “LOB”) and physiological (body temperature) responses elicited by the toxin. Data showed that lPB-lesioned animals failed to avoid the chamber previously paired with lithium chloride. Moreover, “LOB”, and not hypothermia, in response to lithium chloride was impaired in parabrachial lesioned animals. Finally, all the animals were tested in a free discriminative flavor-preference task induced by saccharin, a non-caloric reinforcer, which precludes visceral feedback as essential in acquiring the learned response. As expected, both control and lesioned animals developed a clear flavor-preference to the flavor previously paired with saccharin, which shows normal gustatory and associative processing in lPB-lesioned animals. This study extends previous results on the functional visceral role of lPB subnuclei by providing alternative behavioral evidence other than taste-guided behavior, that the lPB is pivotal in visceral processing. Present data are discussed in the context of the visceral hypothesis that holds that the lPB is critically involved in processing post-oral visceral feedback.

Increased c-Fos expression in select lateral parabrachial subnuclei following chemical versus electrical stimulation of the dorsal periaqueductal gray in rats

The parabrachial nucleus (PBN) is located in the rostral dorsolateral pons and has been identified as a critical relay for cardiovascular responses (sympathoexcitation and baroreflex attenuation) evoked by the dorsal periaqueductal gray (PAG). We examined the pattern of c-Fos protein immunoreactivity throughout the rostral-caudal extent of the PBN in four groups of anesthetized male Sprague–Dawley rats to identify the specific PBN regions activated by dorsal PAG stimulation. Both electrical stimulation and chemical (0.3 mM bicuculline methobromide) activation of the dorsal PAG elicited a selective increase in Fos-like immunoreactivity (FLI) in the superior lateral and central lateral subnuclei of the rostral lateral PBN (LPBN) relative to surgery and blood pressure control groups. In the middle LPBN chemical stimulation of the dorsal PAG selectively increased FLI in the central lateral subnucleus while electrical stimulation increased FLI in the Kolliker-Fuse area only. Finally, in the caudal LPBN only electrical stimulation of the dorsal PAG induced significant changes in FLI above control. Significant changes in FLI in the medial PBN were not observed under any experimental conditions. These results confirm neuroanatomical data demonstrating that neurons in superior lateral and central lateral subnuclei of the rostral and middle LPBN are the primary targets of the dorsal PAG. Our results also demonstrate that this descending projection to the central lateral and superior lateral subnuclei of the LPBN is in part excitatory. Finally, our results raise the possibility that neurons in the central lateral subnucleus of the middle and rostral LPBN are integrally involved in descending modulation of sympathetic drive associated with dorsal PAG activation.

The role of the external lateral parabrachial subnucleus in flavor preferences induced by predigested food administered intragastrically

A study was undertaken of the role of the external lateral parabrachial subnucleus (PBNLe) in flavor preferences induced by the intragastric administration of predigested/cephalic food. These preferences were developed using two different learning procedures, concurrent and sequential. In the concurrent procedure, two different-flavored stimuli were presented at the same time: one stimulus was paired with the simultaneous intragastric administration of partially digested food and the other with physiological saline. In the sequential learning procedure, the two stimuli were presented at alternate sessions. The results showed that PBNLe lesions blocked acquisition of concurrent learning but had no effect on the sequential procedure. In the latter case, both lesioned and control animals showed a strong preference for the gustatory stimulus paired with partially digested food. These results are interpreted in terms of a dual neurobiological system involved in the rewarding effects of visceral signals.

The role of the lateral parabrachial nuclei in concurrent and sequential taste aversion learning in rats

The purpose of this study was to examine the role of the external lateral parabrachial subnucleus (PBNLe) in two different taste aversion learning (TAL) procedures. For the first, short-term (concurrent) TAL, two different-flavored stimuli were presented at the same time, one associated with simultaneous intragastric administration of an aversive product, hypertonic NaCl, and the other with saline. In the second, long-term (sequential/delayed) TAL, each gustatory stimulus was presented every other day and the intragastric products LiCl and saline were administered after a 15-min delay. Electrolytic lesions in the PBNLe blocked acquisition of concurrent TAL, in which the vagal visceral information is critical. But the same lesions failed to interrupt sequential TAL. This result was independent of the order in which the two tasks (concurrent and sequential) were presented. However, as found by other authors, the latter type of learning was impaired in the presence of larger lesions in this same area. This supports the existence of sensory information needed to establish sequential TAL in other subnuclei of the parabrachial complex. The results of these experiments suggest that the different modalities of TAL are anatomically specific.

Calcitonin gene-related peptide-like immunoreactivity marks putative visceral sensory pathways in human brain

Calcitonin gene-related peptide serves as a neuromodulator in several ascending visceral sensory pathways from the parabrachial nucleus to the thalamus, amygdala and the visceral sensory cortex in rats, but these pathways have not been studied in primates. We have examined the distribution of calcitonin gene-related peptide-like immunoreactive innervation of the corresponding areas of the human brain, including the cortex, diencephalon and brainstem. We report the finding of three populations of calcitonin gene-related peptide-like immunoreactive cells that are homologous to those that have been characterized in the rat: the external lateral and external medial parabrachial subnuclei and the posterior intralaminar thalamic complex, including the subparafascicular, lateral subparafascicular and peripeduncular nuclei. In addition, scattered calcitonin gene-related peptide-like immunoreactive cells were found in the periventricular hypothalamus. Calcitonin gene-related peptide-like immunoreactive terminals were found in regions homologous to the projection areas of the external medial and external lateral parabrachial subnuclei in the rat, including the ventroposterior parvicellular nucleus of the thalamus, the central nucleus of the amygdala, the bed nucleus of the stria terminalis and the insular cortex; and in the terminal field of the posterior intralaminar thalamic complex, including the amygdalo-striatal transition region and the insular cortex. These results suggest that, similarly to other species, calcitonin gene-related peptide may also serve as a marker for ascending visceral sensory pathways in the human brain.

Parabrachial nucleus projections to midline and intralaminar thalamic nuclei of the rat.

The projections from the parabrachial nucleus to the midline and intralaminar thalamic nuclei were examined in the rat. Stereotaxic injections of the retrograde tracer cholera toxin-beta (CTb) were made in each of the intralaminar nuclei of the dorsal thalamus (the lateral parafascicular, medial parafascicular, oval paracentral, central lateral, paracentral, and central medial nuclei), as well as the midline thalamic nuclei (the paraventricular, intermediodorsal, mediodorsal, paratenial, rhomboid, reuniens, parvicellular part of the ventral posterior, and caudal ventral medial nuclei). The retrograde cell body labeling pattern within the parabrachial subnuclei was then analyzed. The paracentral thalamic nucleus received an input only from the internal lateral parabrachial subnucleus. However, this subnucleus also projected to all the other intralaminar thalamic nuclei, except for the central lateral thalamic nucleus, which received no parabrachial afferent inputs. The external lateral parabrachial subnucleus projected to the lateral parafascicular, reuniens, central medial, parvicellular part of the ventral posterior, and caudal ventromedial thalamic nuclei. Following CTb injections in the paraventricular thalamic nucleus, retrogradely labeled cells were found in the central lateral, dorsal lateral, and external lateral parabrachial subnuclei. The medial and ventral lateral parabrachial subnuclei projected to the oval paracentral, parafascicular, and rhomboid thalamic nuclei. Finally, the waist area of the parabrachial nucleus was densely labeled after CTb injections in the parvicellular part of the ventral posterior thalamic nucleus. Nociceptive, visceral, and gustatory signals may reach specific cortical and other forebrain sites via this parabrachial-thalamic pathway.

Differential projections to the intralaminar and gustatory thalamus from the parabrachial area: A PHA-L study in the rat

The organization of projections from the parabrachial (PB) area to the ventral posterior parvicellular (VPpc) "gustatory" and intralaminar nuclei of the thalamus was studied in the rat by using microinjections of Phaseolus vulgaris leucoagglutinin (PHA-L), into subregions of the PB area. The present study is a follow-up of three former studies (Bernard et al. [1993] J. Comp. Neurol. 329:201-229; Aldén et al. [1994] J. Comp. Neurol. 341:289-314; Bester et al. [1997a] J. Comp. Neurol. 383:245-281) that examined PB projections onto the amygdala, the bed nucleus of the stria terminalis, and the hypothalamus. Our data showed that (1) the region centered in the internal lateral PB subnucleus projects densely with a bilateral and symmetric pattern to the caudal portion of the paracentral and, to a lesser extent, to the adjacent portion of the central and parafascicular medial thalamic nuclei; (2) the mesencephalic PB region centered in the ventral lateral subnucleus and scattered neurons in the subjacent brachium conjunctivum project primarily, although diffusely, to the central medial thalamic nucleus. The third region includes two subgroups: (3a) the medial subgroup, including the medial, the waist area, and the ventral lateral subnuclei of the pontine PB area, projects bilaterally but with a weak ipsilateral predominance to the VPpc, terminals bearing large varicosities. Additionally, a diffuse projection with small varicosities spreads in the area between the two VPpc nuclei and the central medial nucleus. (3b) The lateral subgroup, centered in the external medial subnucleus, projects with a contralateral predominance in the periphery of the VPpc nuclei, most terminals being located around the dorsomedial tip. It is suggested that the PB projections to the intralaminar nucleus could be involved in cortical limbic arousal processing in relation with nociceptive, (somatic, visceral, and intraoral) and gustatory aversive stimuli. The projection with large varicosities inside the VPpc could process gustatory discrimination.

Differential projections to the intralaminar and gustatory thalamus from the parabrachial area: A PHA‐L study in the rat

The organization of projections from the parabrachial (PB) area to the ventral posterior parvicellular (VPpc) “gustatory” and intralaminar nuclei of the thalamus was studied in the rat by using microinjections of Phaseolus vulgaris leucoagglutinin (PHA-L), into subregions of the PB area. The present study is a follow-up of three former studies (Bernard et al. [1993] J. Comp. Neurol. 329:201–229; Aldén et al. [1994] J. Comp. Neurol. 341:289–314; Bester et al. [1997a] J. Comp. Neurol. 383:245–281) that examined PB projections onto the amygdala, the bed nucleus of the stria terminalis, and the hypothalamus. Our data showed that (1) the region centered in the internal lateral PB subnucleus projects densely with a bilateral and symmetric pattern to the caudal portion of the paracentral and, to a lesser extent, to the adjacent portion of the central and parafascicular medial thalamic nuclei; (2) the mesencephalic PB region centered in the ventral lateral subnucleus and scattered neurons in the subjacent brachium conjunctivum project primarily, although diffusely, to the central medial thalamic nucleus. The third region includes two subgroups: (3a) the medial subgroup, including the medial, the waist area, and the ventral lateral subnuclei of the pontine PB area, projects bilaterally but with a weak ipsilateral predominance to the VPpc, terminals bearing large varicosities. Additionally, a diffuse projection with small varicosities spreads in the area between the two VPpc nuclei and the central medial nucleus. (3b) The lateral subgroup, centered in the external medial subnucleus, projects with a contralateral predominance in the periphery of the VPpc nuclei, most terminals being located around the dorsomedial tip. It is suggested that the PB projections to the intralaminar nucleus could be involved in cortical limbic arousal processing in relation with nociceptive, (somatic, visceral, and intraoral) and gustatory aversive stimuli. The projection with large varicosities inside the VPpc could process gustatory discrimination. J. Comp. Neurol. 405:421–449, 1999. © 1999 Wiley-Liss, Inc.

Subnuclear localization of FOS-like immunoreactivity in the parabrachial nucleus after orofacial nociceptive stimulation of the awake rat

We used FOS-like immunohistochemistry to detect neuronal activity in the pontine parabrachial nucleus after injection of formalin into the lower lip of the awake rat and compared the labeling pattern with that seen after formalin injection into the hindpaw. One hour after a formalin injection into the lip, many FOS-immunoreactive cells were seen in the parabrachial nucleus, preferentially on the side ipsilateral to the injection site. Detailed anatomical analysis revealed that FOS-immunoreactive neurons were localized predominantly to three regions of the parabrachial nucleus: the external lateral, the external medial, and the Kölliker-Fuse subnuclei, with sparser labeling present in the dorsal and superior lateral subnuclei and in the medial parabrachial nucleus. In contrast, a formalin injection into the hindpaw resulted in dense FOS-labeling in the superior, dorsal, and central lateral subnuclei, with sparse to moderate labeling in the Kölliker-Fuse nucleus, and sparse labeling in the external lateral and external medial subnuclei, as described previously (Hermanson and Blomqvist, J. Comp. Neurol., [1996] 368:45-56). The distribution of FOS-labeled neurons after noxious orofacial stimulation corresponds to the termination pattern in the parabrachial nucleus of fibers that originate from neurons in the marginal zone of the trigeminal dorsal horn and is different from that seen after nociceptive stimulation of other body parts. Considering the differences in efferent connections of parabrachial subnuclei, the present findings imply that noxious information from the orofacial region to the parabrachial nucleus has other functional roles than noxious information from the trunk and limbs. Such roles may include the integration of somatosensory and gustatory information, which has been suggested to be of importance for feeding behavior.

Subnuclear localization of FOS‐like immunoreactivity in the parabrachial nucleus after orofacial nociceptive stimulation of the awake rat

We used FOS-like immunohistochemistry to detect neuronal activity in the pontine parabrachial nucleus after injection of formalin into the lower lip of the awake rat and compared the labeling pattern with that seen after formalin injection into the hindpaw. One hour after a formalin injection into the lip, many FOS-immunoreactive cells were seen in the parabrachial nucleus, preferentially on the side ipsilateral to the injection site. Detailed anatomical analysis revealed that FOS-immunoreactive neurons were localized predominantly to three regions of the parabrachial nucleus: the external lateral, the external medial, and the Kölliker-Fuse subnuclei, with sparser labeling present in the dorsal and superior lateral subnuclei and in the medial parabrachial nucleus. In contrast, a formalin injection into the hindpaw resulted in dense FOS-labeling in the superior, dorsal, and central lateral subnuclei, with sparse to moderate labeling in the Kölliker-Fuse nucleus, and sparse labeling in the external lateral and external medial subnuclei, as described previously (Hermanson and Blomqvist, J. Comp. Neurol., [1996] 368:45–56). The distribution of FOS-labeled neurons after noxious orofacial stimulation corresponds to the termination pattern in the parabrachial nucleus of fibers that originate from neurons in the marginal zone of the trigeminal dorsal horn and is different from that seen after nociceptive stimulation of other body parts. Considering the differences in efferent connections of parabrachial subnuclei, the present findings imply that noxious information from the orofacial region to the parabrachial nucleus has other functional roles than noxious information from the trunk and limbs. Such roles may include the integration of somatosensory and gustatory information, which has been suggested to be of importance for feeding behavior. J. Comp. Neurol. 387:114–123, 1997. © 1997 Wiley-Liss, Inc.

Differential distribution of AMPA-selective glutamate receptor subunits in the parabrachial nucleus of the rat

The parabrachial complex is made up of at least 11 cytoarchitectonically distinct subnuclei which differ in their anatomical connections and neurotransmitter content, as well as the functions they subserve. To determine whether parabrachial subnuclei also express different types of glutamate receptors, we undertook a light microscopic examination of the regional distribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor subunits within the parabrachial complex using antibodies directed against synthetic peptides corresponding to the C-terminal parts of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor subunits. Antibodies that recognize GluR1 subunits stained cells mainly in the central lateral parabrachial subnucleus, whereas GluR4 antibodies selectively stained cells in the internal lateral subnucleus. In contrast, antibodies directed against the GLuR2/3 subunits stained neurons in every parabrachial subnucleus, although the most dense labelling was seen in the external lateral cell group. These differences in expression of alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionate receptor subtypes may eventually allow selective activation or inhibition of specific subsets of neurons in the parabrachial complex.

Organization of the efferent projections from the spinal cervical enlargement to the parabrachial area and periaqueductal gray: a PHA-L study in the rat.

The organization of efferent projections from the spinal cervical enlargement to the parabrachial (PB) area and the periaqueductal gray (PAG) was studied in the rat by using microinjections of Phaseolus vulgaris-leucoagglutinin (PHA-L) into different laminae around the C7 level. The results demonstrated two areas of cervical enlargement which project in different ways to the PB area and PAG. First, the superficial laminae (I, II) showed a very dense projection, with a clear contralateral dominance at the coronal level where the inferior colliculus merges with the pons, to a restricted "superficial" portion of the PB area, namely the lateral crescent area, the dorsal lateral, the superior lateral (PBsl), and the outer portion of the external lateral PB subnuclei. Less dense projections were observed in the Kölliker-Fuse nucleus (KF) and in the ventrolateral/lateral quadrant of the caudal and mid PAG. By contrast, the labeling was weak or absent in the other PB subnuclei and the outer adjacent regions; in particular, no, or very little, labeling was found in the cuneiform nucleus. The PB area appeared to be the supraspinal target that received the densest projection from laminae I and II. Projections were less dense in the PAG and the thalamus and markedly less in other sites such as the ventrolateral medulla, the subnucleus reticularis dorsalis, and the nucleus of the solitary tract. Second, the reticular portion of lamina V, the medial portion of laminae IV-VI up to X and lamina VIII, showed bilateral projections with a weak ipsilateral dominance and a high to medium density on a very restricted portion of the PB area, namely the internal lateral PB subnucleus. A lesser projection was also observed in the adjacent portion of the PBsl, the KF, and the lateral quadrant of the PAG. These results suggest that signals carried by neurons from lamina I-II converge on a restricted superficial portion of the PB area and the ventral part of the lateral quadrant of the PAG. These results are discussed in the context of the role of the spino-PB and spino-PAG pathways in nociception.

Lateral parabrachial subnucleus lesions abolish feeding induced by mercaptoacetate but not by 2-deoxy-D-glucose

Lesions of the area postrema/nucleus of the solitary tract (AP/NTS) region abolish feeding induced by mercaptoacetate (MA) and 2-deoxy-D-glucose (2DG), metabolic inhibitors that selectively impair fatty acid and glucose utilization, respectively. Because the AP/NTS region is important for both MA- and 2DG-induced feeding, the present experiment investigated the involvement of the lateral parabrachial nucleus (1PBN), which is innervated by AP/NTS neurons, in these feeding responses. Electrolytic and ibotenic acid lesions were directed at the entire parabrachial nucleus or at specific lateral parabrachial subnuclei. Rats with electrolytic lesions were tested for feeding in response to 0.9% NaCl (subcutaneous or intraperitoneal), MA (400, 600, and 800 mumol/kg ip), and 2DG (100 and 200 mg/kg sc). Ibotenate-lesioned rats were tested with NaCl and MA only. Lesions were verified either by cresyl violet staining or by glial fibrillary acidic protein immunohistochemistry. Bilateral destruction of the 1PBN severely impaired or abolished MA-induced feeding. Cell bodies important for MA-induced feeding appear to be localized in the dorsal-central 1PBN subnuclear area, because both electrolytic and cytotoxin microlesions centered in this area abolished feeding in response to MA. Fibers of passage important for MA-induced feeding appear to pass through the external and superior 1PBN because electrolytic but not cytotoxin lesions of these subnuclei disrupted the feeding response. In contrast, 2DG-induced feeding did not differ significantly from sham-lesioned controls in any of the 1PBN lesion groups. These results indicate that 2DG and MA stimulate feeding by activating separate central neural pathways and, perhaps, distinct metabolic controls of food intake.

Projections of the parabrachial nucleus in the pigeon (Columba livia)

The ascending and descending projections of the parabrachial nuclear complex in the pigeon have been charted with autoradiographic and histochemical (WGA-HRP) techniques. The ascending projections originate from a group of subnuclei surrounding various components of the brachium conjunctivum, namely, the superficial lateral, dorsolateral, dorsomedial, and ventromedial subnuclei. The projections are predominantly ipsilateral and travel in the quintofrontal tract. They are primarily to the medial and lateral hypothalamus (including the periventricular nucleus and the strata cellulare internum and externum), certain dorsal thalamic nuclei, the nucleus of the pallial commissure, the bed nucleus of the stria terminalis, the ventral paleostriatum, the olfactory tubercle, the nucleus accumbens, and a dorsolateral nucleus of the posterior archistriatum. There are weaker or more diffuse projections to the rostral locus coeruleus (cell group A8), the compact portion of the pedunculopontine tegmental nucleus, the central grey and intercollicular region, the ventral area of Tsai, the medial spiriform nucleus, the nucleus subrotundus, the anterior preoptic area, and the diagonal band of Broca. The parabrachial subnuclei have partially differential projections to these targets, some of which also receive projections from the nucleus of the solitary tract (Arends, Wild, and Zeigler: J. Comp. Neurol. 278:405-429, '88). Most of the targets, particularly those in the basal forebrain (viz., the periventricular nucleus and the strata cellulare internum and externum of the hypothalamus, the bed nucleus of the stria terminalis, and its lateral extension into the ventral paleostriatum, which may be comparable with the substantia innominata), have reciprocal connections with the parabrachial and solitary tract subnuclei and therefore may be said to compose parts of a "visceral forebrain system" analogous to that described in the rat (Van der Kooy et al: J. Comp. Neurol. 224:1-24, '84). The descending projections to the lower brainstem arise in large part from a ventrolateral subnucleus that may be comparable with the Kölliker-Fuse nucleus of mammals. They are mainly to the ventrolateral medulla, nucleus ambiguus, and massively to the hypoglossal nucleus, particularly its tracheosyringeal portion. These projections are therefore likely to be importantly involved in the control of vocalization and respiration (Wild and Arends: Brain Res. 407:191-194, '87). Some of these results have been presented in abstract form (Wild, Arends, and Zeigler: Soc. Neurosci. Abst. 13:308, '87).

Calcitonin gene-related peptide immunoreactivity in the visceral sensory cortex, thalamus, and related pathways in the rat.

It has been proposed that calcitonin gene-related peptide (CGRP) may serve as a major neuromodulator in visceral sensory pathways, but its exact role in the visceral sensory thalamus and cortex has not been determined. We therefore examined the distribution of CGRP-like immunoreactive (CGRPir) innervation of the insular cortex and the parvicellular division of the ventroposterior nucleus of the thalamus (VPpc) in the rat by using immunohistochemistry for CGRP combined with retrograde transport of the fluorescent dye fluoro-gold. Modest numbers of CGRPir fibers were distributed in the dysgranular and agranular insular cortex, but few were observed in the granular insular cortex. The density of CGRPir innervation increased caudally along the rhinal fissue and was considerably greater in the perirhinal cortex. When fluoro-gold was injected into the insular cortex numerous retrogradely labeled neurons were seen in the VPpc, but few of these were CGRPir. Retrogradely labeled CGRPir neurons were, however, seen in the ventral lateral and medial parabrachial (PB) subnuclei. Injection of fluoro-gold into the perirhinal cortex (which is just caudal to the insular cortex along the rhinal fissure) resulted in many retrogradely labeled CGRPir neurons in the posterior thalamic region, including the subparafascicular, the lateral subparafascicular, and the posterior intralaminar nuclei. The VPpc was heavily innervated by CGRPir fibers but contained few CGRPir cell bodies. Injection of fluoro-gold into the VPpc resulted in many retrogradely labeled CGRPir neurons in the external medial PB subnucleus bilaterally, but with a contralateral predominance. Smaller numbers of retrogradely labeled CGRPir neurons were also observed in the ventrolateral PB subnucleus, bilaterally with an ipsilateral predominance. These results suggest that CGRP may be a neuromodulator in the ascending visceral sensory pathways from the PB to the VPpc and the insular cortex, but not between the latter two structures.