Reciprocal connections between subdivisions of the dorsal raphe and the nuclear core of the locus coeruleus in the rat

The interconnection between two brainstem monoaminergic nuclei, the dorsal raphe (DR) and the locus coeruleus (LC), was analyzed in the rat using retrograde tracing and immunocytochemistry. Gold-conjugated and inactivated wheatgerm agglutinin-horseradish peroxidase (WGA-apo-HRP-gold) was injected into subdivisions of the DR or rostro-caudal levels of the nuclear core of the LC, and labeled LC or DR neurons were identified by dopamine-beta-hydroxylase (DBH) or 5-hydroxytryptamine (5-HT) immunostaining, respectively. Within the LC-DR projection, the caudal principal LC projected to the caudal, ventromedial, and interfascicular DR. Mid-LC as well as caudal LC projected with an ipsilateral predominance to the lateral wing subdivision of the DR. A few rostral LC neurons projected to caudal, dorsomedial, and ventromedial DR. Within the DR-LC projection, the rostral LC received inputs mainly from the caudal, dorsomedial, and ventromedial DR. Mid-LC to caudal LC received projections from mid-DR to caudal DR, with the heaviest projection from the ipsilateral lateral wing as well as caudal DR. The DR-LC projection was substantially more robust than LC-DR and included both serotonergic and nonserotonergic components. Thus, the data demonstrate topographically ordered, reciprocal connectivity between DR and LC with particularly strong projections from DR to LC. Communication between these two brainstem monoaminergic nuclei may be critical for a variety of functions including sleep-wake regulation, vigilance, analgesia, cognition, and stress responses.     

Retrograde study of hypocretin-1 (orexin-A) projections to subdivisions of the dorsal raphe nucleus in the rat

A retrograde tracer, WGA-apo-HRP-gold (WG), was injected into each subdivision of the dorsal raphe (DR) nucleus, and subsequent orexin-A immunostaining was performed for the tuberal region of the hypothalamus in order to investigate orexin projections to the DR. Similar to previous studies, the majority of orexin-single-labeled neurons were observed at the dorsal half of the lateral hypothalamus (LH), the circle around the fornix, i.e., perifornical nucleus (PeF), and the area dorsal to the fornix. The present study reports that hypothalamic neurons exhibited differential projections to each subdivision of the DR. Following WG injections into rostral DR, WG-single-labeled cells were observed at the dorsal half of the LH as well as dorsomedial hypothalamic nucleus. The major input to the intermediate DR originates from the ventromedial portion of the LH, PeF, and the area dorsal to the PeF, whereas one to lateral wing DR derived from PeF as well as the ventrolateral portion of the LH. Following WG injections into caudal DR, WG-single-labeled cells were located at ventromedial LH and the ventrolateral portion of the posterior hypothalamus. Following WG injections into each DR subdivision, WG/orexin-double-labeled neurons were observed at LH, PeF, and the area dorsal to the PeF. Only a few double-labeled cells were observed in dorsomedial and posterior hypothalamic nuclei. Our observations suggest that various hypothalamic neurons differentially project to each subdivision of the DR, a portion of which is orexin-immunoreactive. These orexin-immunoreactive DR-projecting hypothalamic neurons might have wake-related influences over a variety of brain functions subject to DR efferent regulation, including affective behavior, autonomic control, nociception, cognition, and sensorimotor integration.     

Topographical organization and relationship with ventral striatal compartments of prefrontal corticostriatal projections in the rat.

The anterograde tracer Phaseolus vulgaris-leucoagglutinin was used to examine the topographical organization of the projections to the striatum arising from the various cytoarchitectonic subdivisions of the prefrontal cortex in the rat. The relationship of the prefrontal cortical fibres with the compartmental organization of the ventral striatum was assessed by combining PHA-L tracing and enkephalin-immunohistochemistry. The prefrontal cortex projects bilaterally with an ipsilateral predominance to the striatum, sparing only the lateral part of the caudate-putamen complex. Each of the cytoarchitectonic subfields of the prefrontal cortex has a longitudinally oriented striatal terminal field that overlaps slightly with those of adjacent prefrontal areas. The projections of the medial subdivision of the prefrontal cortex distribute to rostral and medial parts of the striatum, whereas the lateral prefrontal subdivision projects to more caudal and lateral striatal areas. The terminal fields of the orbital prefrontal areas involve midventral and ventromedial parts of the caudate-putamen complex. The projection of the ventral orbital area overlaps with that of the prelimbic area in the ventromedial part of the caudate-putamen. In the "shell" region of the nucleus accumbens, fibres arising from the prelimbic area concentrate in areas of high cell density that are weakly enkephalin-immunoreactive, whereas fibres from the infralimbic area avoid such areas. Rostrolaterally in the "core" region of the nucleus accumbens, fibres from deep layer V and layer VI of the dorsal part of the prelimbic area avoid the enkephalin-positive areas surrounding the anterior commissure and distribute in an inhomogeneous way over the intervening moderately enkephalin-immunoreactive compartment. The other prefrontal afferents show only a preference for, but are not restricted to, the latter compartment. In the border region between the nucleus accumbens and the ventromedial part of the caudate-putamen complex, patches of strong enkephalin immunoreactivity receive prefrontal cortical input from deep layer V and layer VI, whereas fibres from more superficial cortical layers project to the surrounding matrix. Individual cytoarchitectonic subfields of the prefrontal cortex thus have circumscribed terminal domains in the striatum. In combination with data on the organization of the midline and intralaminar thalamostriatal and thalamoprefrontal projections, the present results establish that the projections of the prefrontal cortical subfields converge in the striatum with those of their midline and intralaminar afferent nuclei. The present findings further demonstrate that the relationship of the prefrontal corticostriatal fibres with the neurochemical compartments of the ventral striatum can be influenced by both the areal and the laminar origin of the cortical afferents, depending on the particular ventral striatal region under consideration.     

Subdivisions and neuron types of the nucleus of the solitary tract that project to the parabrachial nucleus in the hamster

The solitary nuclear complex (NST) consists of a number of subdivisions that differ in their cytoarchitectonic features as well as in the amounts of inputs they receive from lingual afferent axons. In this study horseradish peroxidase (HRP) was injected into the parabrachial nucleus (PBN) of the hamster to determine which of these subdivisions contain cells that project to the pons. In the rostral, gustatory division of the NST, the rostral central subdivision contains the greatest number of labelled pontine-projection neurons. The rostral lateral subdivision contains moderate numbers of labelled cells; progressively fewer labelled cells are in the ventral, medial, and dorsal subdivisions. In the caudal, general viscerosensory division of the NST, the caudal central subdivision contains the majority of labelled cells, although fewer than its rostral counterpart. Progressively fewer cells are labelled in the medial, laminar, ventrolateral, and lateral subdivisions; none in the dorsolateral subdivision. Small horseradish peroxidase injections into the pons revealed that cells of the rostral central and rostral lateral subdivisions of the NST project to the medial subdivision of the PBN, predominantly to caudal and ventral parts of the subdivision. Cells of the caudal central and medial subdivisions of the NST project to the central lateral subdivision of the PBN, predominantly to intermediate and rostral-dorsal parts of the subdivision. Outside the NST, cells in the spinal trigeminal nucleus and parvicellular reticular formation were also labelled after PBN injections. Within the rostral central and rostral lateral (gustatory) subdivisions of the NST at least two types of neurons, distinguished on the basis of dendritic and cell body morphology, were labelled after HRP injections that included the medial PBN. Elongate cells have ovoid-fusiform somata and dendrites oriented in the mediolateral plane parallel to primary afferent axons entering from the solitary tract. Stellate cells have triangular or polygonal cell bodies and three to five dendrites oriented in all directions, although one or two often extend mediolaterally. These results indicate that cytoarchitectonic subdivisions of the NST are distinguished by their efferent ascending connections. For each subdivision within the rostral, gustatory NST there is a correlation between the density of lingual inputs it receives and the density of pontine-projection neurons it contains. Within the rostral central subdivision, which contains the densest lingual inputs and the largest collection of PBN-projection neurons, cell types previously identified in studies with the Golgi method were found to send their axons to the PBN. The presence of two types of pontine-projection cells in the rostral central subdivision provides a structural basis for parallel information processing in the ascending gustatory system. Projections to the PBN from regions outside the NST provide opportunities for convergence, at the level of the pons, between inputs arising from gustatory/general viscerosensory subdivisions of the NST and from trigeminal sensory nuclei and the reticular formation.     

Parahippocampal and retrosplenial connections of rat posterior parietal cortex

The posterior parietal cortex has been implicated in spatial functions, including navigation. The hippocampal and parahippocampal region and the retrosplenial cortex are crucially involved in navigational processes and connections between the parahippocampal/retrosplenial domain and the posterior parietal cortex have been described. However, an integrated account of the organization of these connections is lacking. Here, we investigated parahippocampal connections of each posterior parietal subdivision and the neighboring secondary visual cortex using conventional retrograde and anterograde tracers as well as transsynaptic retrograde tracing with a modified rabies virus. The results show that posterior parietal as well as secondary visual cortex entertain overall sparse connections with the parahippocampal region but not with the hippocampal formation. The medial and lateral dorsal subdivisions of posterior parietal cortex receive sparse input from deep layers of all parahippocampal areas. Conversely, all posterior parietal subdivisions project moderately to dorsal presubiculum, whereas rostral perirhinal cortex, postrhinal cortex, caudal entorhinal cortex and parasubiculum all receive sparse posterior parietal input. This indicated that the presubiculum might be a major liaison between parietal and parahippocampal domains. In view of the close association of the presubiculum with the retrosplenial cortex, we included the latter in our analysis. Our data indicate that posterior parietal cortex is moderately connected with the retrosplenial cortex, particularly with rostral area 30. The relative sparseness of the connectivity with the parahippocampal and retrosplenial domains suggests that posterior parietal cortex is only a modest actor in forming spatial representations underlying navigation and spatial memory in parahippocampal and retrosplenial cortex. © 2017 Wiley Periodicals, Inc.     

Topographic organization of the cerebellar nucleocortical projection in the albino rat: an autoradiographic orthograde study

The topography of the cerebellar nucleocortical projection was investigated in the albino rat by experiments employing an autoradiographic orthograde tracing method. The present results indicate that neurons in the deep cerebellar nuclei project to the granule cell layer of cerebellar cortex as mossy fiber terminals in an orderly way. Thus, the medial cerebellar nucleus projects mainly to the bilateral vermis with ipsilateral dominance. The interpositus and lateral cerebellar nuclei project mainly to the intermediate and lateral zones of the anterior and posterior lobes of the cortex, respectively. The paraflocculus and flocculus receive the nucleocortical projection from the caudal and ventral parts of the interpositus nuclei and the dentate nucleus. A mediolateral topography within each subdivision of the cerebellar nuclear complex was observed; the medial and lateral parts of the subdivision project to the more medial and lateral portions of the primary cortical targets of the subdivision, respectively.     

Retrograde study of projections from the tuberomammillary nucleus to the dorsal raphe and the locus coeruleus in the rat

In the first series of experiments, a retrograde tracer, WGA-apo-HRP-gold (WG), was injected into the dorsal raphe (DR) or the locus coeruleus (LC) and adenosine deaminase immunostaining was subsequently performed for the tuberomammillary nucleus (TMN) in order to investigate projections from the TMN to the two brainstem monoaminergic nuclei. Following rostral DR injections, the majority of retrogradely labeled cells were located in the dorsomedial and ventrolateral subdivisions of the TMN. At middle DR levels, midline injections resulted in labeling mainly in the ventrolateral subdivision, whereas lateral wing injections produced labeling mostly in ventral and caudal TMN subdivisions. When injections were made in the caudal DR, only a few cells were observed along the rostro-caudal extent of the TMN. On the other hand, following rostral LC injections, labeled neurons were observed mainly in ventrolateral and ventral subdivisions of TMN. For principal LC injections, labeled cells were observed mostly in ventrolateral, ventral, and caudal TMN subdivisions, whereas for injections at caudal pole of LC, only a few cells were located along the rostro-caudal extent of the TMN. In the second series of experiments, an iontophoretic injection of fluorogold (FG) into the DR was paired with a pressure injection of WG into the LC to investigate the collateral distribution of TMN axonal fibers to DR and LC. Double-labeled cells were observed in ventrolateral, ventral, and caudal TMN subdivisions. The present study indicated that there exists a robust projection from the TMN to the DR or the LC and that some TMN neurons have axon collaterals projecting to both DR and LC. The TMN neurons with such axon collaterals might provide simultaneous, possibly more efficient, way of controlling the brainstem monoaminergic nuclei, thus influencing various sleep and arousal states of the animal.     

Hodological characterization of the septum in anuran amphibians: I. Afferent connections

On the basis of Nissl-stained sections, we subdivided the septum of the gray treefrog Hyla versicolor in the lateral, central, and medial septal complex. The afferent projections of the different septal nuclei were studied by combined retrograde and anterograde tracing with biotin ethylendiamine (Neurobiotin). The central and medial septal complex receives direct input from regions of the olfactory bulb and from all other limbic structures of the telencephalon (e.g., amygdalar regions, nucleus accumbens), whereas projections to the lateral septal complex are absent or less extensive. The medial pallium projects to all septal nuclei. In the diencephalon, the anterior thalamic nucleus provides the main ascending input to all subnuclei of the anuran septum, which can be interpreted as a limbic/associative pathway. The ventromedial thalamic nucleus projects to the medial and lateral septal complex and may thereby transmit multisensory information to the limbic system. Anterior preoptic nucleus, suprachiasmatic nucleus, and hypothalamic nuclei innervate the central and lateral septal complex. Only the nuclei of the central septal complex receive input from the brainstem. Noteworthy is the relatively strong projection from the nucleus raphe to the central septal complex, but not to the other septal nuclei.     

Afferent connections of the medial frontal cortex of the rat. II. Cortical and subcortical afferents

In order to compare the frontal cortex of rat and macaque monkey, cortical and subcortical afferents to subdivisions of the medial frontal cortex (MFC) in the rat were analyzed with fluorescent retrograde tracers. In addition to afferent inputs common to the whole MFC, each subdivision of the MFC has a specific pattern of afferent connections. The dorsally situated precentral medial area (PrCm) was the only area to receive inputs from the somatosensory cortex. The specific pattern of afferents common to the ventrally situated prelimbic (PL) and infralimbic (IL) areas included projections from the agranular insular cortex, the entorhinal and piriform cortices, the CA1–CA2 fields of the hippocampus, the subiculum, the endopiriform nucleus, the amygdalopiriform transition, the amygdalohippocampal area, the lateral tegmentum, and the parabrachial nucleus. In all these structures, the number of retrogradely labeled cells was larger when the injection site was located in area IL. The dorsal part of the anterior cingulate area (ACd) seemed to be connectionally intermediate between the adjacent areas PrCm and PL; it receives neither the somatosensory inputs characteristic of area PrCm nor the afferents characteristic of areas PL and IL, with the exception of the afferents from the caudal part of the retrosplenial cortex. A comparison of the pattern of afferent and efferent connections of the rat MFC with the pattern of macaque prefrontal cortex suggests that PrCm and ACd areas share some properties with the macaque premotor cortex, whereas PL and IL areas may have characteristics in common with the cingulate or with medial areas 24, 25, and 32 and with orbital areas 12, 13, and 14 of macaques. © 1995 Wiley-Liss, Inc.     

Insular and gustatory inputs to the caudal ventral striatum in primates

The ventral striatum mediates goal-directed behaviors based, in part, on inputs from the amygdala. However, striatal areas caudal to the ventral striatum also receive inputs from the amygdala. In primates, the amygdala projects to the central ventral putamen, lateral amygdalostriatal area, and caudal ventral putamen, suggesting that these regions are also "limbic-related." The anterior insula, which integrates sensory and amygdaloid inputs, projects to the classic ventral striatum. We used retrograde and anterograde tract tracing techniques to determine the extent to which specific subdivisions of the insula influence the caudal ventral striatum in the primate. The anterior (agranular and rostral dysgranular) insula has significant inputs to caudal ventral striatal regions that receive projections from the amygdala. In contrast, the posterior (granular) insula has sparse projections. Within the agranular insula, the posteromedial agranular (Iapm), lateral agranular (Ial), and posterolateral agranular (Iapl) subdivisions have the strongest inputs. These subdivisions mediate olfactory, gustatory, and visceral information processing (Carmichael and Price JL [1996b] J. Comp. Neurol. 363:642-640). In contrast, the intermediate agranular subdivision (Iai) is relatively devoid of visceral/gustatory inputs and has few inputs. In summary, caudal ventral striatal areas that receive amygdaloid inputs also receive significant innervation by agranular and dysgranular insula subdivisions that are themselves connected with the amygdala. Within this projection, the Ial, Iapm, and Iapl make the strongest contribution, suggesting that highly processed visceral/autonomic information, taste, and olfaction influence behavioral responses mediated by the caudal ventral striatum.     

Thalamotelencephalic organization in birds

Investigation of thalamo-telencephalic connections reveals correspondences between the avian and mammalian thalamic subdivisions (which may or may not mean true homologies). Based mainly on hodological comparisons, the avian thalamus possesses the principal anatomical and functional subdivisions characteristic for mammals. The current review is focused on a comparative analysis of intralaminar, midline and mediodorsal nuclei. There is evidence for matching subdivisions in the case of midline thalamic and mediodorsal nuclei within the avian dorsal thalamic zone, whereas such correspondence is evident, if less complete, in the case of the intralaminar nuclei. Thalamic connections are also relevant to the debated issue of the avian 'prefrontal' cortex. From the current study it is suggested that the prefrontal analogue regions of the bird may spread across the rostrocaudal extent of telencephalon, the rostral nidopallial/mesopallial region (formerly known as medial neostriatum/hyperstriatum) being one subdivision, receiving direct input from the paraventricular thalamic nucleus homologue of midline thalamic region (the medial juxtaventricular region of the nucleus dorsomedialis posterior). Hodological evidence from the current study and other reports argues for the possibility that the area corticoidea dorsolateralis might be hodologically comparable to the cingulate cortex, receiving input from a mediodorsal thalamic-relevant subdivision (lateral subdivision of nucleus dorsomedialis anterior, and medial aspect of nucleus dorsolateralis pars medialis), which also projects on the caudal nidopallium close to (but not coextensive with) the nidopallium caudolaterale, another potential analogue of avian prefrontal cortex. The rostral dorsolateral aspect of nucleus dorsomedialis anterior thalami and the dorsal aspect of nucleus dorsolateralis pars medialis are partially comparable to the mammalian intralaminar nuclei, sharing connections to non-limbic 'corticoid' areas (the Wulst), and the reticular thalamic nuclei.     

Ventral nucleus of the lateral lemniscus in guinea pigs: Cytoarchitecture and inputs from the cochlear nucleus

Cytoarchitectonic criteria were used to distinguish three subdivisions of the ventral nucleus of the lateral lemniscus in guinea pigs. Axonal tracing techniques were used to examine the projections from the cochlear nucleus to each subdivision. Based on the cell types they contain and their patterns of input, we distinguished ventral, dorsal, and anterior subdivisions of the ventral nucleus of the lateral lemniscus. All three subdivisions receive bilateral inputs from the cochlear nucleus, with contralateral inputs greatly outnumbering ipsilateral inputs. However, the relative density of the inputs varies: the ventral subdivision receives the densest projection, whereas the anterior subdivision receives the sparsest projection. Further differences are apparent in the morphology of the afferent axons. Following an injection of Phaseolus vulgaris-leucoagglutinin into the ventral cochlear nucleus, most of the axons on the contralateral side and all of the axons on the ipsilateral side are thin. Thick axons are present only in the ventral subdivision contralateral to the injection site. The evidence from both anterograde and retrograde tracing studies suggests that the thick axons originate from octopus cells, whereas the thin axons arise from multipolar cells and spherical bushy cells. The differences in constituent cell types and in patterns of inputs suggest that each of the three subdivisions of the ventral nucleus of the lateral lemniscus makes a distinct contribution to the analysis of acoustic signals. J. Comp. Neurol. 379:363–385, 1997. © 1997 Wiley-Liss, Inc.     

Amygdaloid inputs define a caudal component of the ventral striatum in primates

The ventral striatum mediates goal-directed behavior through limbic afferents. One well-established afferent to the ventral striatum is the amygdaloid complex, which projects throughout the shell and core of the nucleus accumbens, the rostral ventromedial caudate nucleus, and rostral ventromedial putamen. However, striatal regions caudal to the anterior commissure also receive inputs from the amygdala. These caudal areas contain histochemical and cytoarchitectural features that resemble the shell and core, based on our recent studies. Specifically, there is a calcium binding protein (CaBP)-poor region in the lateral amygdalostriatal area that resembles the "shell." To examine the idea that the caudal ventral striatum is part of the "classic" ventral striatum, we placed small injections of retrograde tracers throughout the caudal ventral striatum/amygdalostriatal area and charted the distribution of specific amygdaloid inputs. Amygdaloid inputs to the CaBP-poor zone in the lateral amygdalostriatal area arise from the basal nucleus, the magnocellular subdivision of the accessory basal nucleus, the periamygdaloid cortex, and the medial subdivision of the central nucleus, resembling that of the shell of the ventral striatum found in our previous studies. There are also amygdaloid inputs to CaBP-positive areas outside the shell, which originate mainly in the basal nucleus. Taken together, the "limbic-related" striatum forms a continuum from the rostral ventral striatum through the caudal ventral striatum/lateral amygdalostriatal area based on histochemical and cellular similarities, as well as inputs from the amygdala.     

Patterns of afferent input to the caudal and rostral areas of the dorsal premotor cortex (6DC and 6DR) in the marmoset monkey

Corticocortical projections to the caudal and rostral areas of dorsal premotor cortex (6DC and 6DR, also known as F2 and F7) were studied in the marmoset monkey. Both areas received their main thalamic inputs from the ventral anterior and ventral lateral complexes, and received dense projections from the medial premotor cortex. However, there were marked differences in their connections with other cortical areas. While 6DR received consistent inputs from prefrontal cortex, area 6DC received few such connections. Conversely, 6DC, but not 6DR, received major projections from the primary motor and somatosensory areas. Projections from the anterior cingulate cortex preferentially targeted 6DC, while the posterior cingulate and adjacent medial wall areas preferentially targeted 6DR. Projections from the medial parietal area PE to 6DC were particularly dense, while intraparietal areas (especially the putative homolog of LIP) were more strongly labeled after 6DR injections. Finally, 6DC and 6DR were distinct in terms of inputs from the ventral parietal cortex: projections to 6DR originated preferentially from caudal areas (PG and OPt), while 6DC received input primarily from rostral areas (PF and PFG). Differences in connections suggest that area 6DR includes rostral and caudal subdivisions, with the former also involved in oculomotor control. These results suggest that area 6DC is more directly involved in the preparation and execution of motor acts, while area 6DR integrates sensory and internally driven inputs for the planning of goal‐directed actions. They also provide strong evidence of a homologous organization of the dorsal premotor cortex in New and Old World monkeys. J. Comp. Neurol. 522:3683–3716, 2014. © 2014 Wiley Periodicals, Inc.     

Afferent projections to the mammillary complex of the rat, with special reference to those from surrounding hypothalamic regions.

To better understand the functional organization of the mammillary nuclei, we investigated the afferents to this nuclear complex in the rat with iontophoretically injected wheat germ agglutinin conjugated to horseradish peroxidase. Particular attention was paid to tracing local hypothalamic afferents to these nuclei. Injections into the medial mammillary nucleus (MMN) revealed strong projections from the subicular region, and weaker projections from the prefrontal cortex, medial septum, and the nucleus of the diagonal band of Broca. Other descending subcortical projections to the MMN arise from the anterior and the lateral hypothalamic area, the medial preoptic area, and the bed nucleus of the stria terminalis. Ascending afferents to the MMN were found to originate in the raphe and various tegmental nuclei. Following all injections into the MMN, labelled neurons were found in nuclei surrounding the mammillary body. The lateral and posterior subdivisions of the tuberomammillary nucleus projected mainly to the pars medianus and pars medialis of the MMN. The dorsal and ventral premammillary nuclei projected to the pars lateralis of the MMN. The supramammillary nucleus at rostral level had a small projection to the pars medialis and lateralis of the MMN. However, the most obvious projection from this nucleus was to the pars posterior of the MMN, chiefly from the lateral part of the caudal supramammillary nucleus. Injections into the lateral mammillary nucleus revealed inputs from the presubiculum, parasubiculum, septal region, dorsal tegmental nucleus, dorsal raphe nucleus, and periaqueductal gray. In addition, the lateral mammillary nucleus was found to receive a moderate projection from the medial part of the supramammillary nucleus and stronger projections from the lateral part of the caudal supramammillary nucleus. A very light projection was also seen from the lateral and posterior subdivisions of the tuberomammillary nucleus. These findings add to our knowledge of the extensive and complex connectivity of the mammillary nuclei. In particular, the local connections we have demonstrated with the supramammillary and tuberomammillary nuclei indicate the existence of significant local circuits as well as circuits involving more distant brain regions such as the septal nuclei, subiculum, prefrontal cortex, and brain stem tegmentum.     

Some observations on cortical inputs to the macaque monkey amygdala: an anterograde tracing study

We have previously described the origins of neocortical inputs to the lateral nucleus of the macaque monkey amygdala based on retrograde tracing studies. Here we report results from studies that have attempted to confirm the projections from several candidate afferent regions using (3)H-amino acid autoradiography as an anterograde tracer. We have charted, based on the results of 33 separate injections, the topographic distribution of cortical projections throughout the amygdala. Areas TE and TEO of the inferotemporal cortex, portions of the superior temporal gyrus, and the granular region of the insula project primarily to the lateral nucleus, with little or no innervation of other amygdaloid nuclei. In contrast, orbitofrontal, medial prefrontal, and anterior cingulate regions project primarily to the basal and accessory basal nuclei and provide little innervation to the lateral nucleus. The orbitofrontal and medial prefrontal cortices, but not the anterior cingulate cortex, project to medially situated amygdaloid areas such as the cortical and medial nuclei and to the periamygdaloid cortex. The agranular and dysgranular insula, the parainsula, and rostral portions of the superior temporal gyrus project both to the lateral, basal, and accessory basal nuclei and to the medially situated nuclei. Projections to the central nucleus are particularly prominent from these regions. These data are discussed in relation to the hierarchical processing of sensory information that occurs within the amygdaloid complex.     

Organization of neural inputs to the suprachiasmatic nucleus in the rat

The circadian timing of the suprachiasmatic nucleus (SCN) is modulated by its neural inputs. In the present study, we examine the organization of the neural inputs to the rat SCN using both retrograde and anterograde tracing methods. After Fluoro-Gold injections into the SCN, retrogradely labeled neurons are present in a number of brain areas, including the infralimbic cortex, the lateral septum, the medial preoptic area, the subfornical organ, the paraventricular thalamus, the subparaventricular zone, the ventromedial hypothalamic nucleus, the posterior hypothalamic area, the intergeniculate leaflet, the olivary pretectal nucleus, the ventral subiculum, and the median raphe nuclei. In the anterograde tracing experiments, we observe three patterns of afferent termination within the SCN that correspond to the photic/raphe, limbic/hypothalamic, and thalamic inputs. The median raphe projection to the SCN terminates densely within the ventral subdivision and sparsely within the dorsal subdivision. Similarly, areas that receive photic input, such as the retina, the intergeniculate leaflet, and the pretectal area, densely innervate the ventral SCN but provide only minor innervation of the dorsal SCN. A complementary pattern of axonal labeling, with labeled fibers concentrated in the dorsal SCN, is observed after anterograde tracer injections into the hypothalamus and into limbic areas, such as the ventral subiculum and infralimbic cortex. A third, less common pattern of labeling, exemplified by the paraventricular thalamic afferents, consists of diffuse axonal labeling throughout the SCN. Our results show that the SCN afferent connections are topographically organized. These hodological differences may reflect a functional heterogeneity within the SCN. J. Comp. Neurol. 389:508–534, 1997. © 1997 Wiley-Liss, Inc.     

The organization of projections from the cortex, amygdala, and hypothalamus to the nucleus of the solitary tract in rat

Direct projections from the forebrain to the nucleus of the solitary tract (NTS) and dorsal motor nucleus of the vagus in the rat medulla were mapped in detail using both retrograde axonal transport of the fluorescent tracer True Blue and anterograde axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). In the retrograde tracing studies, cell groups in the medial prefrontal cortex, lateral prefrontal cortex (primarily ventral and posterior agranular insular cortex), bed nucleus of the stria terminalis, central nucleus of the amygdala, paraventricular, arcuate, and posterolateral areas of the hypothalamus were shown to project to the NTS and in some cases also to the dorsal motor nucleus of the vagus. The prefrontal cortical areas projecting to the NTS apparently overlap to a large degree with those cortical areas receiving mediodorsal thalamic and dopaminergic input. The retrogradely labeled cortical cells were situated in deep layers of the rat prefrontal cortex. The anterograde tracing studies revealed a prominent topography in the mediolateral termination pattern of forebrain projections to the rostral part of the NTS and to the dorsal pons. The projections to the NTS were generally bilateral, except for projections from the central nucleus of the amygdala and bed nucleus of the stria terminalis which were predominantly ipsilateral. The prefrontal cortical projections to the NTS travel through the cerebral peduncle and pyramidal tract and terminate throughout the rostrocaudal extent of the NTS. Specifically, the prefrontal cortex innervates dorsal portions of the NTS (lateral part of the dorsal division of the medial solitary nucleus, dorsal part of the lateral solitary nucleus and the caudal midline region of the commissural nucleus), areas which receive relatively sparse subcortical projections. These dorsal portions of the NTS receive major primary afferent projections from the vagal and glossopharyngeal nerves. In contrast, the subcortical projections, which travel through the midbrain and pontine tegmentum, terminate most heavily in the ventral portions of the NTS, i.e., the area immediately dorsal and lateral to the dorsal motor nucleus of the vagus. Only the paraventricular hypothalamic nucleus has substantial terminals throughout the dorsal motor nucleus of the vagus. Hypothalamic cell groups innervate the area postrema and, along with the prefrontal cortex, innervate the zone subjacent to the area postrema.(ABSTRACT TRUNCATED AT 400 WORDS)     

Forebrain projections to the rostral nucleus of the solitary tract in the hamster

The rostral nucleus of the solitary tract (NST) is the first central site of taste information processing. Specific anatomical subdivisions of the NST receive taste afferent input and contain interneurons and projection neurons that engage ascending or premotor taste pathways. The forebrain projects to the NST and can influence taste responses, but the anatomical relationship between forebrain inputs and the subdivisions of the NST and their cellular elements is not understood. To evaluate this, in this study, we used cholera toxin B (CTb) as a retrograde and anterograde marker. CTb was injected into the rostral NST to label, by retrograde transport, the sources of forebrain inputs. Cells were labeled bilaterally in the lateral and paraventricular hypothalamic nuclei, bed nucleus of the stria terminalis, central nuclei of the amygdala, and the agranular and dysgranular divisions of insular cortex. Within the medulla, labeled cells were located in the parvicellular reticular formation and spinal trigeminal nuclei. In addition, labeled cells and anterograde axonal labeling were present in the rostral NST contralateral to the injections. Injections of CTb centered in the dysgranular insular cortex, the site of most forebrain-NST cells, labeled axon endings confined to the rostral NST. These endings were concentrated in the rostral central and ventral subdivisions. Corticofugal endings in the rostral central subdivision are positioned to influence microcircuits that include taste afferent synapses, presumed inhibitory interneurons, and neurons that project to the parabrachial nucleus. The many corticofugal endings in the ventral subdivision synapse among premotor neurons that ultimately influence salivatory and oromotor outflow. Intramedullary CTb labeling after NST injection indicates that the rostral central subdivision also receives projections from the contralateral rostral NST.     

A survey of oral cavity afferents to the rat nucleus tractus solitarii

Visualization of myelinated fiber arrangements, cytoarchitecture, and projection fields of afferent fibers in tandem revealed input target selectivity in identified subdivisions of the nucleus tractus solitarii (NTS). The central fibers of the chorda tympani (CT), greater superficial petrosal nerve (GSP), and glossopharyngeal nerve (IX), three nerves that innervate taste buds in the oral cavity, prominently occupy the gustatory-sensitive rostrocentral subdivision. In addition, CT and IX innervate and overlap in the rostrolateral subdivision, which is primarily targeted by the lingual branch of the trigeminal nerve (LV). In the rostrocentral subdivision, compared with the CT terminal field, GSP appeared more rostral and medial, and IX was more dorsal and caudal. Whereas IX and LV filled the rostrolateral subdivision diffusely, CT projected only to the dorsal and medial portions. The intermediate lateral subdivision received input from IX and LV but not CT or GSP. In the caudal NTS, the ventrolateral subdivision received notable innervation from CT, GSP, and LV, but not IX. No caudal subnuclei medial to the solitary tract contained labeled afferent fibers. The data indicate selectivity of fiber populations within each nerve for functionally distinct subdivisions of the NTS, highlighting the possibility of equally distinct functions for CT in the rostrolateral NTS, and CT and GSP in the caudal NTS. Further, this provides a useful anatomical template to study the role of oral cavity afferents in the taste-responsive subdivision of the NTS as well as in subdivisions that regulate ingestion and other oromotor behaviors.