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Menno P Witter - One of the best experts on this subject based on the ideXlab platform.
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the entorhinal cortex of the monkey vi organization of projections from the hippocampus subiculum presubiculum and Parasubiculum
The Journal of Comparative Neurology, 2021Co-Authors: Menno P Witter, David G AmaralAbstract:The organization of projections from the macaque monkey hippocampus, subiculum, presubiculum, and Parasubiculum to the entorhinal cortex was analyzed using anterograde and retrograde tracing techniques. Projections exclusively originate in the CA1 field of the hippocampus and in the subiculum, presubiculum, and Parasubiculum. The CA1 and subicular projections terminate most densely in Layers V and VI of the entorhinal cortex, with sparser innervation of the deep portion of Layers III and II. Entorhinal projections from CA1 and the subiculum are topographically organized such that a rostrocaudal axis of origin is related to a medial-to-lateral axis of termination. A proximodistal axis of origin in CA1 and distoproximal axis in subiculum are related to a rostrocaudal axis of termination in the entorhinal cortex. The presubiculum sends a dense, bilateral projection to caudal parts of the entorhinal cortex. This projection terminates most densely in Layer III with sparser termination in Layers I, II, and V. The same parts of entorhinal cortex receive a dense projection from the Parasubiculum. This projection terminates in Layers III and II. Both presubicular and parasubicular projections demonstrate the same longitudinal topographic organization as the projections from CA1 and the subiculum. These studies demonstrate that: (a) hippocampal and subicular inputs to the entorhinal cortex in the monkey are organized similar to those described in nonprimate species; (b) the topographic organization of the projections from the hippocampus and subicular areas matches that of the reciprocal projections from the entorhinal cortex to the hippocampus and the subicular areas.
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topographic organization of orbitofrontal projections to the parahippocampal region in rats
The Journal of Comparative Neurology, 2014Co-Authors: Hideki Kondo, Menno P WitterAbstract:The parahippocampal region, which comprises the perirhinal, postrhinal, and entorhinal cortices, as well as the pre- and Parasubiculum, receives inputs from several association cortices and provides the major cortical input to the hippocampus. This study examined the topographic organization of projections from the orbitofrontal cortex (OFC) to the parahippocampal region in rats by injecting anterograde tracers, biotinylated dextran amine (BDA) and Phaseolus vulgaris-leucoagglutinin (PHA-L), into four subdivisions of OFC. The rostral portion of the perirhinal cortex receives strong projections from the medial (MO), ventral (VO), and ventrolateral (VLO) orbitofrontal areas and the caudal portion of lateral orbitofrontal area (LO). These projections terminate in the dorsal bank and fundus of the rhinal sulcus. In contrast, the postrhinal cortex receives a strong projection specifically from VO. All four subdivisions of OFC give rise to projections to the dorsolateral parts of the lateral entorhinal cortex (LEC), preferentially distributing to more caudal levels of LEC. The medial entorhinal cortex (MEC) receives moderate input from VO and weak projections from MO, VLO, and LO. The presubiculum receives strong projections from caudal VO but only weak projections from other OFC regions. As for the laminar distribution of projections, axons originating from OFC terminate more densely in upper layers (layers I-III) than in deep layers in the parahippocampal region. These results thus show a striking topographic organization of OFC-to-parahippocampal connectivity. Whereas LO, VLO, VO, and MO interact with perirhinal-LEC circuits, the interactions with postrhinal cortex, presubiculum, and MEC are mediated predominantly through the projections of VO.
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Progressive spread of tauopathy in NT mice identified by antibody MC1.
2013Co-Authors: Li Liu, Menno P Witter, Valerie Drouet, Scott A. Small, Catherine Clelland, Karen DuffAbstract:Fig. 2A shows tau immunolabeled with the human tau specific, conformational antibody MC1 in a young NT mouse at low power, and higher power (Figs. 2D, G). Fig. 2B shows MC1 immunolabeling in an old NT mouse at low power, and higher power (Figs. 2E, H). Fig. 2F shows high power image of cells immunolabeled with MC1 within the MEC. Old NT mice show extensive accumulation of human tau in cell bodies in the EC and subiculum (Fig. 2H), and in synaptically connected areas in the hippocampus and neocortex (Fig. 2E). Fig. 2I shows accumulation of human tau in neurons of the perirhinal cortex and into the parietal region in the old NT mouse. Note the lack of neurite staining in the perirhinal cortex compared to the LEC. Fig. 2C shows lack of immunolabeling with the human specific antibody in an old, littermate control mouse (single transgenic tau responder mouse, no tTA) except for the non-specific staining of the fornix that was seen with all antibodies. MEC = medial entorinal cortex, LEC = lateral entorhinal cortex, Pe = perirhinal cortex, Par = parietal cortex, DG = dentate gyrus, CA1, CA3 = CA fields of hippocampus, Su = subiculum, Prp-PaS = pre-Parasubiculum, pp = perforant pathway endzone. Figs. 2A–C magnification = 2×, Figs. 2D, E magnification = 4×, Figs. 2G–I magnification = 10×. Fig. 2F magnification = 40×.
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cingulate cortex projections to the parahippocampal region and hippocampal formation in the rat
Hippocampus, 2007Co-Authors: Bethany F Jones, Menno P WitterAbstract: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.
David G Amaral - One of the best experts on this subject based on the ideXlab platform.
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the entorhinal cortex of the monkey vi organization of projections from the hippocampus subiculum presubiculum and Parasubiculum
The Journal of Comparative Neurology, 2021Co-Authors: Menno P Witter, David G AmaralAbstract:The organization of projections from the macaque monkey hippocampus, subiculum, presubiculum, and Parasubiculum to the entorhinal cortex was analyzed using anterograde and retrograde tracing techniques. Projections exclusively originate in the CA1 field of the hippocampus and in the subiculum, presubiculum, and Parasubiculum. The CA1 and subicular projections terminate most densely in Layers V and VI of the entorhinal cortex, with sparser innervation of the deep portion of Layers III and II. Entorhinal projections from CA1 and the subiculum are topographically organized such that a rostrocaudal axis of origin is related to a medial-to-lateral axis of termination. A proximodistal axis of origin in CA1 and distoproximal axis in subiculum are related to a rostrocaudal axis of termination in the entorhinal cortex. The presubiculum sends a dense, bilateral projection to caudal parts of the entorhinal cortex. This projection terminates most densely in Layer III with sparser termination in Layers I, II, and V. The same parts of entorhinal cortex receive a dense projection from the Parasubiculum. This projection terminates in Layers III and II. Both presubicular and parasubicular projections demonstrate the same longitudinal topographic organization as the projections from CA1 and the subiculum. These studies demonstrate that: (a) hippocampal and subicular inputs to the entorhinal cortex in the monkey are organized similar to those described in nonprimate species; (b) the topographic organization of the projections from the hippocampus and subicular areas matches that of the reciprocal projections from the entorhinal cortex to the hippocampus and the subicular areas.
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macaque monkey retrosplenial cortex ii cortical afferents
The Journal of Comparative Neurology, 2003Co-Authors: Yasushi Kobayashi, David G AmaralAbstract:We investigated the cortical afferents of the retrosplenial cortex and the adjacent posterior cingulate cortex (area 23) in the macaque monkey by using the retrograde tracers Fast blue and Diamidino yellow. We quantitatively analyzed the distribution of labeled neurons throughout the cortical mantle. Injections involving the retrosplenial cortex resulted in labeled neurons within the retrosplenial cortex and in areas 23 and 31 (∼78% of the total labeled cells). In the remainder of the cortex, the heaviest projections originated in the hippocampal formation, including the entorhinal cortex, subiculum, presubiculum, and Parasubiculum. The parahippocampal and perirhinal cortices also contained many labeled neurons, as did the prefrontal cortex, mainly in areas 46, 9, 10, and 11, and the occipital cortex, mainly area V2. Injections in area 23 also resulted in numerous labeled cells in the posterior cingulate and retrosplenial regions (∼67% of total labeled cells). As in the retrosplenial cortex, injections of area 23 led to many labeled neurons in the frontal cortex, although most of these cells were in areas 9 and 46. Larger numbers of retrogradely labeled cells were also distributed more widely in the posterior parietal cortex, including areas 7a, 7m, LIP, and DP. There were some labeled cells in the parahippocampal cortex. These connections are consistent with the retrosplenial cortex acting as an interface between the working memory functions in the prefrontal areas and the long-term memory encoding in the medial temporal lobe. The posterior cingulate cortex, in contrast, may be more highly associated with visuospatial functions. J. Comp. Neurol. 466:48–79, 2003. © 2003 Wiley-Liss, Inc.
Michael Brecht - One of the best experts on this subject based on the ideXlab platform.
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Home, head direction stability and grid cell distortion
Cold Spring Harbor Laboratory, 2019Co-Authors: Juan Ignacio Sanguinetti-scheck, Michael BrechtAbstract:AbstractThe home is a unique location in the life of humans and animals. Numerous behavioral studies investigating homing indicate that many animals maintain an online representation of the direction of the home, a home vector. Here we placed the rat’s home cage in the arena, while recording neurons in the animal’s Parasubiculum and medial entorhinal cortex. From a pellet hoarding paradigm it became evident that the home cage induced locomotion patterns characteristic of homing behaviors. We did not observe home-vector cells. We found that head-direction signals were unaffected by home location. However, grid cells were distorted in the presence of the home cage. While they did not globally remap, single firing fields were translocated towards the home. These effects appeared to be geometrical in nature rather than a home-specific distortion. Our work suggests that medial entorhinal cortex and Parasubiculum do not contain an explicit neural representation of the home direction.
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Complementary Modular Microcircuits of the Rat Medial Entorhinal Cortex
Frontiers in Systems Neuroscience, 2017Co-Authors: Saikat Ray, Michael Brecht, Andrea Burgalossi, Robert K. NaumannAbstract:The parahippocampal region is organized into different areas, with the medial entorhinal cortex, presubiculum and Parasubiculum prominent in spatial memory. Here we also describe a region at the extremity at of the medial entorhinal cortex and bordering the subicular complex, the medial-most part of the entorhinal cortex. While the subdivisions of hippocampus proper form more or less continuous cell sheets, the superficial layers of the parahippocampal region have a distinct modular architecture. We investigate the spatial distribution, laminar position, and putative connectivity of zinc-positive modules in layer 2 of the medial entorhinal cortex of rats and relate them to the calbindin-positive patches previously described in the entorhinal cortex. We found that the zinc-positive modules are complementary to the previously described calbindin-positive patches. We also found that inputs from the presubiculum are directed towards the zinc-positive modules while the calbindin-positive patches received inputs from the Parasubiculum. Notably, the dendrites of neurons from layers 3 and 5, positive for Purkinje Cell Protein 4 expression, overlap with the zinc modules. Our data thus indicate that these two complementary modular systems, the calbindin patches and zinc modules, are part of parallel information streams in the hippocampal formation.
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cell type specific differences in spike timing and spike shape in the rat Parasubiculum and superficial medial entorhinal cortex
Cell Reports, 2016Co-Authors: Christian Laut Ebbesen, Saikat Ray, Andrea Burgalossi, Qiusong Tang, Eric T Reifenstein, Susanne Schreiber, Richard Kempter, Michael BrechtAbstract:The medial entorhinal cortex (MEC) and the adjacent Parasubiculum are known for their elaborate spatial discharges (grid cells, border cells, etc.) and the precessing of spikes relative to the local field potential. We know little, however, about how spatio-temporal firing patterns map onto cell types. We find that cell type is a major determinant of spatio-temporal discharge properties. Parasubicular neurons and MEC layer 2 (L2) pyramids have shorter spikes, discharge spikes in bursts, and are theta-modulated (rhythmic, locking, skipping), but spikes phase-precess only weakly. MEC L2 stellates and layer 3 (L3) neurons have longer spikes, do not discharge in bursts, and are weakly theta-modulated (non-rhythmic, weakly locking, rarely skipping), but spikes steeply phase-precess. The similarities between MEC L3 neurons and MEC L2 stellates on one hand and parasubicular neurons and MEC L2 pyramids on the other hand suggest two distinct streams of temporal coding in the parahippocampal cortex.
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Grid-Layout and Theta-Modulation of Layer 2 Pyramidal Neurons in Medial Entorhinal Cortex
Science, 2014Co-Authors: Saikat Ray, Helene Schmidt, Andrea Burgalossi, Robert K. Naumann, Qiusong Tang, Michael BrechtAbstract:Little is known about how microcircuits are organized in layer 2 of the medial entorhinal cortex. We visualized principal cell microcircuits and determined cellular theta-rhythmicity in freely moving rats. Non–dentate-projecting, calbindin-positive pyramidal cells bundled dendrites together and formed patches arranged in a hexagonal grid aligned to layer 1 axons, Parasubiculum, and cholinergic inputs. Calbindin-negative, dentate-gyrus–projecting stellate cells were distributed across layer 2 but avoided centers of calbindin-positive patches. Cholinergic drive sustained theta-rhythmicity, which was twofold stronger in pyramidal than in stellate neurons. Theta-rhythmicity was cell-type–specific but not distributed as expected from cell-intrinsic properties. Layer 2 divides into a weakly theta-locked stellate cell lattice and spatiotemporally highly organized pyramidal grid. It needs to be assessed how these two distinct principal cell networks contribute to grid cell activity.
Toshio Iijima - One of the best experts on this subject based on the ideXlab platform.
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Parahippocampal and retrosplenial connections of rat posterior parietal cortex.
Hippocampus, 2017Co-Authors: Grethe M. Olsen, Shinya Ohara, Toshio IijimaAbstract:The posterior parietal cortex has been implicated in spatial functions, including navigation. The hippocampal and parahippocampal region and the retrosplenial cortex are crucially involved in navigational processes and connections between the parahippocampal/retrosplenial domain and the posterior parietal cortex have been described. However, an integrated account of the organization of these connections is lacking. Here, we investigated parahippocampal connections of each posterior parietal subdivision and the neighboring secondary visual cortex using conventional retrograde and anterograde tracers as well as transsynaptic retrograde tracing with a modified rabies virus. The results show that posterior parietal as well as secondary visual cortex entertain overall sparse connections with the parahippocampal region but not with the hippocampal formation. The medial and lateral dorsal subdivisions of posterior parietal cortex receive sparse input from deep layers of all parahippocampal areas. Conversely, all posterior parietal subdivisions project moderately to dorsal presubiculum, whereas rostral perirhinal cortex, postrhinal cortex, caudal entorhinal cortex and Parasubiculum all receive sparse posterior parietal input. This indicated that the presubiculum might be a major liaison between parietal and parahippocampal domains. In view of the close association of the presubiculum with the retrosplenial cortex, we included the latter in our analysis. Our data indicate that posterior parietal cortex is moderately connected with the retrosplenial cortex, particularly with rostral area 30. The relative sparseness of the connectivity with the parahippocampal and retrosplenial domains suggests that posterior parietal cortex is only a modest actor in forming spatial representations underlying navigation and spatial memory in parahippocampal and retrosplenial cortex. © 2017 Wiley Periodicals, Inc.
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Distribution of retrogradely labeled neurons three days after virus injections into dorsal DG.
2013Co-Authors: Shinya Ohara, Sho Sato, Ken-ichiro Tsutsui, Toshio IijimaAbstract:Series of coronal sections (organized from rostral to caudal) for a rat surviving three days after dorsal DG injection. APC, anterior piriform cortex; APir, amygdalopiriform transition; AUD, auditory cortex; BaA, basal complex of amygdala; CeA, central amygdaloid nucleus; Cg, cingulate cortex; Cl, claustrum; CoA, cortical amygdaloid nucleus; CPu, caudate putamen; DB, diagonal band; DMH, dorsomedial hypothalamic nucleus; DP, dorsal peduncular cortex; En, endopiriform nucleus; EC, entorhinal cortex; IL, infralimbic cortex; Ins, insular cortex; IP, interpedunclular nucleus; LaA, lateral amygdaloid nucleus; LS, lateral septum; MeA, medial amygdaloid nucleus; mHb, medial habenular nucleus; mRn, median raphe nucleus; MO, motor cortex; MS, medial septum; MTu, medial tuberal nucleus; PAG, periaqueductal gray; PaS, Parasubiculum; PER, perirhinal cortex; PL, prelimbic cortex; POR, postrhinal cortex; PPC, posterior piriform cortex; PrS, presubiculum; PtA, parietal association cortex; RSC, retrosplenial cortex; SS, somatosensory cortex; Sub, subiculum; SuM, supramammillary nucleus; TeA, temporal association cortex; TT, tenia tecta; VIS, visual cortex; VMH, ventromedial hypothalamic nucleus.
Shinya Ohara - One of the best experts on this subject based on the ideXlab platform.
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architecture of the entorhinal cortex a review of entorhinal anatomy in rodents with some comparative notes
Frontiers in Systems Neuroscience, 2017Co-Authors: Thanh P. Doan, Bente Jacobsen, Eirik Stamland Nilssen, Shinya OharaAbstract:The entorhinal cortex (EC) is the major input and output structure of the hippocampal formation, forming the nodal point in cortico-hippocampal circuits. Different division schemes including two or many more subdivisions have been proposed, but here we will argue that subdividing EC into two components, the lateral (LEC) and medial EC (MEC) might suffice to describe the functional architecture of EC. This subdivision then leads to an anatomical interpretation of the different phenotypes of LEC and MEC. First, we will briefly summarize the cytoarchitectonic differences and differences in hippocampal projection patterns on which the subdivision between LEC and MEC traditionally is based and provide a short comparative perspective. Second, we focus on main differences in cortical connectivity, leading to the conclusion that the apparent differences may well correlate with the functional differences. Cortical connectivity of MEC is features interactions with areas such as the presubiculum, Parasubiculum, retrosplenial cortex and postrhinal cortex, all areas that are considered to belong to the ’spatial processing domain’ of the cortex. In contrast, LEC is strongly connected with olfactory areas, insular, medial- and orbitofrontal areas and perirhinal cortex. These areas are likely more involved in processing of object information, attention and motivation. Third, we will compare the intrinsic networks involving principal- and inter-neurons in LEC and MEC. Together, these observations suggest that the different phenotypes of both EC subdivisions likely depend on the combination of intrinsic organization and specific sets of inputs. We further suggest a reappraisal of the notion of EC as a layered input-output structure for the hippocampal formation.
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Parahippocampal and retrosplenial connections of rat posterior parietal cortex.
Hippocampus, 2017Co-Authors: Grethe M. Olsen, Shinya Ohara, Toshio IijimaAbstract:The posterior parietal cortex has been implicated in spatial functions, including navigation. The hippocampal and parahippocampal region and the retrosplenial cortex are crucially involved in navigational processes and connections between the parahippocampal/retrosplenial domain and the posterior parietal cortex have been described. However, an integrated account of the organization of these connections is lacking. Here, we investigated parahippocampal connections of each posterior parietal subdivision and the neighboring secondary visual cortex using conventional retrograde and anterograde tracers as well as transsynaptic retrograde tracing with a modified rabies virus. The results show that posterior parietal as well as secondary visual cortex entertain overall sparse connections with the parahippocampal region but not with the hippocampal formation. The medial and lateral dorsal subdivisions of posterior parietal cortex receive sparse input from deep layers of all parahippocampal areas. Conversely, all posterior parietal subdivisions project moderately to dorsal presubiculum, whereas rostral perirhinal cortex, postrhinal cortex, caudal entorhinal cortex and Parasubiculum all receive sparse posterior parietal input. This indicated that the presubiculum might be a major liaison between parietal and parahippocampal domains. In view of the close association of the presubiculum with the retrosplenial cortex, we included the latter in our analysis. Our data indicate that posterior parietal cortex is moderately connected with the retrosplenial cortex, particularly with rostral area 30. The relative sparseness of the connectivity with the parahippocampal and retrosplenial domains suggests that posterior parietal cortex is only a modest actor in forming spatial representations underlying navigation and spatial memory in parahippocampal and retrosplenial cortex. © 2017 Wiley Periodicals, Inc.
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Architecture of the Entorhinal Cortex A Review of Entorhinal Anatomy in Rodents with Some Comparative Notes
Frontiers Media S.A., 2017Co-Authors: Thanh P. Doan, Bente Jacobsen, Eirik Stamland Nilssen, Shinya OharaAbstract:The entorhinal cortex (EC) is the major input and output structure of the hippocampal formation, forming the nodal point in cortico-hippocampal circuits. Different division schemes including two or many more subdivisions have been proposed, but here we will argue that subdividing EC into two components, the lateral EC (LEC) and medial EC (MEC) might suffice to describe the functional architecture of EC. This subdivision then leads to an anatomical interpretation of the different phenotypes of LEC and MEC. First, we will briefly summarize the cytoarchitectonic differences and differences in hippocampal projection patterns on which the subdivision between LEC and MEC traditionally is based and provide a short comparative perspective. Second, we focus on main differences in cortical connectivity, leading to the conclusion that the apparent differences may well correlate with the functional differences. Cortical connectivity of MEC is features interactions with areas such as the presubiculum, Parasubiculum, retrosplenial cortex (RSC) and postrhinal cortex, all areas that are considered to belong to the “spatial processing domain” of the cortex. In contrast, LEC is strongly connected with olfactory areas, insular, medial- and orbitofrontal areas and perirhinal cortex. These areas are likely more involved in processing of object information, attention and motivation. Third, we will compare the intrinsic networks involving principal- and inter-neurons in LEC and MEC. Together, these observations suggest that the different phenotypes of both EC subdivisions likely depend on the combination of intrinsic organization and specific sets of inputs. We further suggest a reappraisal of the notion of EC as a layered input-output structure for the hippocampal formation
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Distribution of retrogradely labeled neurons three days after virus injections into dorsal DG.
2013Co-Authors: Shinya Ohara, Sho Sato, Ken-ichiro Tsutsui, Toshio IijimaAbstract:Series of coronal sections (organized from rostral to caudal) for a rat surviving three days after dorsal DG injection. APC, anterior piriform cortex; APir, amygdalopiriform transition; AUD, auditory cortex; BaA, basal complex of amygdala; CeA, central amygdaloid nucleus; Cg, cingulate cortex; Cl, claustrum; CoA, cortical amygdaloid nucleus; CPu, caudate putamen; DB, diagonal band; DMH, dorsomedial hypothalamic nucleus; DP, dorsal peduncular cortex; En, endopiriform nucleus; EC, entorhinal cortex; IL, infralimbic cortex; Ins, insular cortex; IP, interpedunclular nucleus; LaA, lateral amygdaloid nucleus; LS, lateral septum; MeA, medial amygdaloid nucleus; mHb, medial habenular nucleus; mRn, median raphe nucleus; MO, motor cortex; MS, medial septum; MTu, medial tuberal nucleus; PAG, periaqueductal gray; PaS, Parasubiculum; PER, perirhinal cortex; PL, prelimbic cortex; POR, postrhinal cortex; PPC, posterior piriform cortex; PrS, presubiculum; PtA, parietal association cortex; RSC, retrosplenial cortex; SS, somatosensory cortex; Sub, subiculum; SuM, supramammillary nucleus; TeA, temporal association cortex; TT, tenia tecta; VIS, visual cortex; VMH, ventromedial hypothalamic nucleus.
