Orbitomedial prefrontal cortical projections to distinct longitudinal columns of the periaqueductal gray in the rat

We utilised retrograde and anterograde tracing procedures to study the origin and termination of prefrontal cortical (PFC) projections to the periaqueductal gray (PAG) in the rat. A previous study, in the primate, had demonstrated that distinct subgroups of PFC areas project to specific PAG columns. Retrograde tracing experiments revealed that projections to dorsolateral (dlPAG) and ventrolateral (vlPAG) periaqueductal gray columns arose from medial PFC, specifically prelimbic, infralimbic, and anterior cingulate cortices. Injections made in the vlPAG also labeled cells in medial, ventral, and dorsolateral orbital cortex and dorsal and posterior agranular insular cortex. Other orbital and insular regions, including lateral and ventrolateral orbital, ventral agranular insular, and dysgranular and granular insular cortex did not give rise to appreciable projections to the PAG. Anterograde tracing experiments revealed that the projections to different PAG columns arose from specific PFC areas. Projections from the caudodorsal medial PFC (caudal prelimbic and anterior cingulate cortices) terminated predominantly in dlPAG, whereas projections from the rostroventral medial PFC (rostral prelimbic cortex) innervated predominantly the vlPAG. As well, consistent with the retrograde data, projections arising from select orbital and agranular insular cortical areas terminated selectively in the vlPAG. The results indicate: (1) that rat orbital and medial PFC possesses an organisation broadly similar to that of the primate; and (2) that subdivisions within the rat orbital and medial PFC can be recognised on the basis of projections to distinct PAG columns.     

Topographical organization of the efferent projections of the medial prefrontal cortex in the rat: an anterograde tract-tracing study with Phaseolus vulgaris leucoagglutinin

The purpose of the present investigation was to examine the topographical organization of efferent projections from the cytoarchitectonic divisions of the mPFC (the medial precentral, dorsal anterior cingulate and prelimbic cortices). We also sought to determine whether the efferents from different regions within the prelimbic division were organized topographically. Anterograde transport of Phaseolus vulgaris leucoagglutinin was used to examine the efferent projections from restricted injection sites within the mPFC. Major targets of the prelimbic area were found to include prefrontal, cingulate, and perirhinal cortical structures, the dorsomedial and ventral striatum, basal forebrain nuclei, basolateral amygdala, lateral hypothalamus, mediodorsal, midline and intralaminar thalamic nuclei, periaqueductal gray region, ventral midbrain tegmentum, laterodorsal tegmental nucleus, and raphe nuclei. Previously unreported projections of the prelimbic region were also observed, including efferents to the anterior olfactory nucleus, the piriform cortex, and the pedunculopontine tegmental-cuneiform region. A topographical organization governed the efferent projections from the prelimbic area, such that the position of terminal fields within target structures was determined by the rostrocaudal, dorsoventral, and mediolateral placement of the injection sites. Efferent projections from the medial precentral and dorsal anterior cingulate divisions (dorsomedial PFC) were organized in a similar topographical fashion and produced a pattern of anterograde labeling different from that seen with prelimbic injection sites. Target structures innervated primarily by the dorsomedial PFC included certain neocortical fields (the motor, somatosensory, and visual cortices), the dorsolateral striatum, superior colliculus, deep mesencephalic nucleus, and the pontine and medullary reticular formation. Previously unreported projections to the paraoculomotor central gray area and the mesencephalic trigeminal nucleus were observed following dorsomedial PFC injections. These results indicate that the efferent projections of the mPFC are topographically organized within and across the cytoarchitectonic divisions of the medial wall cortex. The significance of topographically organized and restricted projections of the rat mPFC is discussed in light of behavioral and physiological studies indicating functional heterogeneity of this region.     

Topographical organization of the cortical afferent connections of the prefrontal cortex in the cat

The topographical distribution of the cortical afferent connections of the prefrontal cortex (PFC) in adult cats was studied by using the retrograde axonal transport of horseradish peroxidase technique. Small single injections of the enzyme were made in different locations of the PFC, and the areal location and density of the subsequent neuronal labeling in neocortex and allocortex were evaluated in each case. The comparison of the results obtained in the various cases revealed that four prefrontal sectors (rostral, dorsolateral, ventral, and dorsomedial) can be distinguished, each exhibiting a particular pattern of cortical afferents. All PFC sectors receive projections from the ipsilateral insular (agranular and granular subdivisions) and limbic (infralimbic, prelimbic, anterior limbic, cingular, and retrosplenial areas) cortices. These cortices provide the most abundant cortical projections to the PFC, and their various subdivisions have different preferential targets within the PFC. The premotor cortex and the following neocortical sensory association areas project differentially upon the various ipsilateral PFC sectors: the portion of the somatosensory area SIV in the upper bank of the anterior ectosylvian sulcus, the visual area in the lower bank of the same sulcus, the auditory area AII, the temporal area, the perirhinal cortex, the posterior suprasylvian area, area 20, the posterior ectosylvian area, the suprasylvian fringe, the lateral suprasylvian area (anterolateral and posterolateral subdivisions), area 5, and area 7. The olfactory peduncle, the prepiriform cortex, the cortico-amygdaloid transition area, the entorhinal cortex, the subiculum (ventral, posteroventral, and posterodorsal sectors), the caudomedial band of the hippocampal formation and the postsubiculum are the allocortical sources of afferents to the PFC. The dorsolateral PFC sector is the target of the largest insular, limbic, and neocortical sensory association projections. The dorsomedial and rostral sectors receive notably less abundant cortical afferents than the dorsolateral sector. Those to the dorsomedial sector arise from the same areas that project to the dorsolateral sector and are more abundant to the dorsal part, where the medial frontal eye field cortex is located. The rostral sector receives projections principally from all other PFC sectors, and from the limbic and insular cortices. The projections from the allocortex reach preferentially the ventral PFC sector. Intraprefrontal connections are most abundant within each PFC sector. Commissural interprefrontal connections are largest from the site homotopic to the HRP injection.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cortically projecting cells in the periaqueductal gray matter of the rat. A retrograde fluorescent tracer study

The topographical organization of the afferent input from the periaqueductal gray matter (PAG) to the cerebral cortex has been assessed in rats by retrograde transport of the fluorescent tracers Fast blue (FB) and Diamidino yellow (DY). The olfactory, medial frontal (infralimbic, prelimbic and anterior cingulate cortices), lateral frontal (motor), parietal, temporal, occipital and insular cortices were explored by placing two fluorescent tracers into two different cortical regions. The PAG contained the largest number of labeled neurons in medial frontal cortex injections, followed by olfactory and lateral frontal cortices. Fewer retrogradely labeled cells were seen after injections in parietal, temporal occipital and insular cortices. All labeled cells were exclusively located in the medial and lateroventral divisions of the PAG (PAGm and PAGlv). The longitudinal extent of the labeling in PAGm was more extensive than in PAGlv. The labeled neurons in the medial frontal cortex group extended through most of the PAG, while in the remaining groups it was restricted to the caudal one-third of the PAG. Neurons with projections to two different cortical regions were only a small fraction of the total population of labeled cells. Our data indicate that the medial frontal cortex is the most important recipient of a direct PAG input, followed by the lateral frontal cortex. Parietal, temporal, occipital and insular cortices receive only a minor projection. It is concluded that the PAG sends direct projections over the majority of the cortical mantle. Therefore, the possibility arises that the cerebral cortex receives a direct influence from the brainstem without a thalamic relay.     

The rat medial frontal cortex projects directly to autonomic regions of the brainstem

Pressure injections of the anterograde tracer wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) into the infralimbic (IL) and prelimbic (PL) regions of the medial frontal cortex of the rat produced anterograde, terminal-like labeling in the lateral dorsal tegmental nucleus (LDTg) of the dorsal pons and the ventral, ventrolateral, intermediate, medial and commissural subnuclei of the nucleus of the solitary nucleus (NTS) in the dorsomedial medulla. Injections involving IL resulted in heavier labeling than the labeling seen after PL injections only. The LDTg has been described as the pontine micturition center, involved in the micturition reflex. The possible role that the projections to the LDTg may play in fluid homeostasis is discussed. The labeled NTS subnuclei receive visceral afferent inputs from the heart, baroreceptors, lungs and gut. The direct cortical projections to these areas may be involved in mediating the bradycardia, depressor responses, and changes in respiratory and gastric activity which are seen after electrical stimulation of the rat medial frontal cortex. The present data support the concept that the infralimbic and prelimbic cortices function as a "visceral motor" cortex, involved in control of a variety of autonomic functions.     

Auditory belt and parabelt projections to the prefrontal cortex in the Rhesus monkey

Recent anatomical and electrophysiological studies have expanded our knowledge of the auditory cortical system in primates and have described its organization as a series of concentric circles with a central or primary auditory core, surrounded by a lateral and medial belt of secondary auditory cortex with a tertiary parabelt cortex just lateral to this belt. Because recent studies have shown that rostral and caudal belt and parabelt cortices have distinct patterns of connections and acoustic responsivity, we hypothesized that these divergent auditory regions might have distinct targets in the frontal lobe. We, therefore, placed discrete injections of wheat germ agglutinin-horseradish peroxidase or fluorescent retrograde tracers into the prefrontal cortex of macaque monkeys and analyzed the anterograde and retrograde labeling in the aforementioned auditory areas. Injections that included rostral and orbital prefrontal areas (10, 46 rostral, 12) labeled the rostral belt and parabelt most heavily, whereas injections including the caudal principal sulcus (area 46), periarcuate cortex (area 8a), and ventrolateral prefrontal cortex (area12vl) labeled the caudal belt and parabelt. Projections originating in the parabelt cortex were denser than those arising from the lateral or medial belt cortices in most cases. In addition, the anterior third of the superior temporal gyrus and the dorsal bank of the superior temporal sulcus were also labeled after prefrontal injections, confirming previous studies. The present topographical results suggest that acoustic information diverges into separate streams that target distinct rostral and caudal domains of the prefrontal cortex, which may serve different acoustic functions. J. Comp. Neurol. 403:141–157, 1999. © 1999 Wiley-Liss, Inc.     

Heterotopic Cortical Afferents to the Medial Prefrontal Cortex in the Rat. A Combined Retrograde and Anterograde Tracer Study

Cortical afferent projections towards the medial prefrontal cortex (mPFC) were investigated with retrograde and anterograde tracer techniques. Heterotopical afferent projections to the medial prefrontal cortex arise in secondary, or higher order, sensory areas, motor areas and paralimbic cortices. On the basis of these projections three subfields can be discriminated within the mPFC. (1) The ventromedial part of mPFC, comprising the pre- and infralimbic areas, receives mainly projections from the perirhinal cortex. (2) The caudal two-thirds of the dorsomedial PFC, comprising frontal area 2 and the dorsal anterior cingulate area, receives projections from the secondary visual areas, the posterior agranular insular area and the retrosplenial areas. (3) The rostral one-third of the dorsomedial PFC is the main recipient of projections from the somatosensory and motor areas and the posterior agranular insular area. The laminar distribution of cells projecting to the mPFC varies considerably in the different cortical areas, just as the laminar distribution of termination of their fibres within the mPFC does. It is concluded that the corticocortical connections corroborate with subcortical connectivity in attributing to the mediodorsal projection cortex of the rat functions which are comparable to those of certain prefrontal, premotor and anterior cingulate areas in the monkey.     

Organization of subcortical pathways for sensory projections to the limbic cortex. II. Afferent projections to the thalamic lateral dorsal nucleus in the rat

Afferent projections to the thalamic lateral dorsal nucleus were examined in the rat by the use of retrograde axonal transport techniques. Small iontophoretic injections of horseradish peroxidase were placed at various locations within the lateral dorsal nucleus, and the location and morphology of cells of origin of afferent projections were identified by retrograde labeling. For all cases examined, subcortical retrogradely labeled neurons were most prominent in the pretectal complex, the intermediate layers of the superior colliculus, and the ventral lateral geniculate nucleus. Labeled cells were also seen in the thalamic reticular nucleus and the zona incerta. Within the cerebral cortex, labeled cells were prominent in the retrosplenial areas (areas 29b, 29c, and 29d) and the presubiculum. Labeled cells were also seen in areas 17 and 18 of occipital cortex. Peroxidase injections in the dorsal lateral part of the lateral dorsal nucleus result in labeled neurons in all of the ipsilateral pretectal nuclei, but especially those that receive direct retinal afferents. Labeled cells were also seen in the ventral lateral geniculate nucleus and the rostral tip of laminae IV-VI of the superior colliculus. In contrast, peroxidase injections in ventral medial portions of the lateral dorsal nucleus result in fewer labeled pretectal cells, and these labeled cells are found exclusively in the pretectal nuclei that do not receive retinal afferents. Other labeled cells following injections in the rostral and medial portions of the lateral dorsal nucleus are seen contralaterally in the medial pretectal region and nucleus of the posterior commissure, and bilaterally in the rostral tips of laminae IV and V of the superior colliculus. Camera lucida drawings of HRP labeled cells reveal that projecting cells in each pretectal nucleus have a characteristic soma size and dendritic branching pattern. These results are discussed with regard to the type of sensory information that may reach the lateral dorsal nucleus and then be relayed on to the medial limbic cortex.     

Prosencephalic afferents to the mediodorsal thalamic nucleus

The afferent projections from the prosencephalon to the mediodorsal thalamic nucleus (MD) were studied in the cat by use of the method of retrograde transport of horseradish peroxidase (HRP). Cortical and subcortical prosencephalic structures project bilaterally to the MD. The cortical afferents originate mainly in the ipsilateral prefrontal cortex. The premotor, prelimbic, anterior limbic, and insular agranular cortical areas are also origins of consistent projections to the MD. The motor cortex, insular granular area, and some other cortical association areas may be the source of cortical connections to the MD. The subcortical projections originate principally in the ipsilateral rostral part of the reticular thalamic nucleus and the rostral lateral hypothalamic area. Other parts of the hypothalamus, the most caudal parts of the thalamic reticular nucleus, the basal prosencephalic structures, the zona incerta, the claustrum, and the entopeduncular and subthalamic nuclei are also sources of projections to the MD. Distinct, but somewhat overlapping areas of the prosencephalon project to the three vertical subdivisions of MD (medial, intermediate, and lateral). The medial band of the MD receives a small number of prosencephalic projections; these arise mainly in the caudal and ventral parts of the prefrontal cortex. Cortical projections also arise in the infralimbic area, while subcortical projections originate in the medial part of the rostral reticular thalamic nucleus and lateral hypothalamic area. The intermediate band of the MD receives the largest number of fibers from the prosencephalon. These arise principally in the intermediate and dorsal part of the lateral and medial surface of the prefrontal cortex, the premotor cortex, and the prelimbic and agranular insular areas. Projections also originate in basal prosencephalic formations (preoptic area, Broca's diagonal band, substantia innominata, and olfactory tubercle), rostral reticular thalamic nucleus, and lateral hypothalamic area. A large number of prosencephalic structures also project to the lateral band of the MD. These are mainly the most dorsal and caudal parts of the lateral and medial surface of the prefrontal cortex, the premotor and motor cortices, and the prelimbic, anterior limbic, and insular areas. Projections arise also in the lateral rostral and caudal parts of the reticular thalamic nucleus, the zona incerta, the lateral and dorsal hypothalamic areas, the claustrum, and the entopeduncular nucleus. These and previous results demonstrate a gradation in the afferent connections to the three subdivisions of the MD. Brain structures related to the olfactory sensory modality and with allocortical formations of the limbic system project principally to the medial band of the MD. The intermediate band of the MD receives subcortical and cortical projections from structures mainly related to the limbic system and cortical regions related to sensory association cortices. The lateral band of the MD receives projections mainly originating in structures related to complex sensory associative processes and to the motor system (especially from brainstem and cortical structures implicated in the regulation of eye movements).     

Cingulate cortex projections to the parahippocampal region and hippocampal formation in the rat

In the present study we aimed to determine the topographical and laminar characteristics of cingulate projections to the parahippocampal region and hippocampal formation in the rat, using the anterograde tracers Phaseolus vulgaris-leucoagglutinin and biotinylated dextranamine. The results show that all areas of the cingulate cortex project extensively to the parahippocampal region but not to the hippocampal formation. Rostral cingulate areas (infralimbic-, prelimbic cortices, rostral 1/3 of the dorsal anterior cingulate cortex) primarily project to the perirhinal and lateral entorhinal cortices. Projections from the remaining cingulate areas preferentially target the postrhinal and medial entorhinal cortices as well as the presubiculum and parasubiculum. At a more detailed level the projections show differences in topographical specificities according to their site of origin within the cingulate cortex suggesting the functional contribution of cingulate areas may differ at an individual level. This organization of the cingulate-parahippocampal projections relates to the overall organization of postulated parallel parahippocampal-hippocampal processing streams mediated through the lateral and medial entorhinal cortex respectively. The mid-rostrocaudal part of the dorsal anterior cingulate cortex appears to be connected to both networks as well as to rostral and caudal parts of the cingulate cortex. This region may therefore responsible for integrating information across these specific networks.     

Distribution of hippocampal CA1 and subicular efferents in the prefrontal cortex of the rat studied by means of anterograde transport of Phaseolus vulgaris-leucoagglutinin.

Projections of the hippocampal formation to the prefrontal cortex were visualized in the rat by means of the anterograde tracer Phaseolus vulgaris-leucoagglutinin. These projections distribute only to the prelimbic and the medial orbital cortices and arise exclusively from restricted portions of field CA1 of the Ammon's horn and the subiculum. The most dorsal portion of CA1 does not contribute fibers to this projection. In the subiculum, its origin is restricted to the proximal half, i.e., the portion that directly borders field CA1. Fibers from field CA1 and the subiculum have comparable distribution patterns in the prelimbic and medial orbital cortices. The density and distribution in the prefrontal cortex of the projections from the proximal portion of the subiculum depends on the location of the injections along the dorsoventral axis of the hippocampal formation: the intermediate portion of the subiculum projects more densely and diffusely than its dorsal and ventral portions. In the prelimbic cortex, labeled fibers are present in all layers, showing marked morphological differences in deep versus superficial layers. In layers V and VI, most of the fibers are vertically oriented, while in layers II and III they are short and oriented towards the pial surface. Although no clear differences in terminal distribution were observed along the rostrocaudal extent of the prelimbic cortex, its dorsal and ventral portions show different innervation patterns. In the ventral portion of the prelimbic cortex, varicose fibers and terminal arborizations were present in all cortical layers, deep (V and VI) as well as superficial (II and III). In its dorsal part, the innervation was less dense and mostly present in the deep layers (V and VI). The fiber and terminal distribution in the medial orbital cortex was diffuse in all layers with a slight preference for layers deep to layer II.     

Mediodorsal nucleus: areal, laminar, and tangential distribution of afferents and efferents in the frontal lobe of rhesus monkeys

The terminal distribution of thalamic afferents in primate prefrontal cortex has never been examined in any detail. In the present study, WGA-HRP was injected into major subdivisions of the mediodorsal nucleus (MD) in the rhesus monkey in order to determine 1) The areal distribution of MD projections, 2) the layer(s) in which MD afferents terminate, 3) the tangential pattern of the MD axonal terminals, 4) the cells of origin of the reciprocal corticothalamic pathway, and 5) the degree of reciprocity between the corticothalamic and thalamocortical pathways in the different regions of the prefrontal cortex. As expected on the basis of retrograde degeneration and transport studies, injections centered in the magnocellular (MDmc) subnucleus of MD labeled cells and terminals in the ventral and medial prefrontal cortex. Injections involving ventral MDmc labeled the more lateral of these areas (Walker's areas 11 and 12); injections of the dorsal MDmc labeled the ventromedial regions (areas 13 and 14). In contrast, injections involving mainly the lateral, parvicellular (MDpc) moiety labeled cells and terminals in dorsolateral and dorsomedial areas (Walker's 46, 9, and 8B). Area 8A was labeled most prominently when injections included the multiform portion of MD (MDmf) and area 10 had connections with anterior portions of MD. A dorsal-ventral topography for MDpc exists with dorsal MDpc labeling dorsal and dorsomedial prefrontal areas and ventral MDpc labeling dorsolateral prefrontal cortex. Our findings with respect to MD are consistent with a nucleus-to-field organization of its thalamocortical projection system. Outside of the traditional boundaries of prefrontal cortex, lateral MD projections extended to the supplementary motor area (SMA) and the dorsal part of the anterior cingulate (AC) whereas the medial MD projection targeted the ventromedial cingulate cortex and spared SMA. In addition, a few labeled cells and sparse terminals were found in the inferior parietal lobule, the superior temporal sulcus, and the anterior part of the insula after injections that involved the medial part of MD. Labeled terminals were invariably confined to layer IV and adjacent deep layer III. No terminal label was ever observed in layers I, II, superficial III, V, or VI in any part of the cerebral cortex following injections confined to any part of MD.(ABSTRACT TRUNCATED AT 400 WORDS)     

Common cortical and subcortical targets of the dorsolateral prefrontal and posterior parietal cortices in the rhesus monkey: evidence for a distributed neural network subserving spatially guided behavior

Common efferent projections of the dorsolateral prefrontal cortex and posterior parietal cortex were examined in 3 rhesus monkeys by placing injections of tritiated amino acids and HRP in frontal and parietal cortices, respectively, of the same hemisphere. Terminal labeling originating from both frontal and parietal injection sites was found to be in apposition in 15 ipsilateral cortical areas: the supplementary motor cortex, the dorsal premotor cortex, the ventral premotor cortex, the anterior arcuate cortex (including the frontal eye fields), the orbitofrontal cortex, the anterior and posterior cingulate cortices, the frontoparietal operculum, the insular cortex, the medial parietal cortex, the superior temporal cortex, the parahippocampal gyrus, the presubiculum, the caudomedial lobule, and the medial prestriate cortex. Convergent terminal labeling was observed in the contralateral hemisphere as well, most prominently in the principal sulcal cortex, the superior arcuate cortex, and the superior temporal cortex. In certain common target areas, as for example the cingulate cortices, frontal and parietal efferents terminate in an array of interdigitating columns, an arrangement much like that observed for callosal and associational projections to the principal sulcus (Goldman-Rakic and Schwartz, 1982). In other areas, frontal and parietal terminals exhibit a laminar complementarity: in the depths of the superior temporal sulcus, prefrontal terminals are densely distributed within laminae I, III, and V, whereas parietal terminals occupy mainly laminae IV and VI directly below the prefrontal bands. Subcortical structures also receive apposing or overlapping projections from both prefrontal and parietal cortices. The dorsolateral prefrontal and posterior parietal cortices project to adjacent, longitudinal domains of the neostriatum, as has been described previously (Selemon and Goldman-Rakic, 1985); these projections are also found in close apposition in the claustrum, the amygdala, the caudomedial lobule, and throughout the anterior medial, medial dorsal, lateral dorsal, and medial pulvinar nuclei of the thalamus. In the brain stem, both areas of association cortex project to the intermediate layers of the superior colliculus and to the midline reticular formation of the pons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Topography of descending projections from anterior insular and medial prefrontal regions to the lateral habenula of the epithalamus in the rat

The epithalamic lateral nucleus of the habenula (LHb) plays a key role in regulating firing of dopamine and serotonin neurons in the midbrain and is thereby involved in various cognitive and affective behaviors. It is not yet clear, however, from where the LHb receives cognitive and affective information relevant to its regulation of the midbrain monoaminergic systems. The prefrontal cortex would be among the ideal sources. Here, using anterograde and retrograde tracer injections in the rat brain, we characterized the topography of the corticohabenular projections. Following injections of cholera toxin subunit B into the LHb, retrogradely labeled neurons were produced in the anterior insular, cingulate, prelimbic and infralimbic cortices. Consistent with this retrograde tracing, injections of biotinylated dextran amine (BDA) into these cortical regions labeled robust terminals in the LHb. Our quantification of the BDA-impregnated varicosities revealed that projections from the anterior insula terminated mainly in the intersection regions of the lateral and ventral two-thirds of the LHb, while projections from the cingulate cortex terminated mainly in the lateral two-thirds of the LHb. By comparison, BDA-labeled terminals originating from the medial prefrontal regions were contained mainly in the medial plus ventral one-third of LHb. Based on these data, we hypothesize that LHb provides a link for conveying cognitive and affective information from prefrontal and insular regions to the midbrain monoaminergic centers.     

The organization of the thalamocortical connections of the mediodorsal thalamic nucleus in the rat, related to the ventral forebrain-prefrontal cortex topography.

The medial and central segments of the mediodorsal nucleus of the thalamus (MD) receive afferents from the ventral forebrain, including the piriform cortex, the ventral pallidum, and the amygdaloid complex. Because MD is reciprocally interconnected with prefrontal and agranular insular cortical areas, it provides a relay of ventral forebrain activity to these cortical areas. However, there are also direct projections from the piriform cortex and the amygdala to the prefrontal and agranular insular cortices. This study addresses whether this system has a "triangular" organization, such that structures in the ventral forebrain project to interconnected areas in MD and the prefrontal/insular cortex. The thalamocortical projections of MD have been studied in experiments with injections of retrograde tracers into prefrontal or agranular insular cortical areas. In many of the same experiments, projections from the ventral forebrain to MD and to the prefrontal/insular cortex have been demonstrated with anterograde axonal tracers. The connections of the piriform cortex (PC) with MD and the prefrontal/insular cortex form an organized triangular system. The PC projections to the central and medial segments of MD and to the lateral orbital cortex (LO) and the ventral and posterior agranular insular cortices (AIv and AIp) are topographically organized, such that more caudal parts of PC tend to project more medially in MD and more caudally within the orbital/insular cortex. The central and medial portions of MD also send matching, topographically organized projections to LO, AIv and AIp, with more medial parts of MD projecting further caudally. The anterior cortical nucleus of the amygdala (COa) also projects to the dorsal part of the medial segment of MD and to its cortical targets, the medial orbital area (MO) and AIp. The projections of the basal/accessory basal amygdaloid nuclei to MD and to prefrontal cortex, and from MD to amygdaloceptive parts of prefrontal cortex, are not as tightly organized. Amygdalothalamic afferents in MD are concentrated in the dorsal half of the medial segment. Cells in this part of the nucleus project to the amygdaloceptive prelimbic area (PL) and AIp. However, other amygdaloceptive prefrontal areas are connected to parts of MD that do not receive fibers from the amygdala. Ventral pallidal afferents are distributed to all parts of the central and medial segments of MD, overlapping with the fibers from the amygdala and piriform cortex. Fibers from other parts of the pallidum, or related areas such as the substantia nigra, pars reticulata, terminate in the lateral and ventral parts of MD, where they overlap with inputs from the superior colliculus and other brainstem structures.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prefrontal cortex in the rat: projections to subcortical autonomic, motor, and limbic centers

This paper describes the quantitative areal and laminar distribution of identified neuron populations projecting from areas of prefrontal cortex (PFC) to subcortical autonomic, motor, and limbic sites in the rat. Injections of the retrograde pathway tracer wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) were made into dorsal/ventral striatum (DS/VS), basolateral amygdala (BLA), mediodorsal thalamus (MD), lateral hypothalamus (LH), mediolateral septum, dorsolateral periaqueductal gray, dorsal raphe, ventral tegmental area, parabrachial nucleus, nucleus tractus solitarius, rostral/caudal ventrolateral medulla, or thoracic spinal cord (SC). High-resolution flat-map density distributions of retrogradely labelled neurons indicated that specific PFC regions were differentially involved in the projections studied, with medial (m)PFC divided into dorsal and ventral sectors. The percentages that WGA-HRP retrogradely labelled neurons composed of the projection neurons in individual layers of infralimbic (IL; area 25) prelimbic (PL; area 32), and dorsal anterior cingulate (ACd; area 24b) cortices were calculated. Among layer 5 pyramidal cells, approximately 27.4% in IL/PL/ACd cortices projected to LH, 22.9% in IL/ventral PL to VS, 18.3% in ACd/dorsal PL to DS, and 8.1% in areas IL/PL to BLA; and 37% of layer 6 pyramidal cells in IL/PL/ACd projected to MD. Data for other projection pathways are given. Multiple dual retrograde fluorescent tracing studies indicated that moderate populations (<9%) of layer 5 mPFC neurons projected to LH/VS, LH/SC, or VS/BLA. The data provide new quantitative information concerning the density and distribution of neurons involved in identified projection pathways from defined areas of the rat PFC to specific subcortical targets involved in dynamic goal-directed behavior.     

Organization of subcortical pathways for sensory projections to the limbic cortex. I. Subcortical projections to the medial limbic cortex in the rat

Subcortical afferent projections to the medial limbic cortex were examined in the rat by the use of retrograde axonal transport of horseradish peroxidase. Small iontophoretic injections of horseradish peroxidase were placed at various locations within the dorsal and ventral cingulate areas, the dorsal agranular and ventral granular divisions of the retrosplenial cortex and the presubiculum. Somata of afferent neurons in the thalamus and basal forebrain were identified by retrograde labeling. Each of the anterior thalamic nuclei was found to project to several limbic cortical areas, although not with equal density. The anterior dorsal nucleus projects primarily to the presubiculum and ventral retrosplenial cortex; the anterior ventral nucleus projects to the retrosplenial cortex and the presubiculum with apparently similar densities; and the anterior medial nucleus projects primarily to the cingulate areas. The projections from the lateral dorsal nucleus to these limbic cortical areas are organized in a loose topographic fashion. The projection to the presubiculum originates in the most dorsal portion of the lateral dorsal nucleus. The projection to the ventral retrosplenial cortex originates in rostral and medial portions of the nucleus, whereas afferents to the dorsal retrosplenial cortex originate in caudal portions of the lateral dorsal nucleus. The projection to the cingulate originates in the ventral portion of the lateral dorsal nucleus. Other projections from the thalamus originate in the intralaminar and midline nuclei, including the central lateral, central dorsal, central medial, paracentral, reuniens, and paraventricular nuclei, and the ventral medial and ventral anterior nuclei. In addition, projections to the medial limbic cortex from the basal forebrain originate in cells of the nucleus of the diagonal band. Projections to the presubiculum also originate in the medial septum. These results are discussed in regard to convergence of sensory and nonsensory information projecting to the limbic cortex and the types of visual and other sensory information that may be relayed to the limbic cortex by these projections.     

Anatomic organization of basoventral and mediodorsal visual recipient prefrontal regions in the rhesus monkey

The sources of ipsilateral cortical afferent projections to basoventral and mediodorsal prefrontal cortices that receive some visual input were studied with retrograde tracers (horseradish peroxidase or fluorescent dyes) in eight rhesus monkeys. The basoventral regions injected with tracers included basal (orbital) areas 11 and 12, lateral area 12, and ventral area 46. The mediodorsal regions included portions of medial area 32 and the caudal part of dorsal area 8. These sites represent areas within basoventral and mediodorsal prefrontal cortices that show a gradual increase in architectonic differentiation in a direction from the least differentiated orbital and medial limbic cortices toward the most differentiated cortices in the arcuate concavity. The results showed that the visual input to basoventral and mediodorsal prefrontal cortices originated largely in topographically distinct visual areas. Thus, basoventral sites received most of their visual cortical projections from the inferior temporal cortex. The rostral inferior temporal region was the predominant source of visual projections to orbital prefrontal sites, whereas lateral area 12 and ventral area 46 also received projections which were found more caudally. In contrast, mediodorsal prefrontal sites received most of their visual projections from dorsolateral and dorsomedial visual areas. The cells of origin were located in rostromedial visual cortices after injection of retrograde tracers in area 32 and in more caudal medial and dorsolateral visual areas after injection in caudal area 8. The latter also received substantial projections from visuomotor regions in the caudal portion of the lateral bank of the intraparietal sulcus. These results suggest that the basoventral prefrontal cortices are connected with ventral visual areas implicated in pattern recognition and discrimination, whereas the mediodorsal cortices are connected with medial and dorsolateral occipital and parietal areas associated with visuospatial functions. In addition, the prefrontal areas studied received projections from auditory and/or somatosensory cortices, from areas associated with more than one modality, and from limbic regions. Orbital area 12 seemed to be a major target of projections from somatosensory cortices and the rostral portion of medial area 32 received substantial projections from auditory cortices. The least architectonically differentiated areas (orbital area 11 and medial area 32) had more widespread corticocortical connections, including strong links with limbic cortices.(ABSTRACT TRUNCATED AT 400 WORDS)     

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 and efferent connections of the olfactory bulbs in the lizard Podarcis hispanica.

The connections of the olfactory bulbs of Podarcis hispanica were studied by tract-tracing of injected horseradish peroxidase. Restricted injections into the main olfactory bulb (MOB) resulted in bilateral terminallike labeling in the medial part of the anterior olfactory nucleus (AON) and in the rostral septum, lateral cortex, nucleus of the lateral olfactory tract, and ventrolateral amygdaloid nucleus. Bilateral retrograde labeling was found in the rostral lateral cortex and in the medial and dorsolateral AON. Ipsilaterally the dorsal cortex, nucleus of the diagonal band, lateral preoptic area, and dorsolateral amygdala showed labeled cell bodies. Retrogradely labeled cells were also found in the midbrain raphe nucleus. Results from injections into the rostral lateral cortex and lateral olfactory tract indicate that the mitral cells are the origin of the centripetal projections of the MOB. Injections in the accessory olfactory bulb (AOB) produced ipsilateral terminallike labeling of the ventral AON, bed nucleus of the accessory olfactory tract, central and ventromedial amygdaloid nuclei, medial part of the bed nucleus of the stria terminalis, and nucleus sphericus. Retrograde labeling of neurons was observed ipsilaterally in the bed nucleus of the accessory olfactory tract and stria terminalis, in the central amygdaloid nucleus, dorsal cortex, and nucleus of the diagonal band. Bilateral labeling of somata was found in the ventral AON, the nucleus sphericus (hilus), and in the mesencephalic raphe nucleus and locus coeruleus. Injections into the dorsal amygdala showed that the mitral neurons are the cells of origin of the AOB centripetal projections. Reciprocal connections are present between AOB and MOB. To our knowledge, this is the first study to address the afferent connections of the olfactory bulbs in a reptile. On the basis of the available data, a discussion is provided of the similarities and differences between the reptilian and mammalian olfactory systems, as well as of the possible functional role of the main olfactory connections in reptiles.