Cortical,thalamic, and amygdaloid connections of the anterior and posterior insular cortices

Cortical, thalamic, and amygdaloid projections of the rat anterior and posterior insular cortices were examined using the anterograde transport of biocytin. Granular and dysgranular posterior insular areas between bregma and 2 mm anterior to bregma projected to the gustatory thalamic nucleus. Granular cortex projected to the subjacent dysgranular cortex which in turn projected to the agranular (all layers) and granular cortices (layers I and VI). Both granular and dysgranular posterior areas projected heavily to the dysgranular anterior insular cortex. Agranular posterior insular cortex projected to medial mediodorsal nucleus, agranular anterior insular and infralimbic cortices as well as granular and dysgranular posterior insula. No projections to the amygdala were observed from posterior granular cortex, although dysgranular cortex projected to the lateral central nucleus, dorsolateral lateral nucleus, and posterior basolateral nucleus. Agranular projections were similar, although they included medial and lateral central nucleus and the ventral lateral nucleus. Dysgranular anterior insular cortex projected to lateral agranular frontal cortex and granular and dysgranular posterior insular regions. Agranular anterior insular cortex projected to the dysgranular anterior and prelimbic cortices. Anterior insuloamygdaloid projections targeted the rostral lateral and anterior basolateral nuclei with sparse projections to the rostral central nucleus. The data suggest that the anterior insula is an interface between the posterior insular cortex and motor cortex and is connected with motor-related amygdala regions. Amygdaloid projections from the posterior insular cortex appear to be organized in a feedforward parallel fashion targeting all levels of the intraamygdaloid connections linking the lateral, basolateral, and central nuclei . J. Comp. Neurol. 399:440–468, 1998. © 1998 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.     

Cytoarchitecture and neural afferents of orbitofrontal cortex in the brain of the monkey.

The orbitofrontal cortex of the monkey can be subdivided into a caudal agranular sector, a transitional dysgranular sector, and an anterior granular sector. The neural input into these sectors was investigated with the help of large horseradish peroxidase injections that covered the different sectors of orbitofrontal cortex. The distribution of retrograde labeling showed that the majority of the cortical projections to orbitofrontal cortex arises from a restricted set of telencephalic sources, which include prefrontal cortex, lateral, and inferomedial temporal cortex, the temporal pole, cingulate gyrus, insula, entorhinal cortex, hippocampus, amygdala, and claustrum. The posterior portion of the orbitofrontal cortex receives additional input from the piriform cortex and the anterolateral portion from gustatory, somatosensory, and premotor areas. Thalamic projections to the orbitofrontal cortex arise from midline and intralaminar nuclei, from the anteromedial nucleus, the medial dorsal nucleus, and the pulvinar nucleus. Orbitofrontal cortex also receives projections from the hypothalamus, nucleus basalis, ventral tegmental area, the raphe nuclei, the nucleus locus coeruleus, and scattered neurons of the pontomesencephalic tegmentum. The non-isocortical (agranular-dysgranular) sectors of orbitofrontal cortex receive more intense projections from the non-isocortical sectors of paralimbic areas, the hippocampus, amygdala, and midline thalamic nuclei, whereas the isocortical (granular) sector receives more intense projections from the dorsolateral prefrontal area, the granular insula, granular temporopolar cortex, posterolateral temporal cortex, and from the medial dorsal and pulvinar thalamic nuclei. Retrograde labeling within cingulate, entorhinal, and hippocampal cortices was most pronounced when the injection site extended medially into the dysgranular paraolfactory cortex of the gyrus rectus, an area that can be conceptualized as an orbitofrontal extension of the cingulate complex. These observations demonstrate that the orbitofrontal cortex has cytoarchitectonically organized projections and that it provides a convergence zone for afferents from heteromodal association and limbic areas. The diverse connections of orbitofrontal cortex are in keeping with the participation of this region in visceral, gustatory, and olfactory functions and with its importance in memory, motivation, and epileptogenesis.     

Neural inputs into the temporopolar cortex of the rhesus monkey

Temporopolar cortex (TP) can be subdivided into agranular, dysgranular, and granular components. The telencephalic input into the temporopolar cortex arises from the orbitofrontal and medial frontal regions, modality-specific visual and auditory association areas, paralimbic regions, the piriform olfactory cortex, the hippocampus, the amygdala, the claustrum, and the basal forebrain. Afferents from limbic and paralimbic regions are directed mostly to the agranular and dysgranular sectors of the temporal pole, whereas afferents from isocortical association areas are distributed predominantly within the granular sector. The temporopolar cortex provides a site for the potential convergence of sensory and limbic inputs. Auditory inputs predominate in the dorsolateral part of the temporopolar cortex whereas visual inputs become prominent only in the ventral portions of this region. Olfactory inputs are directed mostly to the medial parts of the temporal pole. These medial parts also receive more extensive projections from the amygdaloid nuclei.     

Cortical Granularity Shapes the Organization of Afferent Paths to the Amygdala and Its Striatal Targets in Nonhuman Primate

The prefrontal cortex (PFC) and insula, amygdala, and striatum form interconnected networks that drive motivated behaviors. We previously found a connectional trend in which granularity of the ventromedial and orbital PFC/insula predicted connections to the amygdala, and also the breadth of amygdalo-striatal efferents, including projections beyond the “classic” ventral striatum. To further interrogate connectional relationships among the cortex, amygdala, and striatum, and to further define the “limbic” (amygdala-recipient) striatum, we conducted tract tracing studies in two cohorts of macaques (male n = 14, female n = 1). We focused on the cortico-amygdalo-striatal (indirect) and cortico-“limbic” striatal (direct) paths originating in the entire PFC and insula. Larger datasets and a quantitative approach revealed “cortical rules” in which cortical granularity predicts the complexity and location of projections to both the basal nucleus of the amygdala and striatum. Remarkably, projections from “cortical-like” basal nucleus to the striatum followed similar patterns. In both “direct” and “indirect” paths to the “limbic” striatum, agranular cortices formed a “foundational,” broad projection, and were joined by inputs from progressively more differentiated cortices. In amygdalo-striatal paths, the ventral basal nucleus was the “foundational” input, with progressively more dorsal basal nucleus regions gradually adding inputs as the “limbic” striatum extended caudally. Together, the “indirect” and “direct” paths followed consistent principles in which cortical granularity dictated the strength and complexity of projections at their targets. Cluster analyses independently confirmed these connectional trends, and also highlighted connectional features that predicted termination in specific subregions of the basal nucleus and “limbic” striatum.SIGNIFICANCE STATEMENT The “limbic” system broadly refers to brain circuits that coordinate emotional responses. Here, we investigate circuits of the amygdala, which are involved in coding the emotional value of external cues, and their influence on the striatum. Regions of prefrontal cortex (PFC) and insula form gradients of overlapping inputs to the amygdala''s basal nucleus, which feed forward to the striatum. Direct cortical inputs to these “amygdala-recipient” striatal areas are surprisingly organized according to similar principles but subtly shift from the “classic” ventral striatum to the caudal ventral striatum. Together, these distinct subsystems, cortico-amygdalo-striatal circuits and direct cortico-striatal circuits, provide substantial opportunity for different levels of internal, sensory, and external experiences to be integrated within the striatum, a major motor-behavioral interface.     

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.     

Connections of the amygdala of the rat. IV: Corticoamygdaloid and intraamygdaloid connections as studied with axonal transport of horseradish peroxidase

The corticoamygdaloid and intraamygdaloid projections of the rat were studied by the use of retrograde transport of horseradish peroxidase (HRP). Observations based on anterograde transport of the enzyme were exploited to determine the course of the intrinsic connections. The HRP was injected stereotactically by means of iontophoresis. Most of the amygdaloid nuclei were selectively injected, and all but a few were reached by more than one approach. The vast majority of corticoamygdaloid fibers was found to originate in cortical areas defined as allocortical (Stephan, 1975). From the medial frontal cortex the central amygdaloid nucleus (AC) receives a hitherto undescribed projection originating in the tenia tecta; and both the AC and the lateral amygdaloid nucleus (AL) receive fibers from the prelimbic and infralimbic areas. The anterior cingulate area entertains a weak connection with the basolateral amygdaloid nucleus (BL). As to the insular cortex, the posterior agranular insular area projects to all amygdaloid subdivisions; the BL, AC, and the anterior cortical nucleus (COa) receive, in addition, fibers from the ventral agranular area. The prepyriform cortex connects with the entire amygdala except the medial nucleus (Am) The amygdala receives afferents from a transitional area between the amygdala and the entorhinal area. The entorhinal area proper is related to the amygdala via projections from the ventral part of the lateral entorhinal area to the AL and from the dorsal part of the lateral entorhinal area to the BL. The former nucleus also receives fibers from the perirhinal region. Additional amygdalopetal connections from the hippocampal region include a previously undescribed projection from the temporal two-thirds of CA1 to the AL and BL and to the posterior cortical nucleus (COp) with the adjacent periamygdaloid cortex (PAC). The subiculum projects to the AL, and more modestly to other amygdaloid nuclei There is an extensive network of intraamygdaloid connections, the Am and AC being the only nuclei not giving rise to intrinsic fibers.     

Connectivity and cytoarchitecture of the ventral telencephalon in the salamander Plethodon shermani

The cytoarchitecture and axonal connection pattern of centers in the ventral telencephalon of the salamander Plethodon shermani were studied using biocytin for anterograde and retrograde labeling of cell groups, as well as by intracellular injections. Application of biocytin to the main and accessory olfactory bulbs identified the olfactory pallial regions and the vomeronasal portion of the amygdala, respectively. According to our results, the amygdala of Plethodon is divided into (1) a rostral part projecting to visceral and limbic centers and receiving afferents from the dorsal thalamus, and (2) a caudal part receiving accessory olfactory input. The striatopallial transition area (SPTA) lies rostrodorsally to the caudal (vomeronasal) amygdala and is similar in connections and possibly in function. The rostral striatum has few descending projections to the medulla, whereas the intermediate striatum sends strong projections to the tegmentum and medulla. The caudal striatum has strong ascending projections to the striatum and descending projections to the ventral hypothalamus. The dendritic trees of neurons labeled below the striatum and in the SPTA spread laterally from the soma, whereas dendrites of striatal neurons converge into the laterally situated striatal neuropil. In the caudal amygdala, three distinct types of neurons are found differing in dendritic arborization. It is concluded that, hodologically, the rostral part of the urodele amygdala corresponds to the central and basolateral amygdala and the caudal part to the cortical/medial amygdala of mammals. The urodele striatum is divided into a rostral striatum proper, an intermediate dorsal pallidum, and a caudal part, with distinct connections described here for the first time in a vertebrate.     

Insula of the old world monkey. III: Efferent cortical output and comments on function

The insula sends neural efferents to cortical areas from which it receives reciprocal afferent projections. A collective consideration of afferents and efferents indicates that the insula has connections with principal sensory areas in the olfactory, gustatory, somesthetic (SI and SII), and auditory AI and AII) modalities. There are additional connections with association areas for the visual (TEm), auditory (supratemporal plane), and somesthetic (posterior parietal cortex) modalities; with parameter cortex (area 6 and perhaps MII); with polymodal association cortex; and with a wide range of paralimbic areas in the orbital, temporopolar, and cingulate areas. The topographic distribution of these connections suggests that the posterodorsal insula is specialized for auditory-somesthetic-skeletomotor function whereas the anteroventral insula is related to olfactory-gustatory-autonomic function. Most of the insula, especially its anteroventral portions, have extensive interconnections with limbic structures. Through its connections with the amygdala, the insula provides a pathway for somatosen-sory, auditory, gustatory, olfactory, and visceral sensations to reach the limbic system. The cortical areas connected with the granular sector of the insula are also granular in architecture whereas virtually all the connections of the agranular insula arise from allocortical, agranular, or dysgranular areas. Thus, there is a correspondence between the architecture of insular sectors and the areas with which they have connections. The insula is heavily interconnected with temporopolar and lateral orbital areas. Furthermore, many cortical connections of the lateral orbital cortex are quite similar to those of the insula. These common connectivity patterns support the conclusion, based on architectonic observations, that the insulo-orbito-tempo-ropolar component of the paralimbic brain should be considered as an integrated unit of cerebral organization.     

Architectural subdivisions of medial and orbital frontal cortices in the marmoset monkey (Callithrix jacchus)

Although the common marmoset has become a model for the study of several neurological conditions that affect the frontal lobe, knowledge of the boundaries of the areas located in the orbital and medial frontal regions has remained incomplete. Here we examined histological sections stained for myelin, Nissl substance, and cytochrome oxidase, allowing identification of likely homologues of most of the architectural fields defined in Old World monkeys. Ventrally, we identified three granular fields at or near the frontal pole (area 10, and the medial and lateral subregions of area 11), and two granular fields along the lateral margin of the orbitofrontal cortex (medial and orbital subdivisions of area 12). More caudal and medially, dysgranular and agranular cortices included four subdivisions of area 13 as well as rostral and caudal subdivisions of area 14 (at the ventromedial convexity). The ventral frontotemporal transition encompassed at least two subdivisions of agranular insular cortex, as well as the likely homologues of the gustatory cortices. Most of the medial surface was encompassed by area 10 (which projected a caudomedial finger‐like extension toward the subgenual cortex), together with a relatively large dysgranular area 32 and an agranular area 25 (in subgenual cortex). Finally, the caudal limit of the medial frontal cortex included two fields of agranular cingulate cortex (areas 24a and 24b). These findings enhance our understanding of the architectural organization of the marmoset frontal cortex and highlight a highly conserved basic organization across simian primates, allowing the informed interpretation of experimental neurological studies. J. Comp. Neurol. 514:11–29, 2009. © 2009 Wiley‐Liss, Inc.     

Sensory and premotor connections of the orbital and medial prefrontal cortex of macaque monkeys

Sensory and premotor inputs to the orbital and medial prefrontal cortex (OMPFC) were studied with retrograde axonal tracers. Restricted areas of the lateral and posterior orbital cortex had specific connections with visual-, somatosensory-, olfactory-, gustatory-, and visceral-related structures. More medial areas received few direct sensory inputs. Within the lateral and posterior orbital cortex, area 121 received a substantial projection from visual areas in the inferior temporal cortex (TE). Area 12m received somatosensory input from face, digit, or forelimb regions in the opercular part of area 1–2, in area 7b, in the second somatosensory area (SII), and in the anterior infraparietal area (AIP). Areas 13m and 131 also received a projection from the opercular part of areas 1–2 and 3b. The posteromedial and lateral agranular insular areas (Iapm and Ial, respectively) received fibers from the ventral part of the parvicellular division of the ventroposterior medial nucleus of the thalamus (VPMpc) that may represent a visceral afferent system. The dorsal part of VPMpc projected to the adjacent gustatory cortex. These restricted inputs from several sensory modalities and the convergent corticocortical connections to orbital areas 13l and 13m suggest a network related to feeding. The OMPFC was also connected to premotor cortex in ventral area 6 (areas 6va and 6vb), in cingulate area 24c, and probably in the supplementary eye field. Area 6va projected to area 12m, whereas a region of area 6vb projected to area 131. The region of the supplementary eye field projected to areas 121, 120, and 12r. Area lal received fibers from area 24c. Lighter and more diffuse projections also reached wider areas of the OMPFC. For example, injections in several orbital areas labeled a few cells scattered through the anterior part of area TE and the superior temporalrus. There was also a projection to the intermediate agranular insular area (Iai) and to areas 13a and 12o from the apparently multimodal areas in the superior temporal sulcus and gyrus. © 1995 Wiley-Liss, Inc.     

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)     

Cortical and subcortical afferents to the amygdala of the rhesus monkey (Macaca mulatta)

The afferent projections to the primate amygdala were studied using horseradish peroxidase. The potential advantages of this technique are discussed compared with those previously used to determine amygdaloid afferents. The findings indicate that certain agranular or dysgranular cortical regions may project directly to the amygdala: in particular, the orbital frontal cortex, anterior cingulate gyrus, subcallosal gyrus, temporal pole and anterior insula. These projections probably terminate predominantly in either the lateral or accessory basal nuclei. Other cortical projections from the inferotemporal and superior temporal gyri are described. Evidence was found for a heavy projection from the superior temporal sulcus to the lateral nucleus. Subcortical afferents were found from the hypothalamus, substantia innominata, diagonal band, thalamus, periaqueductal central gray, peripeduncular nucleus and from a band of cells extending medially from the peripeduncular nucleus to the midline, just ventral to the thalamus. In the thalamus, labelled cells were restricted to the non-specific nuclei, and were common in the rostral midline nuclei. No projection was observed from the dorsomedial nucleus of the thalamus. We discuss the implications of these results for interpreting the functions of the amygdala.     

Differential connections of the temporal pole with the orbital and medial prefrontal networks in macaque monkeys

Previous studies indicate that the orbital and medial prefrontal cortex (OMPFC) is organized into "orbital" and "medial" networks, which have distinct connections with cortical, limbic, and subcortical structures. In this study, retrograde and anterograde tracer experiments in monkeys demonstrated differential connections between the medial and orbital networks and the dorsal and ventral parts of the temporal pole. The dorsal part, including dysgranular and granular areas (TGdd and TGdg), is reciprocally connected with the medial network areas on the medial wall and gyrus rectus (areas 10m, 10o, 11m, 13a, 14c, 14r, 25, and 32) and on the lateral orbital surface (areas Iai and 12o). The strongest connections are with areas 10m (caudal part), 14c, 14r, 25, 32, and Iai. The agranular temporal pole (TGa) is connected with several areas, but most strongly with medial network area 25. The granular area around the superior temporal sulcus (TGsts) and the ventral dysgranular and granular areas (TGvd and TGvg) are reciprocally connected with the orbital network (especially areas 11l, 13b, 13l, 13m, Ial, Iam, and Iapm). TGsts is strongly connected with the entire orbital network, whereas areas TGvd and TGvg have lighter and more limited connections. Intrinsic connections within the temporal pole are also restricted to dorsal or ventral parts. Together with evidence that the dorsal and ventral temporal pole are differentially connected to auditory and visual areas of the superior and inferior temporal cortex, the results indicate separate connections between these systems and the medial and orbital prefrontal networks.     

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.     

Prefrontal cortical projections to the striatum in macaque monkeys: evidence for an organization related to prefrontal networks

The organization of projections from the prefrontal cortex (PFC) to the striatum in relation to previously defined "orbital" and "medial" networks within the PFC were studied in monkeys using anterograde and retrograde tracing techniques. The results indicate that the orbital and medial networks connect to different striatal regions. The ventromedial striatum (the medial caudate nucleus, accumbens nucleus, and ventral putamen) receives input predominantly from the medial PFC (mPFC) and orbital areas 12o, Iai, and 13a, which constitute the "medial" network. More specifically, caudal medial areas 32, 25, and 14r project to the medial edge of the caudate nucleus, accumbens nucleus, and ventromedial putamen, whereas rostral areas 10o, 10m, and 11m are restricted to the medial edge of the caudate. Projections from orbital areas 12o, 13a, and Iai extend more laterally into the lateral accumbens and the ventral putamen. Area 24 gives rise to a divided pattern of projections, including fibers to the ventromedial striatum, apparently from area 24b, and fibers to the dorsolateral striatum, apparently from area 24c. Other areas of orbital cortex (11l, 12m, 12l, 13m, 13l, Ial, and Iam) that constitute the "orbital" network project primarily to the central part of the rostral striatum. This region includes the central and lateral parts of the caudate nucleus, and the ventromedial putamen, on either side of the internal capsule. The results support the subdivision of the orbital and medial PFC into "medial" and "orbital" networks and suggest that the prefrontostriatal projections reflect the functional organization of the PFC rather than topographic location.     

Afferent connections of the amygdalopiriform transition area in the rat

The amygdalopiriform transition area (APir) is often considered part of the lateral entorhinal cortex (Entl). However, in contrast to Entl, APir densely innervates the central extended amygdala (EAc) and does not project to the dentate gyrus. In order to gain a more comprehensive understanding of these territories, the afferent connections of APir were examined in the rat with retrograde (cholera toxin B subunit or FluoroGold) and anterograde tracers (Phaseolus vulgaris leucoagglutinin) and compared to those of the neighboring Entl. The results suggest that APir and Entl are interconnected and receive topographically organized hippocampal projections. Both are targeted by the olfactory bulb, the piriform, posterior agranular insular and perirhinal cortices, the ventral tegmental area, dorsal raphe nucleus, and locus coeruleus. Most importantly, the data reveal that APir and Entl also have specific inputs and should be viewed as separate anatomical entities. The APir receives robust projections from structures affiliated with the EAc, including the anterior basomedial and posterior basolateral amygdaloid nuclei, the gustatory thalamic region, parasubthalamic nucleus, and parabrachial area. The Entl is a major recipient for amygdaloid projections from the medial part of the lateral nucleus and the caudomedial part of the basolateral nucleus. Moreover, the medial septum, subicular complex, nucleus reuniens, supramammillary region, and nucleus incertus, which are associated with the hippocampal system, preferentially innervate the Entl. These data underscore that APir processes olfactory and gustatory information and is tightly linked to EAc operations, suggesting that it may play a role in reward mechanisms, particularly in hedonic aspects of feeding.     

Amygdaloid projections to subcortical structures within the basal forebrain and brainstem in the rat and cat

The efferent fiber connections of the nuclei of the amygdaloid complex with subcortical structures in the basal telencephalon, hypothalamus, midbrain, and pons have been studied in the rat and cat, using the autoradiographic method for tracing axonal connections. The cortical and thalamic projections of these nuclei have been described in previous papers (Krettek and Price, ′77b,c). Although the subcortical connections of the amygdaloid nuclei are widespread within the basal forebrain and brain stem, the projections of each nucleus have been found to be well defined, and distinct from those of the other amygdaloid nuclei. The basolateral amygdaloid nucleus projects heavily to the lateral division of the bed nucleus of the stria terminalis (BNST), to the caudal part of the substantia innominata, and to the ventral part of the corpus striatum (nucleus accumbens and ventral putamen) and the olfactory tubercle; it projects more lightly to the lateral hypothalamus. The central nucleus also projects to the lateral division of the BNST and the lateral hypothalamus, but in addition it sends fibers to the lateral part of the substantia nigra and the marginal nucleus of the brachium conjunctivum. The basomedial nucleus has projections to the ventral striatum and olfactory tubercle which are similar to those of the basolateral nucleus, but it also projects to the core of the ventromedial hypothalamic nucleus and the premammillary nucleus, and to a central zone of the BNST which overlaps the medial and lateral divisions. The medial nucleus also projects to the core of the ventromedial nucleus and the premammillary nucleus, but sends fibers to the medial division of the BNST and does not project to the ventral striatum. The posterior cortical nucleus projects to the premammillary nucleus and to the medial division of the BNST, but a projection from this nucleus to the ventromedial nucleus has not been demonstrated. Projections to the “shell” of the ventromedial nucleus have been found only from the ventral part of the subiculum and from a structure at the junction of the amygdala and the hippocampal formation, which has been termed the amygdalo-hippocampal area (AHA). The AHA also sends fibers to the medial part of the BNST and the premammillary nucleus. Virtually no subcortical projections outside the amygdala itself have been demonstrated from the lateral nucleus, or from the olfactory cortical areas around the amygdala (the anterior cortical nucleus, the periamygdaloid cortex, and the posterior prepiriform cortex). However, portions of the endopiriform nucleus deep to the prepiriform cortex project to the ventral putamen, and to the lateral hypothalamus.     

An experimental study of the ventral striatum of the golden hamster. II. Neuronal connections of the olfactory tubercle

As part of an experimental study of the ventral striatum, the horseradish peroxidase (HRP) method was used to examine the afferent and efferent neuronal connections of the olfactory tubercle. Following iontophoretic applications or hydraulic injections of HRP in the tubercle, neurons labeled by retrograde transport of HRP were observed ipsilaterally in the telencephalon in the main olfactory bulb, the medial, lateral, ventral, and posterior divisions of the anterior olfactory nucleus, and in the orbital, ventral, and posterior agranular insular, primary olfactory, perirhinal, and entorhinal cortices. Labeled cells were also present in the basolateral, basomedial, anterior cortical, and posterolateral cortical amygdaloid nuclei, and bilaterally in the nucleus of the lateral olfactory tract. In the diencephalon, ipsilateral HRP-containing neurons were observed in the midline nuclei paraventricularis, parataenialis, and reuniens, and in the parafascicular intralaminar nucleus. Retrograde labeling was present in the ipsilateral brainstem in cells of the ventral tegmental area, substantia nigra, and dorsal raphe. Many of the above projections to the tubercle were found to be topographically organized. Anterograde axonal transport of HRP from the olfactory tubercle labeled terminal fields ipsilaterally in all parts of the anterior olfactory nucleus, in the ventral pallidum, and in the substantia nigra, pars reticulata. Contralaterally, terminal fields were present in the dorsal and lateral divisions of the anterior olfactory nucleus. The projections to the tubercle from the orbital, ventral, and posterior agranular insular, and perirhinal neocortices, intralaminar thalamus, and dopamine-containing areas of the ventral mesencephalon are analogous to the connections of the caudatoputamen, as are the efferents from the tubercle to the ventral globus pallidus and substantia nigra. These connections substantiate the recent suggestion that the olfactory tubercle is a striatal structure, and provide support for the ventral striatal concept. In the present study of the olfactory tubercle, and in the first study in this series on the nucleus accumbens, the ventral striatum was found to receive projections from a number of limbic system structures, including the main olfactory bulb, anterior olfactory nucleus, amygdala, hippocampus, and subiculum, and the entorhinal and primary olfactory cortices. These findings suggest that the ventral striatum is concerned with integrating limbic information into the striatal system.     

Efferent connections of the substantia innominata in the rat

The efferent connections of the substantia innominata (SI) were investigated employing the anterograde axonal transport of Phaseolus vulgaris leucoagglutinin (PHA-L) and the retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). The projections of the SI largely reciprocate the afferent connections described by Grove (J. Comp. Neurol. 277:315-346, '88) and thus further distinguish a dorsal and a ventral division in the SI. Efferents from both the dorsal and ventral divisions of the SI descend as far caudal as the ventral tegmental area, substantia nigra, and peripeduncular area, but projections to pontine and medullary structures appear to originate mainly from the dorsal SI. Within the amygdala and hypothalamus, which receive widespread innervation from the SI, the dorsal SI projects preferentially to the lateral part of the bed nucleus of the stria terminalis; the lateral, basolateral, and central nuclei of the amygdala; the lateral preoptic area; paraventricular nucleus of the hypothalamus; and certain parts of the lateral hypothalamus, prominently including the perifornical and caudolateral zones described previously. The ventral SI projects more heavily to the medial part of the bed nucleus of the stria terminalis; the anterior amygdaloid area; a ventromedial amygdaloid region that includes but is not limited to the medial nucleus; the lateral and medial preoptic areas; and the anterior hypothalamus. Modest projections reach the lateral hypothalamus, with at least a slight preference for the medial part of the region, and the ventromedial and arcuate hypothalamic nuclei. Both SI divisions appear to innervate the dorsomedial and posterior hypothalamus and the supramammillary region. In the thalamus, the subparafascicular, gustatory, and midline nuclei receive a light innervation from the SI, which projects more densely to the medial part of the mediodorsal nucleus and the reticular nucleus. Cortical efferents from at least the midrostrocaudal part of the SI are distributed primarily in piriform, infralimbic, prelimbic, anterior cingulate, granular and agranular insular, perirhinal, and entorhinal cortices as well as in the main and accessory olfactory bulbs. The cells of origin for many projections arising from the SI were identified as cholinergic or noncholinergic by combining the retrograde transport of WGA-HRP with histochemical and immunohistochemical procedures to demonstrate acetylcholinesterase activity or choline acetyltransferase immunoreactivity. Most of the descending efferents of the SI appear to arise primarily or exclusively from noncholinergic cells.(ABSTRACT TRUNCATED AT 400 WORDS)