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Topographically Specific Hippocampal Projections Target Functionally Distinct Prefrontal Areas in the Rhesus Monkey

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Topographically Specific Hippocampal Projections Target Functionally Distinct Prefrontal Areas in the Rhesus Monkey HIPPOCAMPUS 5:511-533 (1995) Topographically Specific Hippocampal Projections Target Functionally Distinct Prefrontal Areas in the Rhesus Monkey Helen Barbas1r2and Gene J. Blatt2 [Department of Health Sciences, Boston University and lJ2Departmentof Anatomy and Neurobiology, Boston University School of Medicine, Boston, Massachusetts ABSTRACT: The sources of ipsilateral projections from the hippocam- KEY WORDS: medial prefrontal cortex, orbitofrontal pal formation, the presubiculum, area 29a-c, and parasubiculum to me- cortex, memory, CA1, subiculum, .presubiculum, area dial, orbital, and lateral prefrontal cortices were studied with retrograde 29, lateral prefrontal cortex, working memory tracers in 27 rhesus monkeys. labeled neurons within the hippocampal formation (CA1, CA1’, prosubiculum, and subiculum) were found ros- trally, although some were noted throughout the entire rostrocaudal ex- tent of the hippocampal formation. Most labeled neurons in the hip- pocampal formation projected to medial prefrontal cortices, followed by orbital areas. In addition, there were differences in the topography of af- ferent neurons projecting to medial when compared with orbital cortices. Labeled neurons innervating medial cortices were found mainly in the The prefrontal cortex in the rhesus monkey is a large CA1’ and CA1 fields rostrally, but originated in the subicular fields cau- cortical cxpanse associated with complex cognitive, dally. In contrast, labeled neurons which innervated orbital cortices were mnemonic, and emotional processes (for rcvicws, see considerably more focal, emanating from the same relative position within Fuster, 1989; Barbas, 1995a). The functions of pre- a field throughout the rostrocaudal extent of the hippocampal formation. frontal areas are likely to depend on their connections In marked contrast to the pattern of projection to medial and orbital prefrontal cortices, lateral prefrontal areas received projections from only with other cortical and subcortical structures. Classically a few labeled neurons found mostly in the subicular fields. Lateral pre- known as polymodal, prefrontal cortices receive distrib- frontal cortices received the most robust projections from the pre- uted projections from areas associated with each of the subiculum and the supracallosal area 29a-c. Orbital, and to a lesser ex- sensory modalities but do not appear to be committed tent medial, prefrontal areas received projections from a smaller but to processing input from any single sensory modality significant number of neurons from the presubiculum and area 29a-c. Only a few labeled neurons were found in the parasubiculum, and most (for reviews, see Barbas, 1992, 19954. Rather, sensory projected to medial prefrontal areas. input to prefrontal areas appears to be linked to action The results suggest that functionally distinct prefrontal cortices receive (for rcvicws, scc Fustcr, 1990, 1993), a hypothesis sup- projections from different components of the hippocampal region. Medial ported by the close connectional association of prefrontal and orbital prefrontal cortices may have a role in long-term mnemonic cortices with the premotor and supplementary niotor processes similar to those associated with the hippocampal formation with which they are linked. Moreover, the preponderance of projection cortices (Matelli et al., 1986; Barbas and Pandya, 1987; neurons from the hippocampal formation innervating medial when com- Arikuni et al., 1988). In addition, prefrontal areas are pared with orbital prefrontal areas followed the opposite trend from what characterized hy the robust projections they receive from we had observed previously for the amygdala (Barbas and De Olmos limbic structures as notcd in classic studics (Nauta, [1990] (J Comp Neurol 301 :1-23). Thus, the hippocampal formation, as- 1971, 1972, 1979). Thc limbic system has been impli- sociated with mnemonic processes, targets predominantly medial pre- frontal cortices, whereas the amygdala, associated with emotional aspects cated in emotional and mncrnonic proccsscs, and its in- of memory, issues robust projections to orbital limbic cortices. Lateral put onto prefrontal areas is likely to have profound ef- prefrontal cortices receive robust projections from the presubiculum and fects on their function and on behavior (for review, see area 29a-c and sparse projections from the hippocampal formation. These Damasio, 1994). findings are consistent with the idea that the role of lateral prefrontal cortices in memory is distinct from that of either medial or orbital cor- Input from sensory and limbic structures to the var- tices. The results suggest that signals from functionally distinct limbic ious prefrontal areas is not uniform. The connectional structures to some extent follow parallel pathways to functionally distinct heterogcncity of prefrontal cortices is likely to underlie prefrontal cortices. 0 1995 Wiley-Liss, Inc. their functional specialization. Our previous studies sug- gest that the connectional organization of prefrontal cor- tices appears to depend on two major fixtors. One is Accepted for publication Scptcmber 11, 199.5. based on cortical type, and the other is based broadly Address correspondence and reprint requests to Helen Barbas, Boston on cortical region (for reviews, see Barbas, 1992, Harbas, University, 635 Commonwealth Ave., Room 431, Boston, MA 0221 5. 1995a). With regard to cortical type, prefrontal areas 0 1995 WLEY-LZSS, ZNC. 512 BARBAS AND BLATT vary widely, ranging from those which have three or four layers, structures to prefrontal cortices has not been clearly defined. The exemplified in transitional (limbic) cortices, to those which have hippocampus projects to some prefrontal areas (Rosene and Van six laycrs, which typify culaminate areas. Although input to eu- Hoesen, 1977; Goldman-Rakic et al., 1984; Morecraft et al., laminatc prefrontal areas is distributed, by comparison with the 1992), although the extent of its influence onto prefrontal cor- limbic areas it is considerably more focal. Thus, sensory input to tices is not known. Situated in the cemporal lobe behind the those eulaniinate prefrontal areas with the best laminar definition amygdala, the hippocampus has been implicated in specific as- originates from cortices associated with one or two modalities, in- pects of mnemonic processing distinct from the role of the amyg- trinsic input is from neighboring cortices, thalamic projections dala in emotive behavior (Zola-Morgan ct al., 1989b, 1991; for emanate primarily from the mediodorsal nucleus, and input from review, see Zola-Morgan and Squire, 1993). In this study we ad- limbic structures is sparse (for review, see Barbas, 1995a). In con- dressed several questions about the interface of the hippocampus trast, the structurally identified prefrontal limbic areas, situated with prefrontal cortices within the context of the structural at- on the caudal orbital and medial surfaces, have the most diverse tributes of both thc prefrontal cortex and the hippocampal re- connections among prefrontal areas. Thus, prefrontal limbic cor- gion. Which prefrontal areas receive projections from the hip- tices receive robust projections from cortical and subcortical lim- pocampus? Does the hippocampus have a regionally specific bic structures, from several modality-specific and polymodal cor- projectional relationship with distinct prefrontal cortical sectors, tices, and from a diverse set of thalamic nuclei (for review, see as was noted for the amygdala? Are there differences in the topog- Barbas, 1995a). raphy or number of hippocampal neurons projecting to the pre- The connections of prefrontal areas also vary broadly on a re- frontal limbic cortices on the medial or orbital surfaces and to eu- gional basis. Thus, prefrontal cortices situated on the medial and laminatc areas on the lateral surface? dorsolateral aspect of the cerebral hemisphere receive input asso- ciated with spatial aspects of the sensory environment and spatial memory. In contrast, prefrontal areas found on the basal and ven- trolateral aspect of the cerebral hemisphere process input related to the features of stimuli and their memory (Bauer and Fuster, Surgical Procedures 1976; Fuster et al., 1985; Barbas, 1988; Wilson et al., 1993). ‘I’here is less information on the regional organization of pro- Experiments were conducted on 27 rhesus monkeys (Macuca jections from limbic structures to functionally distinct prefrontal mulutta) according to the NIH Guide for the Care and Use of cortices. This information is important, because like sensory ar- Laboratory Animals (NIH publication 80-22, 1987). The animals cas, different limbic structures have functionally distinct attrib- were anesthetized with ketamine hydrochloride (10 mg/kg, intra- utes. For example, the amygdala and the hippocampus have dif- muscularly) followed by sodium pentnbarbital administered in- ferent roles in the emotional and mnemonic functions classically travenously through a femoral cathctcr until a surgical level of anes- associated with the limbic system (Nishijo et al., 1988; Zola- thesia was achieved. Additional anesthetic was administered during Morgan et al., 1989b, 1991; Davis, 1992). Projections from lim- surgery as needed. Surgery was performed under aseptic condi- bic structures to prefrontal cortices are, to some extent, region- tions. The monkey’s head was firmly positioned in a holder which ally specific. Thus, although the amygdala primarily targets the left the cranium unobstructed for surgical approach.
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