Search

The nucleus retroambiguus (NRA) consists of premotor neurons in the caudal medulla. It is involved in expiration, vomiting, vocalization, and probably reproductive behavior by means of projections to distinct motoneuronal cell groups. Because no information is available about the NRA and its efferent pathways in primates, the present study examines NRA projections to the lumbosacral spinal cord in female rhesus monkeys. To identify the NRA, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected into the lumbosacral cord in three monkeys. To study the distribution of NRA axons in the lumbosacral cord, WGA-HRP injections were made into the NRA in seven monkeys. To identify motoneuronal cell groups receiving input from the NRA, the same seven monkeys also received cholera toxin subunit b (CTb) injections into different hindlimb, axial, and pelvic floor muscles. The results show that NRA neurons projecting to the lumbosacral cord are mainly located between 1 to 4 mm caudal to the obex. They send numerous axons to external oblique and pelvic floor motoneurons, whereas projections to iliopsoas and axial motoneurons are less numerous. The projections are bilateral, but show a clear contralateral predominance in the iliopsoas, axial, and pelvic floor motoneuronal cell groups. At the ultrastructural level, NRA-terminal profiles make asymmetrical contacts with labeled and unlabeled dendrites in these motoneuronal cell groups and contain large amounts of spherical and a few dense core vesicles. It is concluded that the NRA is well developed in the monkey and that there exists a direct pathway from the NRA to lumbosacral motoneurons in this species. The finding that the NRA projects to a somewhat different set of motoneuronal cell groups compared with other species fits the concept that it is not only involved in expiration-related activities but also in species specific receptive and submissive behavior. J. Comp. Neurol. 424: 233-250, 2000. (C) 2000 Wiley-Liss, Inc.

Reproductive behavior in most mammalian species consists of a highly stereotyped pattern of movements, is elicited by specific sensory stimuli and is sex steroid dependent. The present paper describes a concept of the pathways in the midbrain, brainstem and spinal cord which control the receptive posture of the female cat. The midbrain periaqueductal gray (PAG), which is an important structure in the Emotional Motor System (EMS), receives direct input from a distinct group of neurons in the dorsal horn of the lumbosacral cord. This cell group overlaps with the location of pelvic and to lesser extent, pudendal nerve primary efferents, which convey information from the pelvic viscera and sex organs to the central nervous system. The FAG, in turn, controls various motor components of female receptive behavior using different pathways. For example, immobility, which is one of the characteristics of receptive behavior, might be mediated by a diffuse pathway from the FAG, via the ventral part of the medial medullary tegmentum, to all parts of the spinal ventral hem. More specific components, such as hindlimb treading, lateral deviation of the tail and elevation of the lower back, are thought to be controlled by a circumscribed projection from the FAG to the nucleus retroambiguus (NRA). The NRA is a group of interneurons at the transition between brainstem and spinal cord and projects directly to distinct lumbosacral motoneuronal cell groups, which innervate muscles that are likely to be involved in the female receptive posture. Estrogen induces axonal sprouting of the NRA-lumbosacral pathway in adult female cats, which explains why female cats only display receptive behavior when estrogen levels are high. (C) 1998 Elsevier Science B.V. All rights reserved.

Reproductive behavior in most mammalian species consists of a highly stereotyped pattern of movements, is elicited by specific sensory stimuli and is sex steroid dependent. The present paper describes a concept of the pathways in the midbrain, brainstem and spinal cord which control the receptive posture of the female cat. The midbrain periaqueductal gray (PAG), which is an important structure in the Emotional Motor System (EMS), receives direct input from a distinct group of neurons in the dorsal horn of the lumbosacral cord. This cell group overlaps with the location of pelvic and to lesser extent, pudendal nerve primary efferents, which convey information from the pelvic viscera and sex organs to the central nervous system. The FAG, in turn, controls various motor components of female receptive behavior using different pathways. For example, immobility, which is one of the characteristics of receptive behavior, might be mediated by a diffuse pathway from the FAG, via the ventral part of the medial medullary tegmentum, to all parts of the spinal ventral hem. More specific components, such as hindlimb treading, lateral deviation of the tail and elevation of the lower back, are thought to be controlled by a circumscribed projection from the FAG to the nucleus retroambiguus (NRA). The NRA is a group of interneurons at the transition between brainstem and spinal cord and projects directly to distinct lumbosacral motoneuronal cell groups, which innervate muscles that are likely to be involved in the female receptive posture. Estrogen induces axonal sprouting of the NRA-lumbosacral pathway in adult female cats, which explains why female cats only display receptive behavior when estrogen levels are high. (C) 1998 Elsevier Science B.V. All rights reserved.

In 1995, we discovered a new pathway in the cat, which originates from the nucleus retroambiguus (NRA) and terminates in a distinct set of lumbosacral hindlimb, axial, and pelvic floor motoneuronal cell groups [VanderHorst VG.JM, Holstege G (1995) Caudal medullary pathways to lumbosacral motoneuronal cell groups in the cat: evidence for direct projections possibly representing the final common pathway for lordosis. J Comp Neurol 359:457-475]. The NRA is a compact group of interneurons located laterally in the caudal medulla oblongata. Its projection to lumbosacral moloneurons is thought to represent the final common pathway for male mounting and for female receptive or lordosis behavior. However, females only display lordosis behavior when they are in estrus, which suggests that the NRA-lumbosacral pathway is only active during estrus. This raised the question of whether estrogen affects this pathway. The effect of estrogen on the NRA-lumbosacral projection was studied light microscopically, using wheat-germ agglutinin horseradish peroxidase (WGA-HRP) as a tracer. The rubrospinal pathway served as control. The density of labeled NRA fibers in their target hindlimb motoneuronal cell groups appeared abundant in estrous and very weak in nonestrous cats. Such differences were not found in the rubrospinal pathway. For electron microscopical study, the NRA projection to the semimembranosus motoneuronal cell group was selected. In this cell group, an almost ninefold increase of labeled profiles was found in estrous versus nonestrous cats. Moreover, the semimembranous motoneuronal cell group contained labeled growth cones in estrous, but not in nonestrous, cats. The present study is the first to show that estrogen induces axonal outgrowth of a precisely identified pathway in the adult mammalian central nervous system. The possible mechanisms underlying this outgrowth are discussed.

The nucleus retroambiguus (NRA) in the caudal medulla oblongata plays a role in expiration, vocalization, vomiting, and possibly lordosis. The present study tried to determine which structures, in turn, control the NRA. One cell group is the periaqueductal gray (FAG), which is considered to be the final integrator of defensive and aggressive behaviors, micturition, vocalization, and lordosis. Structures rostral to the FAG seem to bypass the NRA. With respect to the existence of cell groups caudal to the FAG projecting to the NRA, the situation is less clear.Therefore, in five adult female cats, injections of wheat germ agglutinin-horseradish peroxidase were centered on the NRA, and the resulting retrogradely labeled neurons were plotted. In the areas containing retrogradely labeled cells, the anterograde autoradiographic tracer [H-3]-leucine was injected in 66 cats.The combined results demonstrated that-NRA afferents not only originate from the FAG but also from specific cell groups in the pontine and medullary lateral tegmental field, i.e., the ventrolateral parabrachial nucleus, the nucleus Kolliker-Fuse, the retrotrapezoid nucleus, and the ventrolateral part of the medulla caudal to the facial nucleus including the Botzinger and pre-Botzinger complex and the periambigual region. Afferents also originate from the solitary nucleus and two cell groups in the ventral part of the medullary medial tegmental field, one at the level of facial nucleus and one just rostral to the hypoglossal nucleus.It can be concluded that many respiratory-related cell groups have direct access to the NRA. The cell groups in the medial tegmental field, which have not yet been found to play an important role in respiration, might-serve as relay for certain limbic system cell groups to reach the NRA in the context of specific emotional behavior. (C) 1996 Wiley-Liss, Inc.

The vertebrate dorsal mesencephalon consists of the superior colliculus, the dorsal portion of the periaqueductal gray, and the mesencephalic trigeminal neurons in between. These structures, via their descending pathways, take part in various behavioral responses to environmental stimuli. This study was undertaken to compare the origins and trajectories of these pathways in the cat. Injections of horseradish peroxidase into the cervical spinal cord and upper medullary medial tegmentum retrogradely labeled cells mainly in the contralateral intermediate and deep superior colliculus, and in the ipsilateral dorsal and lateral periaqueductal gray and adjacent tegmentum. Only injections in the medullary lateral tegmental field labeled mesencephalic trigeminal neurons ipsilaterally. Autoradiographic tracing results, based on injections across the dorsal mesencephalon, revealed three efferent fiberstreams. A massive first fiberstream (limbic pathway), consisting of thin fibers, descended ipsilaterally from the dorsal and lateral periaqueductal gray and adjacent superior colliculus through the mesencephalic and pontine lateral tegmentum, terminating in these areas as well as in the ventral third of the caudal pontine and medullary medial tegmentum. A few fibers from the dorsal periaqueductal gray matter (PAG) were distributed bilaterally to the dorsal vagal, solitary, and retroambiguus nuclei. The second fiberstream (the predorsal bundle) descended contralaterally from the superior colliculus (SC) and consisted of both thick and thin labeled fibers. The thin fibers terminated bilaterally in the dorsomedial nucleus reticularis tegmenti pontis and the medial half of the caudal medial accessory inferior olive. The thick fibers targeted the contralateral dorsal two thirds of the caudal pontine and medullary medial tegmental fields, and the facial, abducens, lateral reticular, subtrigeminal, and prepositus hypoglossi nuclei. A few fibers recrossed the midline to terminate in the ipsilateral medial tegmentum. Caudal to the obex, fibers terminated laterally in the tegmentum and upper cervical intermediate zone. From the lateral SC, fibers terminated bilaterally in the lateral tegmental fields of the pons and medulla and lateral facial subnuclei. The third fiberstream (mesencephalic trigeminal or Probst tract) terminated in the supratrigeminal and motor trigeminal nuclei, and laterally in the tegmentum and upper cervical intermediate zone. In summary, neurons in the PAG and in the deep layers of the SC give rise to a massive ipsilateral descending pathway, in which a medial-to-lateral organization exists. A similar topographical pattern occurs in the crossed SC projections. The possibility that these completely different descending systems cooperate in producing specific defensive behaviors is discussed.

The efferent connections of the rostral parvocellular reticular formation to pontine and medullary nuclei in the rat were studied with anterogradely transported Phaseolus vulgaris leucoagglutinin. Dense innervations from the rostral parvocellular reticular formation were found in the mesencephalic trigeminal nucleus, the supratrigeminal area, the motor trigeminal nucleus, the motor trigeminal nucleus, the facial, hypoglossal and parabrachial nuclei and specific parts of the caudal parvocellular reticular formation, including nucleus linearis and the dorsal reticular nucleus of the medulla. The raphe nuclei, nucleus of the solitary tract, inferior olive, dorsal principal sensory, spinal trigeminal nuclei and gigantocellular reticular nucleus and the ventral reticular nucleus of the medulla received moderate projections. In general, the projections from the rostral parvocellular reticular formation were bilateral with an ipsilateral dominance. The dorsal motor vagus and the ambiguus nuclei were not labeled. It is concluded that the rostral parvocellular reticular formation participates in regulation of orofacial motor control and in neural networks for limbic control of metabolic homeostasis.

Recently, in the female cat, nucleus retroambiguus (NRA) projections have been described as distinct motoneuronal cell groups in the lumbar enlargement, possibly involved in lordosis behavior. The present study deals with the NRA-lumbosacral pathway in the male cat, Lumbosacral injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were made to localize and quantify retrogradely labeled neurons in the caudal medulla. These injections were preceded by spinal hemisections to distinguish between neurons with ipsi- and contralaterally descending axons. The NRA-lumbosacral fibers descended almost exclusively contralaterally, but neurons in areas surrounding the NRA projected mainly ipsilaterally. Injections of WGA-HRP were made in the region of the NRA to determine its targets in the lumbosacral cord. To distinguish between the contralateral NRA pathways and the ipsilateral projections from neurons in the adjoining lateral tegmentum, the injections were preceded by ipsilateral hemisections in C2. A new scaling method was used to compare the results of the different cases, despite variations in size and segmental organization. The results show that the distribution pattern of anterogradely labeled fibers in the lumbosacral cord matched precisely the location of certain motoneuronal cell groups. The NRA projected densely to the abdominal wall and pelvic floor motoneurons in Onuf's nucleus, moderately to adductor longus, semimembranosus, and biceps femoris anterior motoneuronal cell groups, and only sparsely to iliopsoas and semitendinosus motoneuronal cell groups. Compared with the findings in the female, the NRA in the male cat projects more heavily to the biceps anterior and adductor longus and only sparsely to the iliopsoas and semitendinosus motoneuronal cell groups. These male-female differences are discussed. (C) 1997 Wiley-Liss. Inc.

In 1995, we discovered a new pathway in the cat, which originates from the nucleus retroambiguus (NRA) and terminates in a distinct set of lumbosacral hindlimb, axial, and pelvic floor motoneuronal cell groups [VanderHorst VGJM, Holstege G (1995) Caudal medullary pathways to lumbosacral motoneuronal cell groups in the cat: evidence for direct projections possibly representing the final common pathway for lordosis. J Comp Neurol 359:457-475]. The NRA is a compact group of interneurons located laterally in the caudal medulla oblongata. Its projection to lumbosacral motoneurons is thought to represent the final common pathway for male mounting and for female receptive or lordosis behavior. However, females only display lordosis behavior. However, females only display lordosis behavior when they are in estrus, which suggests that the NRA-lumbosacral pathway is only active during estrus. This raised the question of whether estrogen affects this pathway. The effect of estrogen on the NRA-lumbosacral projection was studied light microscopically, using wheat-germ agglutinin horseradish peroxidase (WGA-HRP) as a tracer. The rubrospinal pathway served as control. The density of labeled NRA fibers in their target hindlimb motoneuronal cell groups appeared abundant in estrous and very weak in nonestrous cats. Such differences were not found in the rubrospinal pathway. For electron microscopical study, the NRA projection to the semi-membranosus motoneuronal cell group was selected. In this cell group, an almost ninefold increase of labeled profiles was found in estrous versus nonestrous cats. Moreover, the semimembranous motoneuronal cell group contained labeled growth cones in estrous, but not in nonestrous, cats. The present study is the first to show that estrogen induces axonal outgrowth of a precisely identified pathway in the adult mammalian central nervous system. The possible mechanisms underlying this outgrowth are discussed.

The nucleus retroambiguus (NRA) in the caudal medulla oblongata plays a role in expiration, vocalization, vomiting, and possibly lordosis. The present study tried to determine which structures, in turn, control the NRA. One cell group is the periaqueductal gray (FAG), which is considered to be the final integrator of defensive and aggressive behaviors, micturition, vocalization, and lordosis. Structures rostral to the FAG seem to bypass the NRA. With respect to the existence of cell groups caudal to the FAG projecting to the NRA, the situation is less clear. Therefore, in five adult female cats, injections of wheat germ agglutinin-horseradish peroxidase were centered on the NRA, and the resulting retrogradely labeled neurons were plotted. In the areas containing retrogradely labeled cells, the anterograde autoradiographic tracer [H-3]-leucine was injected in 66 cats. The combined results demonstrated that-NRA afferents not only originate from the FAG but also from specific cell groups in the pontine and medullary lateral tegmental field, i.e., the ventrolateral parabrachial nucleus, the nucleus Kolliker-Fuse, the retrotrapezoid nucleus, and the ventrolateral part of the medulla caudal to the facial nucleus including the Botzinger and pre-Botzinger complex and the periambigual region. Afferents also originate from the solitary nucleus and two cell groups in the ventral part of the medullary medial tegmental field, one at the level of facial nucleus and one just rostral to the hypoglossal nucleus. It can be concluded that many respiratory-related cell groups have direct access to the NRA. The cell groups in the medial tegmental field, which have not yet been found to play an important role in respiration, might-serve as relay for certain limbic system cell groups to reach the NRA in the context of specific emotional behavior. (C) 1996 Wiley-Liss, Inc.

The nucleus retroambiguus (NRA) projects to distinct brainstem and cervical and thoracic cord motoneuronal cell groups. The present paper describes NRA projections to distinct motoneuronal cell groups in the lumbar enlargement. Lumbosacral injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were made to localize and quantify the retrogradely labeled neurons in the caudal medullary lateral tegmentum. These injections were combined with spinal hemisections to distinguish between neurons having ipsi- or contralaterally descending axons. The NRA-lumbosacral fibers descend almost exclusively contralaterally, but neurons in areas surrounding the NRA project mainly ipsilaterally.In an anterograde tracing study, injections of WGA-HRP or tritiated leucine were made in the region of the NRA to determine the NRA. targets in the lumbosacral cord. Hemisections in C2 made it possible to distinguish between NRA projections and projections from neurons in the adjoining lateral tegmentum. The results show delicate NRA projections to distinct lumbosacral motoneuronal cell groups innervating specific hindlimb muscles (iliopsoas, adductors, and hamstrings) as well as axial muscles (medial longissimus and proximal tail muscles). The projection is bilateral, with a contralateral predominance. Ipsilaterally terminating fibers are derived from NRA neurons whose axons cross the midline at the level of the obex, descend through the contralateral spinal white matter, and recross at the level of termination. A conceptual description is presented in which the periaqueductal gray-NRA-lumbosacral projections form the final common pathway for lordosis in the cat. (C) 1995 Wiley-Liss, Inc.

The vertebrate dorsal mesencephalon consists of the superior colliculus, the dorsal portion of the periaqueductal gray, and the mesencephalic trigeminal neurons in between. These structures, via their descending pathways, take part in various behavioral responses to environmental stimuli. This study was undertaken to compare the origins and trajectories of these pathways in the cat. Injections of horseradish peroxidase into the cervical spinal cord and upper medullary medial tegmentum retrogradely labeled cells mainly in the contralateral intermediate and deep superior colliculus, and in the ipsilateral dorsal and lateral periaqueductal gray and adjacent tegmentum. Only injections in the medullary lateral tegmental field labeled mesencephalic trigeminal neurons ipsilaterally. Autoradiographic tracing results, based on injections across the dorsal mesencephalon, revealed three efferent fiberstreams. A massive first fiberstream (limbic pathway), consisting of thin fibers, descended ipsilaterally from the dorsal and lateral periaqueductal gray and adjacent superior colliculus through the mesencephalic and pontine lateral tegmentum, terminating in these areas as well as in the ventral third of the caudal pontine and medullary medial tegmentum. A few fibers from the dorsal periaqueductal gray matter (PAG) were distributed bilaterally to the dorsal vagal, solitary, and retroambiguus nuclei. The second fiberstream (the predorsal bundle) descended contralaterally from the superior colliculus (SC) and consisted of both thick and thin labeled fibers. The thin fibers terminated bilaterally in the dorsomedial nucleus reticularis tegmenti pontis and the medial half of the caudal medial accessory inferior olive. The thick fibers targeted the contralateral dorsal two thirds of the caudal pontine and medullary medial tegmental fields, and the facial, abducens, lateral reticular, subtrigeminal, and prepositus hypoglossi nuclei. A few fibers recrossed the midline to terminate in the ipsilateral medial tegmentum. Caudal to the obex, fibers terminated laterally in the tegmentum and upper cervical intermediate zone. From the lateral SC, fibers terminated bilaterally in the lateral tegmental fields of the pons and medulla and lateral facial subnuclei. The third fiberstream (mesencephalic trigeminal or Probst tract) terminated in the supratrigeminal and motor trigeminal nuclei, and laterally in the tegmentum and upper cervical intermediate zone. In summary, neurons in the PAG and in the deep layers of the SC give rise to a massive ipsilateral descending pathway, in which a medial-to-lateral organization exists. A similar topographical pattern occurs in the crossed SC projections. The possibility that these completely different descending systems cooperate in producing specific defensive behaviors is discussed.