Neuroanatomical and neurochemical organization of projections from the central amygdaloid nucleus to the nucleus retroambiguus via the periaqueductal gray in the rat

The periaqueductal gray (PAG)-nucleus retroambiguus (NRA) pathway has been known to be involved in the control of vocalization and sexual behavior. To know how the amygdaloid complex influences the PAG-NRA pathway, here we first examined the synaptic organization between the central amygdaloid nucleus (CeA) fibers and the PAG neurons that project to the NRA by using anterograde and retrograde tract-tracing techniques in the rat. After ipsilateral injections of biotinylated dextran amine (BDA) into the CeA and cholera toxin B subunit (CTb) into the NRA, the prominent overlapping distribution of BDA-labeled axon terminals and CTb-labeled neurons was found ipsilaterally in the lateral/ventrolateral PAG, where some of the BDA-labeled terminals made symmetrical synaptic contacts with somata and dendrites of the CTb-labeled neurons. After CTb injection into the lateral/ventrolateral PAG, CTb-labeled neurons were distributed mainly in the medial division of the CeA. After BDA injection into the lateral/ventrolateral PAG, BDA-labeled fibers were distributed mainly in and around the NRA within the medulla oblongata. Using a combined retrograde tracing and in situ hybridization technique, we further demonstrated that more than half of the CeA neurons labeled with Fluoro-Gold (FG) injected into the lateral/ventrolateral PAG were positive for glutamic acid decarboxylase 67 mRNA and that the vast majority of PAG neurons labeled with FG injected into the NRA expressed vesicular glutamate transporter 2 mRNA. The present results suggest that the glutamatergic PAG-NRA pathway is under the inhibitory influence of the GABAergic CeA neurons.     

The organization of afferent projections to the midbrain periaqueductal gray of the rat

The retrograde transport technique was utilized in the present study to investigate the afferent projections to the periaqueductal gray of the rat. Iontophoretic injections of horseradish peroxidase were made into the periaqueductal gray of 22 experimental animals and into regions adjacent to the periaqueductal gray in 6 control animals. Utilization of the retrograde transport method permitted a quantitative analysis of the afferent projections not only to the entire periaqueductal gray, but also to each of its four intrinsic subdivisions. The largest cortical input to this midbrain region arises from areas 24 and 32 in the medial prefrontal cortex. The basal forebrain provides a significant input to the periaqueductal gray and this arises predominantly from the ipsilateral lateral and medial preoptic areas and from the horizontal limb of the diagonal band of Broca. The hypothalamus was found to provide the largest descending input to the central gray. Numerous labeled cells occurred in the ventromedial hypothalamic nucleus, the lateral hypothalamic area, the posterior hypothalamic area, the anterior hypothalamic area, the perifornical nucleus and the area of the tuber cinereum. The largest mesencephalic input to the periaqueductal gray arises from the nucleus cuneiformis and the substantia nigra. The periaqueductal gray was found to have numerous intrinsic connections and contained a significant number of labeled cells both above and below the injection site in each case. Other structures containing significant label in the midbrain and isthmus region included the nucleus subcuneiformis, the ventral tegmental area, the locus coeruleus and the parabrachial nuclei. The medullary and pontine reticular formation provide the largest input to the periaqueductal gray from the lower brain stem. The midline raphe magnus and superior central nucleus also supply a significant fiber projection to the central gray. Both the trigeminal complex and the spinal cord provide a minor input to this region of the midbrain.The sources of afferent projections to the periaqueductal gray are extensive and allow this midbrain region to be influenced by motor, sensory and limbic structures. In addition, evidence is provided which indicates that the four subdivisions of the central gray receive differential projections from the brain stem as well as from higher brain structures.     

The organization of dorsal medullary projections to the central amygdaloid nucleus and parabrachial nuclei in the rabbit

The amygdaloid central nucleus and the pontine parabrachial nucleus receive direct, ascending projections from autonomic regulatory nuclei of the dorsal medulla and are recognized as important components of a forebrain system which contributes to autonomic regulation. The present study was designed to provide more detailed information on the anatomical organization of this ascending system in the rabbit by determining (a) the extent to which separate populations of neurons within the solitary complex project to the central nucleus and parabrachial nucleus, (b) the topographical distribution of the projections of the solitary complex within the amygdaloid central nucleus and parabrachial nucleus and (c) the extent to which projections from the solitary complex to the parabrachial nucleus terminate in the region of origin of projections from the parabrachial nucleus to the amygdaloid central nucleus.

A fluorescent dye, double retrograde-labeling technique demonstrated that separate populations of neurons in the solitary complex projected to the amygdaloid central nucleus and parabrachial nucleus. Neurons of both populations were more heavily concentrated within the caudal two thirds of nucleus of the solitary tract and were most numerous within the commissural, medial and dorsomedial subnuclei. Labeled neurons were also located within the dorsal motor nucleus of the vagus nerve. Autoradiographic experiments demonstrated that injections of amino acids into the solitary complex resulted in terminal labeling in the central nucleus. This labeling extended rostrally into the adjacent sublenticular substantia innominata and lateral component of the bed nucleus of the stria terminalis. Label was also observed within the lateral, medial, and Kolliker-Fuse regions of the parabrachial nucleus. A particularly dense field was observed overlying cells located within the ventrolateral region of the lateral parabrachial nucleus. This region contained the majority of labeled neurons within the parabrachial nucleus following fluorescent dye injections into the central nucleus. Furthermore, injections of amino acids into this region resulted in terminal labeling within the central nucleus, with a particularly dense area observed within the medial aspect of the nucleus.

The results demonstrate that separate populations of neurons within the solitary complex of the rabbit project to the central amygdaloid and parabrachial nuclei and that the majority of these are located within the caudal two-thirds of the complex. Furthermore, the results suggest that the solitary complex projects both directly and indirectly, primarily via the lateral parabrachial nucleus, to the central amygdaloid nucleus. These projections offer an anatomical substrate by which visceral afferent information may influence the limbic forebrain.     

Frontal cortex projections to the amygdaloid central nucleus in the rabbit

Evidence has recently been presented which demonstrates that the amygdaloid central nucleus projects directly upon cardiovascular/autonomic regulatory nuclei of the dorsal medulla and that in the rabbit this nucleus may influence cardiovascular activity during emotional states. The present study is one of a series of investigations designed to provide information on the innervation of the central nucleus in the rabbit and describes the topography and origin of frontal cortex projections to the nucleus based upon retrograde and anterograde axonal transport techniques. Injections of horseradish peroxidase or the fluorescent dyes, Bisbenzimide or Nuclear Yellow, into the central nucleus resulted in abundant numbers of retrogradely labeled neurons in three regions of the frontal cortex: the insular cortex on the lateral surface and areas 25 and 32 on the medial surface of the hemisphere. The majority of labeled neurons in the insular cortex were located in layer V of the dorsal and posterior agranular insular regions, although labeled neurons were observed in layer V of the granular insular cortex as well as in layers II and III of the posterior agranular insular cortex. Labeled neurons in areas 25 and 32 were located throughout all layers and the total number of these neurons was substantially less than that observed in the insular cortex. Autoradiographic experiments in which amino acids were injected into the insular cortex resulted in a dense pattern of transported label within the central nucleus that extended rostrally into the sublenticular substantia innominata and lateral component of the bed nucleus of the stria terminalis. Label was also observed in the cortical, lateral, basolateral and basomedial amygdaloid nuclei. In contrast to the projections from the insular cortex, amino acid injections into areas 25 and 32 resulted in only relatively light labeling within the most rostral region of the central nucleus; otherwise the nucleus was partially encapsulated and virtually devoid of label. These results suggest that the insular cortex possesses the potential to directly influence the central nucleus projection to cardiovascular/autonomic regulatory nuclei of the dorsal medulla and thus, together with the amygdaloid central nucleus, appears to be an important component of a forebrain system involved in cardiovascular/autonomic regulation.     

A disynaptic pathway from the central amygdaloid nucleus to the paraventricular hypothalamic nucleus via the parastrial nucleus in the rat

The organization of projections from the central amygdaloid nucleus (CeA) to the paraventricuilar hypothalamic nucleus (PVH) has been studied in order to understand the anatomical substrates of amygdaloid modulation of endocrine and autonomic functions, and a hypothesis that the bed nucleus of the stria terminalis (BST) may act as a relay site between the CeA and PVH has been proposed. Using anterograde and retrograde tract-tracing methods, in the rat, we first indicated that neurons in the parastrial nucleus (PS), where projection fibers from the central amygdaloid nucleus (CeA) terminated, sent their axons to the paraventricular hypothalamic nucleus (PVH). We further demonstrated that the CeA terminals formed symmetrical synaptic contacts with somata and dendrites of the PVH-projecting PS neurons, and that the PS received CeA fibers predominantly from the lateral part and sent large numbers of projection fibers to almost all the subdivisions of the PVH. Using anterograde tracing combined with the postembedding immunogold method, we finally revealed that nearly all the CeA terminals in the PS were immunoreactive for gamma-aminobutyric acid. The present data suggest that output signals from the CeA are transmitted disynaptically to the PVH neurons via the PS neurons and modulate PVH neuron activity by way of disinhibition.     

Serotonin-, substance P- or leucine-enkephalin-containing neurons in the midbrain periaqueductal gray and nucleus raphe dorsalis send projection fibers to the central amygdaloid nucleus in the rat.

By a double-labeling method combining the retrograde tracing of horseradish peroxidase and the immunocytochemical technique, serotonin-, substance P- or leucine-enkephalin-like immunoreactive neurons in the midbrain periaqueductal gray (PAG) and the nucleus raphe dorsalis (DR) of the rat were found to send projection fibers to the central amygdaloid nucleus bilaterally with an ipsilateral dominance. These PAG neurons were chiefly distributed in the ventrolateral PAG subdivision and the ventral parts of medial PAG subdivision at the middle and caudal levels of PAG.     

Fluorescent double-label study of lateral reticular nucleus projections to the spinal cord and periaqueductal gray in the rat.

Following injections of WGA-HRP into either the spinal cord or periaqueductal gray, labeled neurons were observed bilaterally along the periphery of the lateral reticular nucleus (LRN) magnocellular division. The possibility that some of these neurons in the LRN provide collateral axonal branches to both the periaqueductal gray and the spinal cord was investigated in rats using a retrograde double-labeling method employing two different fluorescent tracers, True Blue and Nuclear Yellow. Following sequential injection of the two fluorescent axonal tracers into the spinal cord and periaqueductal gray in the same animal, a modest number of double-labeled neurons were observed bilaterally near the medial and dorsal perimeter of the magnocellular division of the LRN. The labeled neurons were distinctly multipolar in shape and measured approximately 15-18 mu in their greatest transverse diameter. No double-labeled neurons were observed in the parvocellular or subtrigeminal divisions of the LRN. Based upon these observations, it is suggested that collaterals of the LRN-spinal pathway provide feedback information to the periaqueductal gray that might then be used to modulate the participation of the latter cell group in a variety of pain processing and cardiovascular regulatory functions.     

Collateral projections from the midbrain periaqueductal gray to the nucleus raphe magnus and nucleus accumbens in the rat. A fluorescent retrograde double-labelling study.

Collateral projections of single neurons in the midbrain periaqueductal gray (PAG) to the nucleus accumbens (ACB) and nucleus raphe magnus (NRM) were observed in the rat by a fluorescent retrograde double-labelling technique. After injecting propidium iodide into the ACB and bisbenzimide into the NRM, doubly labelled PAG neurons were most frequently seen in the ventrolateral subnucleus and ventral part of the medial subnucleus at the middle and caudal levels of the PAG.     

Amygdala projections to central amygdaloid nucleus subdivisions and transition zones in the primate

In rats and primates, the central nucleus of the amygdala (CeN) is most known for its role in responses to fear stimuli. Recent evidence also shows that the CeN is required for directing attention and behaviors when the salience of competing stimuli is in flux. To examine how information flows through this key output region of the primate amygdala, we first placed small injections of retrograde tracers into the subdivisions of the central nucleus in Old world primates, and examined inputs from specific amygdaloid nuclei. The amygdalostriatal area and interstitial nucleus of the posterior limb of the anterior commissure (IPAC) were distinguished from the CeN using histochemical markers, and projections to these regions were also described. As expected, the basal nucleus and accessory basal nucleus are the main afferent connections of the central nucleus and transition zones. The medial subdivision of the central nucleus (CeM) receives a significantly stronger input from all regions compared to the lateral core subdivision (CeLcn). The corticoamygdaloid transition zone (a zone of confluence of the medial parvicellular basal nucleus, paralaminar nucleus, and the sulcal periamygdaloid cortex) provides the main input to the CeLcn. The IPAC and amygdalostriatal area can be divided in medial and lateral subregions, and receive input from the basal and accessory basal nucleus, with differential inputs according to subdivision. The piriform cortex and lateral nucleus, two important sensory interfaces, send projections to the transition zones. In sum, the CeM receives broad inputs from the entire amygdala, whereas the CeLcn receives more restricted inputs from the relatively undifferentiated corticoamygdaloid transition region. Like the CeN, the transition zones receive most of their input from the basal nucleus and accessory basal nucleus, however, inputs from the piriform cortex and lateral nucleus, and a lack of input from the parvicellular accessory basal nucleus, are distinguishing afferent features.     

Neuroanatomical study of afferent projections to the supramammillary nucleus of the rat

We examined the regions projecting to the supramammillary nucleus of the rat with retrograde transport of WGA-HRP and WGA, and anterograde transport of Phaseolus vulgaris leucoagglutinin. The supramammillary nucleus receives major descending afferents from the infralimbic cortex, the dorsal peduncular cortex, the nucleus of the diagonal band of Broca, the medial and lateral preoptic nuclei, bilaterally. The major ascending afferents come from the pars compacta of the nucleus centralis superior, the ventral tegmental nucleus, and the laterodorsal tegmental nucleus. The supramammillary nucleus also receives a few (but distinct) fibers from the anterior and lateral hypothalamic nuclei, the ventral premammillary nucleus, the interpeduncular nucleus, the cuneiform nucleus, the dorsal raphe nucleus, the incertus nucleus, and the C3 region including the prepositus hypoglossi nucleus. All descending fibers run through the medial forebrain bundle. Almost all ascending fibers from the pars compacta of the nucleus centralis superior and the laterodorsal tegmental nucleus run through the mammillary peduncle, and terminate throughout the supramammillary nucleus. A few fibers from the laterodorsal tegmental nucleus and the C3 region run through the fasciculus longitudinalis dorsalis and terminate in the dorsal part of the supramammillary nucleus including the supramammillary decussation.Abbreviations a anterior commissure - AC accumbens nucleus - AR arcuate nucleus - BS bed nucleus of the stria terminalis - C3 C3 adrenergic region - CA interstitial nucleus of Cajal - CC pars compacta of the nucleus centralis superior - CS nucleus centralis superior - CU cuneiform nucleus - CX cingulate cortex - DB nucleus of the diagonal band of Broca - DH dorsomedial hypothalamic nucleus - ds decussation of the superior cerebellar peduncle - DX dorsal peduncular cortex - f fornix - fld fasciculus longitudinalis dorsalis - flm fasciculus longitudinalis medialis - IN incertus nucleus - IX infralimbic cortex - LC nucleus of the locus ceruleus - le lemniscus medialis - LH lateral hypothalamic nucleus - LM lateral mammillary nucleus - LO lateral preoptic nucleus - LS lateral septal nucleus - LT laterodorsal tegmental nucleus - mfb medial forebrain bundle - MM medial mammillary nucleus - MO medial preoptic nucleus - mp mammillary peduncle - mt mammillothalamic tract - MV medial vestibular nucleus - PD dorsal premammillary nucleus - PH prepositus hypoglossi nucleus - PV ventral premammillary nucleus - RD dorsal raphe nucleus - rf fasciculus retroflexus - SUM supramammillary nucleus - sx supramammillary decussation - T tenia tecta - TD dorsal tegmental nucleus - TM tuberomammillary nucleus - TV ventral tegmental nucleus - VT ventral tegmental area of Tsai     

Afferent projections to the periaqueductal gray in the rabbit

The afferents to the periaqueductal gray in the rabbit have been described following hydraulic pressure injection of horseradish peroxidase at various sites throughout this structure. Every third section was reacted with tetramethylbenzidine, for the localization of afferent neurons. At the site of the deposit alternate sections were reacted with tetramethylbenzidine, Hanker-Yates reagent, or diaminobenzidine, for comparative assessment of the injection site. A large number of retrogradely labelled cells, assessed by bright- and dark-field microscopy, were observed in a wide range of areas throughout the brain. Major labelled areas within the telencephalon were cortical areas 5, 20, 21, 32 and 40. Within the diencephalon, the hypothalamus contained quantitatively by far the largest number of labelled cells. Of these nuclei, the dorsal pre-mammillary nucleus contained the largest number of labelled cells. Considerable labelling was also found within medial and lateral preoptic nuclei, anterior hypothalamic area, and ventromedial hypothalamic nucleus. Another diencephalic region containing a significant number of retrogradely labelled neurons was the zona incerta. At midbrain, pontine and medullary levels, additional labelled regions were: the substantia nigra, cuneiform nucleus, parabigeminal nucleus, raphe magnus, and reticular areas. Heavy labelling was seen within the periaqueductal gray itself, rostral and caudal to deposits placed within each subdivision. In addition, a large number of other areas labelled throughout the brain (Tables 2A-D). Not only were some differences noted in the pattern of labelled cells with deposits placed rostrally or caudally within periaqueductal gray, but certain topographical differences with respect to the degree of labelling within nuclei were also seen with injection sites ventral, lateral or dorsal to the aqueduct. In addition, a further difference was noted, in that over one third of the areas labelled with deposits in just one or other of the "divisions" within periaqueductal gray. The results therefore suggest that the periaqueductal gray might be divisible to some extent on the basis of connectivity with intrinsic subdivisions of the complex. It is hoped that, with time, it might prove possible to resolve any such differential input in functional terms. The wide variety of afferent input to the periaqueductal gray, and its strategic location, would seem to place it in a unique position for integrating and modifying a diversity of motor, autonomic, hormonal, sensory and limbic influences.(ABSTRACT TRUNCATED AT 400 WORDS)     

Topographical distributions of endomorphinergic pathways from nucleus tractus solitarii to periaqueductal gray in the rat

In the central nervous system (CNS), endomorphin 1 (EM1)- and endomorphin 2 (EM2)-containing neuronal cell bodies have been found in the nucleus tractus sollitarii (NTS) and the hypothalamus, and EMergic fibers and terminals are distributed widely in many regions of the CNS, including the periaqueductal gray (PAG). The aim of the present study was to examine whether EM-expressing neurons in the NTS of the rat send their axons to the PAG, and determine whether the EMergic pathway from the NTS to the PAG is topographic by using. Immunofluorescent staining for EM1 or EM2 combined with retrograde and anterograde tract-tracing methods. The results showed that after injecting tetramethyl rhodamine dextran-amine (TMR) into the ventrolateral or lateral column of the PAG, some EM1- or EM2-immunoreactive (IR) neurons in the NTS were retrogradely labeled with TMR, and the majority of the EM-IR/TMR double-labeled neurons were mainly distributed in the medial and commissural subnuclei of the NTS. Following injection of biotinylated dextran amine (BDA) into the medial or commissural subnucleus of the NTS, EM1-IR/BDA and EM2-IR/BDA double-labeled fibers and terminals were mainly distributed in the ventrolateral or lateral column of the PAG, respectively. The results indicate that EMergic pathway from the NTS to PAG is topographically organized, and suggest that EMs released from NTS to PAG projecting terminals may bind to μ-opioid receptor on the PAG neurons, and thereby contribute to various functions.     

Fluorescent double‐label study of lateral reticular nucleus projections to the spinal cord and periaqueductal gray in the rat

Following injections of WGA‐HRP into either the spinal cord or periaqueductal gray, labeled neurons were 7observed bilaterally along the periphery of the lateral reticular nucleus (LRN) magnocellular division. The possibility that some of these neurons in the LRN provide collateral axonal branches to both the periaqueductal gray and the spinal cord was investigated in rats using a retrograde double‐labeling method employing two different fluorescent tracers, True Blue and Nuclear Yellow. Following sequential injection of the two fluorescent axonal tracers into the spinal cord and periaqueductal gray in the same animal, a modest number of double‐labeled neurons were observed bilaterally near the medial and dorsal perimeter of the magnocellular division of the LRN. The labeled neurons were distinctly multipolar in shape and measured approximately 15–18 μ in their greatest transverse diameter. No double‐labeled neurons were observed in the parvocellular or subtrigeminal divisions of the LRN. Based upon these observations, it is suggested that collaterals of the LRN‐spinal pathway provide feedback information to the periaqueductal gray that might then be used to modulate the participation of the latter cell group in a variety of pain processing and cardiovascular regulatory functions. Anat Rec 256:91–98, 1999. © 1999 Wiley‐Liss, Inc.     

Direct projections from the central amygdaloid nucleus to the globus pallidus and substantia nigra in the cat.

Employing both anterograde and retrograde axonal tracing, we investigated direct projections from the central amygdaloid nucleus to the basal ganglia in the cat. The anterograde axonal tracing of Phaseolus vulgaris-leucoagglutinin revealed that projection fibers from the central amygdaloid nucleus to the basal ganglia ended in the globus pallidus (the feline homolog to the external segment of the globus pallidus of primates) and substantia nigra. The amygdalopallidal fibers terminated chiefly in the medial most part of the globus pallidus at its caudal level. The amygdalonigral fibers terminated densely in the substantia nigra pars lateralis, and moderately in the dorsolateral part of the substantia nigra pars reticulata; none of them were found to end in the substantia nigra pars compacta. Both of the amygdalopallidal and amygdalonigral projections were ipsilateral. These neuronal connections were confirmed by retrograde axonal tracing of cholera toxin B subunit in the second set of the experiments: The cells of origin of the amygdalopallidal and amygdalonigral projections were located predominantly in the lateral part of the central amygdaloid nucleus, and additionally in the intercalated cell islands of the amygdala. Most of them were of small bipolar or multipolar type. The cells projecting to the globus pallidus were preferentially distributed at the rostral levels of the central nucleus and intercalated cell islands of the amygdaloid complex, while those projecting to the substantia nigra were mainly located at the caudal levels of these amygdaloid subdivisions. In the third set of the experiments, sequential double-antigen immunofluorescence histochemistry for transported cholera toxin B subunit and horseradish peroxidase showed that some single neurons in the lateral part of the central amygdaloid nucleus, particularly at its middle level, issued axon collaterals to both the globus pallidus and substantia nigra pars lateralis. The results of the present study indicate that the central amygdaloid nucleus sends projection fibers to the globus pallidus and substantia nigra possibly to exert a limbic influence upon forebrain motor mechanisms.     

Monosynaptic projections from the nucleus retroambiguus region to laryngeal motoneurons in the rhesus monkey.

Vocalization and straining-related activities require the activation of laryngeal muscles. The control of laryngeal muscles during these activities is thought to be mediated by a pathway from the periaqueductal gray via premotor neurons in the nucleus retroambiguus to laryngeal motoneurons in the nucleus ambiguus. However, direct contacts between the nucleus retroambiguus and laryngeal motoneurons have never been demonstrated anatomically. Moreover, data in primates about the nucleus retroambiguus-nucleus ambiguus pathway are lacking. Therefore, the present study examines the projection from the nucleus retroambiguus region to laryngeal motoneurons in the rhesus monkey at the light and electron microscopic levels. Injections with wheat germ agglutinin-horseradish peroxidase were made into the nucleus retroambiguus in five rhesus monkeys to anterogradely label fibers in the nucleus ambiguus. In two of these animals, the cricothyroid muscle was injected with cholera toxin subunit b to identify the motoneurons that supply it. The results show that the nucleus retroambiguus region most densely projects to the compact formation of the nucleus ambiguus, whereas cricothyroid motoneurons, which surround the compact formation, receive a moderate projection. The projections are bilateral, with a contralateral predominance. Ultrastructurally, anterogradely labeled terminal profiles from the nucleus retroambiguus contact cholera toxin subunit b-labeled dendrites of cricothyroid motoneurons. The terminal profiles contain primarily spherical vesicles and form asymmetrical contacts with cricothyroid motoneurons.This study demonstrates that the nucleus retroambiguus region projects to the nucleus ambiguus in the primate. Some of these projections include monosynaptic connections to laryngeal motoneurons. This pathway is important for the control of the vocal folds during vocalization and straining-related activities.     

Collateralized projections from neurons in the rostral medulla to the nucleus locus coeruleus, the nucleus of the solitary tract and the periaqueductal gray.

We have examined collateral projections of locus coeruleus afferent neurons in the rostral medulla to the caudal nucleus of the solitary tract or to the periaqueductal gray using double retrograde labeling techniques in the rat. The present findings confirm previously reported connections to the locus coeruleus, the nucleus of the solitary tract and the lateral periaqueductal gray from the nucleus paragigantocellularis in the rostral ventral medulla. Our results also reveal previously unreported projections from the rostral dorsomedial medulla (in a similar region as locus coeruleus-projecting neurons) to the lateral periaqueductal gray. Following retrograde tracer injections into the nucleus of the solitary tract and the locus coeruleus, doubly labeled neurons were seen in both the nucleus paragigantocellularis and in the rostral dorsomedial medulla. Cell counts revealed that approximately 25% of locus coeruleus-projecting neurons in the nucleus paragigantocellularis, and 12% in the dorsomedial medulla, also innervate the caudal nucleus of the solitary tract. In contrast, no doubly labeled neurons within the rostral ventral medulla were found following injections into the lateral periaqueductal gray and the locus coeruleus, although singly labeled neurons for the two tracers were interdigitated in some regions. Following these injections, numerous neurons were also retrogradely labeled in the dorsomedial medulla in the region of the medial prepositus hypoglossi and the perifascicular reticular formation. A small percentage of locus coeruleus afferents in the dorsal medulla (approximately 10%) also projected to the lateral periaqueductal gray. These results indicate that neurons in both the ventrolateral and dorsomedial rostral medulla frequently send collaterals to both the locus coeruleus and the caudal nucleus of the solitary tract. A small number of neurons in the dorsomedial medulla project to both the locus coeruleus and the lateral periaqueductal gray, but separate populations of neurons project to the locus coeruleus and the lateral periaqueductal gray from the ventrolateral medulla. These results functionally link the locus coeruleus and the nucleus of the solitary tract by virtue of common afferents, and support other studies indicating the importance of central autonomic circuitry in the afferent control of locus coeruleus neurons.     

Topographical organization of amygdaloid projections to the caudatoputamen, nucleus accumbens, and related striatal-like areas of the rat brain.

The topographical organization of amygdaloid projections to the caudatoputamen, nucleus accumbens, and lateral portions of the bed nucleus of the stria terminalis and central amygdaloid nucleus was investigated, in the rat, using the retrograde transport of wheat germ agglutinin-conjugated horseradish peroxidase. Although the caudatoputamen and nucleus accumbens are the principal components of the striatum, there is evidence that lateral portions of the bed nucleus of the stria terminalis and central amygdaloid nucleus may be striatal-like structures. The basolateral nucleus was the main source of amygdaloid fibers to all of these structures. In many instances labeled areas of the basolateral nucleus were continuous with labeled areas in the adjacent lateral and basomedial nuclei. Amygdaloid neurons projecting to the striatum and striatal-like areas exhibited an overlapping topographical organization. In general, the medial-to-lateral coordinate in the striatum corresponds to the medial-to-lateral coordinate in the basolateral nucleus. There was also a partial reversed sagittal topography in that the caudal caudatoputamen receives its principal projection from the rostral basolateral nucleus. However, the rostral basolateral nucleus had a stronger projection to the rostral caudatoputamen and lateral nucleus accumbens than the caudal basolateral nucleus. The principal striatal projection of the caudal basolateral nucleus was to the medial nucleus accumbens. Amygdaloid labeling produced by injections into the medial nucleus accumbens was very similar to that seen with injections into the lateral portions of the bed nucleus of the stria terminalis and central amygdaloid nucleus. The retrograde amygdaloid labeling seen in this investigation, when compared to labeling seen with cortical injections in previous studies, suggests that specific amygdaloid domains project to particular cortical areas as well as to the principal striatal targets of the same areas.     

Efferent projections of the periaqueductal gray in the rabbit.

The efferent projections of the periaqueductal gray in the rabbit have been described by anterograde tract-tracing techniques following deposits of tritiated leucine, or horseradish peroxidase, into circumscribed sites within dorsal, lateral or ventral periaqueductal gray. No attempts were made to place labels in the fourth, extremely narrow (medial), region immediately surrounding the aqueduct whose size and disposition did not lend itself to confined placements of label within it. These anatomically distinct regions, defined in Nissl-stained sections, corresponded to the same regions into which deposits of horseradish peroxidase were made in order for us to describe afferent projections to the periaqueductal gray. In this present study distinct ascending and descending fibre projections were found throughout the brain. Terminal labelling was detected in more than 80 sites, depending somewhat upon which of the three regions of the periaqueductal gray received the deposit. Therefore, differential projections with respect to both afferent and efferent connections of these three regions of the periaqueductal gray have now been established. Ventral deposits disclosed a more impressive system of ramifying, efferent fibres than did dorsal or lateral placements of labels. With ventral deposits, ascending fibres were found to follow two major pathways from periaqueductal gray. The periventricular bundle bifurcates at the level of the posterior commissure to form hypothalamic and thalamic components which distribute to the anterior pretectal region, lateral habenulae, and nuclei of the posterior commissure, the majority of the intralaminar and midline thalamic nuclei, and to almost all of the hypothalamus. The other major ascending pathway from the periaqueductal gray takes a ventrolateral course from the deposit site through the reticular formation or, alternatively, through the deep and middle layers of the superior colliculus, to accumulate just medial to the medial geniculate body. This contingent of fibres travels more rostrally above the cerebral peduncle, distributing terminals to the substantia nigra, ventral tegmental area and parabigeminal nucleus before fanning out and turning rostrally to contribute terminals to ventral thalamus, subthalamus and zona incerta, then continuing on to supply amygdala, substantia innominata, lateral preoptic nucleus, the diagonal band of Broca and the lateral septal nucleus. Caudally directed fibres were also observed to follow two major routes. They either leave the periaqueductal gray dorsally and pass through the gray matter in the floor of the fourth ventricle towards the abducens nucleus and ventral medulla, or are directed ventrally after passing through either the inferior colliculus or parabrachial nucleus. These ventrally directed fibres merge just dorsal to the pons on the ventral surface of the brain.(ABSTRACT TRUNCATED AT 400 WORDS)