Organization of Corticocortical Connections in the Parietal Cortex of the Rat REBECCA M. AKERS AND HERBERT P.KILLACKEY Department of Psychobiology, University of California, Irvine, California 9271 7

ABSTRACT An analysis based on Nissl, anterograde degeneration, and succinic dehydrogenase histochemical techniques reveals that there are two distinct regions of parietal cortex which are characterized by different cytoarchitectonic features and anatomical connections. The “granular” cortical zone possesses a well-defined fourth layer composed of small, densely-packed cells, receives dense projections from the ventral posterior nucleus of the thalamus, and is essentially free of callosal inputs. “Agranular” cortical areas which surround or lie embedded within the granular zone lack a well-defined fourth layer, receive sparse projection from the ventral posterior nucleus, but send and receive extensive callosal projections. These findings suggest that thalamic and callosal projections to the parietal cortex maintain a pattern of areal segregation. The granular cortical zone, which apparently corresponds to SmI, projects ipsilaterally t o motor cortex, SmII, and adjacent agranular areas. The superficial layers of the granular cortex also project heavily upon the underlying layer V. This intracortical projection is not organized in discrete clusters within the “barrel field” cortex. This suggests that the specialized organization of thalamic afferents and granule cells within the “barrel field” is not maintained in the intracortical circuitry of this region. The heterogeneous distribution of interhemispheric connections within the cerebral cortex has been demonstrated in a number of mammalian species. It is now generally recognized that different regions of the cortex vary considerably in the density of the commissural projections they send and receive. For example, in the opossum (Ebner, ’67), cat (Ebner and Myers, ’65; Jones and Powell, ’68a1, racoon (Ebner and Myers, ‘651,and monkey (Jones and Powell, ’69b; Karol and Pandya, ’71) zones of somatosensory cortex associated with distal limb regions are virtually devoid of commissural input. Likewise, in the cat (Hubel and Wiesel, ’67) and monkey (Ebner and Myers, ‘62;Wilson, ’62),the interhemispheric connections of the visual cortex (area 17) are limited to the zone representing the vertical meridian. This heterogeneous distribution of callosal projections has been interpreted in various ways. It has been suggested that regions of sensory cortex representing axial structures andlor receiving bilateral inputs are preferentially connected by interhemispheric projections, while distal or lateral sensory fields are acallosal (Jones and J. COMP. NEUR. 11978) 181: 513-538.

Powell, ’68a,b, ’73; Karol and Pandya, ’71; Pandya and Vignolo, ’69; Wise and Jones, ’76). A similar organization has been suggested for the callosal projections of the motor cortex (Pandya et al., ’69).An alternative interpretation is that regions of sensory cortex specialized for the “reception of specific thalamic projections” lack appreciable interhemispheric connections (Ebner, ’67). If the latter interpretation is correct, it is expected that areas of sensory cortex associated with highly developed peripheral receptor organs would receive sparse commissural projections. In many sensory systems these two interpretations are consistent. In the racoon (Ebner and Myers, ’65) and monkey (Jones and Powell, ’69b), the distal forelimb region of the somatosensory cortex is highly developed and receives sparse connections across the midline. However, in the rat, mouse, and certain other rodents these two interpretations are not consistent. In these animals portions of somatosensory cortex associated with the mystacial vibrissae and sinus hairs are char-

‘ Research supported by NSF Grant GB 41294. Supported by NSF Predoctoral Fellowship.

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acterized by an elaborate cytoarchitectonic specialization. Within layer IV discrete clusters of cells, termed “barrels,” are related to individual facial hairs (Woolsey and van der Loos, ‘70; Welker and Woolsey, ‘74; Woolsey et al., ’75) and receive equally discrete clusters of thalamocortical projections (Killackey, ‘73; Killackey and Leshin, ’75; Donaldson et al., ’75). Thus, the “barrel field” cortex represents an axial body region, but is highly specialized both in its internal organization and in the thalamic projections i t receives. It is of interest, therefore, to determine whether this region is the recipient of a major callosal input. In addition, the discrete organization of the thalamic afferents to the “barrel field” suggests the possibility that the efferent connections of this area may be organized in a similar clustered fashion. With these questions in mind, we have undertaken an investigation of the ipsilateral and contralateral corticocortical connections of the parietal cortex of the rat. MATERIALS AND METHODS

Subjects were female Long-Evans agouti rats, ranging in age from 60 to 100 days. Three types of lesions were made. Complete section of the corpus callosum was carried out with the aid of an operating microscope. Following removal of a bone flap lying 1 mm lateral to the midline, the underlying strip of cortex and corpus callosum were aspirated. This procedure usually involved damage to the septum and hippocampus, and observation in these cases was limited t o the contralateral hemisphere. Small electrolytic lesions of parietal cortex were also made. In these cases a small hole was drilled in the skull, and a stainless steel microelectrode was lowered into the cortex with the aid of a micromanipulator. Lesions were made at varying depths within the cortex, but were divided for analysis into two classes: those damaging only the superficial cortical layers (I-III),and those involving the underlying infragranular layers (V and VI) as well. These lesions ranged in diameter from 200- 1,000 pm. Large electrolytic lesions were also made in the ventral posterior nucleus of the thalamus. Such lesions were made from a posterior horizontal approach in order to avoid neocortical damage and were used to compare the distribution of thalamic and corticocortical afferents. Survival times varied from four to nine days postlesion. Subjects received an overdose of

sodium pentobarbitol and were perfused with physiological saline followed by 10%formalin. Brains were stored in 10% formalin for one week and transferred to a 30%sucroselformalin solution for an additional three days. They were sectioned at 40 pm on a freezing microtome and processed according to the FinkHeimer technique I (Fink and Heimer, ’67). Alternate sections were stained with cresyl violet. In addition, several unlesioned subjects were sacrificed and perfused with 10%glycerol for use in a succinic dehydrogenase histochemical stain. Slabs of parietal cortex were dissected, flattened according to the procedure described by Welker and Woolsey (’741, and sectioned at 30 pm on a cryostatic microtome. Sections were incubated a t 37°C for one hour in a solution containing sodium succinate (50 mM), nitrobluetetrazolium (55 pM) and phosphate buffer (50 mM). Terminal degeneration and cytoarchitectonic landmarks were plotted on drawings of coronal sections (magnified 14 times). From these coronal sections data were reconstructed on cortical topography maps projected a t a 45’ angle from the midsagittal plane. This procedure produced maximal accuracy of reconstruction in the zone of cortex displaying the greatest medial-to-lateral curvature (approximately the middle of the vibrissal representation). RESULTS

Callosal connections Aspiration of the corpus callosum produces a complex pattern of degeneration in the undamaged hemisphere. Terminal degeneration is not uniformly distributed within the contralateral cortical areas, but is marked instead by sharp laminar and regional discontinuities. Such discontinuities are visualized best in coronal sections (fig. 1A). Terminal degeneration is moderate to heavy in areas of parietal cortex lying medial to the longitudiFig. 1 Drawings of coronal sections taken from approximately equivalent areaa of parietal cortex. A, FinkHeimer preparation following transection of the corpus callosum; B, Nisal stain; C, Fink-Heimer preparation following a large lesion of the ventral posterior nucleus of the thalamus. Note the correspondence between the zone of sparse callosal input and that receiving dense thalamic projections (A and C). Arrows indicate narrow strips of callosal recipient cortex embedded within the acallosal zone. Acallosal and callosal recipient areas of cortex are characterized by different morphological features, as illustrated in Nissl preparations (B).

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nal fissure (fig. 1A [I1 and just dorsal to the rhinal fissure (fig. 1A [21). In these zones, degenerating fibers pass obliquely from the white matter, run tangentially for varying distances deep within layer VI, and turn to ascend vertically to terminal fields in more superficial cortical layers. Terminal degeneration is heaviest in layers 111, 11, and the inner one-half of layer I. Much sparser degeneration is seen within layers V and VI, and layer IV is virtually devoid of degenerating terminals. The two cortical areas just described enclose a third cortical zone which is essentially free of degenerating debris (fig. 1A [31). The border between this “acallosal” cortex and the surrounding callosal recipient zones is quite sharp, being more clearly defined medially than laterally. In addition, the acallosal zone is punctuated at intervals by narrow strips of cortex, approximately 250 pm wide, which contain dense terminal degeneration (indicated by arrow in fig. 1A and in fig. 8A). In these regions degenerating fibers form compact bundles within the deeper cortical layers and pass vertically through layer IV to terminate superficially in layers I, 11, and 111. Within the superficial layers, the degenerating fibers “fan out” to form a dense funnel-shaped terminal field. Terminal degeneration is sparser in layers V and VI and virtually absent in layer IV. Within these narrow callosal recipient zones, the horizontal spread of degenerating elements is much more restricted in layer IV than it is in the adjacent supragranular and infragranular layers. Comparison of Fink-Heimer stained sections with Nissl material suggests that the borders between callosal recipient and acallosal cortical zones correspond to well-defined cytoarchitectonic boundaries. In Nissl-stained sections, the acallosal zone is characterized by a sharply-defined fourth cortical layer composed of densely-packed granule cells. The subjacent layer Va is pale and cell sparse (fig. 1B). These same cytoarchitectonic features characterize the region of cortex defined electrophysiologically as SmI (Welker, ’71, ’76). A different pattern of cytoarchitectonic organization characterizes the callosal recipient cortex which surrounds and lies embedded within the acallosal zone. Areas of parietal cortex which receive dense callosal projections appear poorly-laminated in Nissl-stained sections. The density of cells within the fourth cortical layer is much reduced in comparison with adjacent, granular cortical areas. Indeed,

in callosal recipient zones the density of cells seems relatively uniform across layers I1 through VI (figs. lB, 8B). The apparent correspondence between the distribution of the callosal afferents and the cytoarchitectonic features which distinguish somatosensory cortex led us t o examine more closely the distribution of the thalamic afferents to this region. Following large lesions of the ventral posterior nucleus, dense fiber and terminal degeneration is found throughout the major portion of the parietal cortex (fig. 2 0 . Coarse, degenerating fibers enter the subcortical white matter from the internal capsule and ascend to terminate densely within the fourth cortical layer. The distribution of degenerating terminals within this thalamic field corresponds quite closely to the boundaries of the granular cortical area. In coronal sections (fig. 1C) the density of degenerating terminals falls off sharply a t the medial and lateral borders of the well-defined fourth cortical layer. In addition, the band of dense terminal degeneration within the layer IV is interrupted a t intervals by narrow zones in which the terminal density is much reduced (fig. 8C). These narrow zones correspond to the callosal recipient strips of cortex and are likewise characterized by a reduction in the density of granule cells within the fourth cortical layer. In order to rule out the possibility that these interruptions in the thalamic terminal field were due to incomplete lesions of the ventral posterior nucleus, we also examined the distribution of thalamic afferents with the succinic dehydrogenase histochemical stain (SDH). This oxidative enzyme is localized within the mitochondria (Friede, ‘66) and is distributed in the somatosensory cortex in a pattern which closely resembles the distribution of the thalamic afferents (Friede, ’60; Labedsky and Lierse, ’68; Killackey et al., ”76). Thus, it appears that the SDH stain reveals the pattern of thalamic projections by staining dense concentrations of mitochondria within the synaptic terminals in layer IV. In coronal SDH sections, the medial and lateral boundaries of the thalamic recipient zone are clearly visible (fig. 9). In addition, discontinuities in the darkly-staining fourth cortical layer are also apparent. In flattened tangential sections, discontinuities in the thalamic projection are even more evident. A comparison of figure 10 with flattened Nissl preparations shown by Welker (’76) suggests that the distribution of the thalamic afferents

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closely corresponds to the pattern of granule cell aggregates within the parietal cortex. Lesions of the ventral posterior nucleus of the thalamus also produce terminal degeneration which lies outside the granular area of parietal cortex. This second terminal field lies posterior and ventral to the “barrel field” region approximately 1 mm above the rhinal fissure. Comparison of our data with the electrophysiological map of Welker and Sinha (’72) suggests that this projection site corresponds to the SmII cortical region. Following callosal transection, this same area is the site of moderate fiber and terminal degeneration. As elsewhere in the parietal cortex, the callosal terminal field in SmII is localized primarily within the upper three layers and, to a lesser extent, in layers V and VI. The results of combined cytoarchitectonic, lesion, and histochemical data are presented in figure 2 and in figures 8A, B, and C. In figure 2 the total pattern of callosal afferents, the distribution of the well-defined granule cell layer, and the pattern of thalamocortical projections as revealed by the Fink-Heimer and SDH techniques are projected onto 45’ cortical maps. These data suggest that the “acallosal” zone of parietal cortex coincides to a large extent with the cortical area characterized by a well-defined layer of denselypacked granule cells. This same region receives a dense projection from the ventral posterior nucleus of the thalamus, while agranular cortical zones surrounding and embedded within the granular cortex receive much sparser thalamic projections. Within the second projection site of the ventral posterior thalamus (SmII), thalamic and callosal projections converge on the same cortical area. Ipsilateral connections Lesions involving infragranular cortical layers Small electrolytic lesions placed within the parietal cortex produce several foci of terminal degeneration in the ipsilateral hemisphere. Figure 3 depicts the pattern of degeneration seen after a lesion which is confined to the granular posterior “barrel field” and involves layers I-V. Fine, densely packed terminal degeneration surrounds the lesion site. Within the superficial layers, degenerating fibers and terminals extend some distance from the lesion, but this degeneration does not extend beyond the boundaries of the granular

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cortical area. Columns of degenerating fibers descend vertically from the lesion site and enter the underlying white matter. The greatest number of these enter the internal capsule

B

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D Fig. 2 Data obtained from coronal sections reconstructed onto cortical topography maps projected at a 45” angle from the midsagittal plane. A, stippling indicates areas of dense terminal degeneration as seen in FinkHeimer preparations following callosal transection. Light areas indicate zones where terminal degeneration is sparse or absent; B, area of parietal cortex characterized by a well-defined granule cell layer, 88 seen in Nissl preparations; C, distribution of terminal degeneration in FinkHeimer preparations following a large lesion of the ventral posterior nucleus of the thalamus; D, zone of dense thalamic input aa assessed by the succinic dehydrogenase histochemical technique.

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Fig. 3 Pattern of ipsilateral terminal degeneration resulting from a lesion of granular cortex involving layers I-V. Terminal fields indicated by number on the cortical topography map are also illustrated in drawings of coronal sections taken at different levels of parietal cortex (A, B, and C). Note projections to the second somatosensory area (l), motor cortex (2), and agranular zones adjacent to the lesion site (3, 4, and 5 ) .

enroute to subcortical sites. In addition, two major bundles travel within the white matter to terminate in other ipsilateral cortical areas. One bundle sweeps laterally, travels superficially within the white matter toward the rhinal fissure, and ascends vertically to a terminal field in the fourth cortical layer (fig. 3 Ill). This projection site is small, well-defined, and relatively constant in location from lesion-to-lesion. It lies lateral and posterior to the boundary of the granular cortical area. Lesions confined to the ventral posterior nucleus of the thalamus produce a terminal field within layer IV in this same region. It thus appears that this ipsilateral projection site corresponds to the second somatosensory area

(SmlI). Within this region projections from ipsilateral granular parietal areas and the ventral posterior thalamus converge on the same cortical layer. This convergence of inputs within layer IV is of particular interest since the other ipsilateral projections of the granular area are localized without exception in the three uppermost cortical layers. A second major group of fibers radiates medially from the lesion site and coalesces to form a compact bundle which travels within the superficial white matter and in the deepest portions of layer VI. This bundle courses medially, approaches the midline, and then passes rostrally to terminate in the superficial layers (1-111)of frontal cortex (fig. 3

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A Fig. 4 Pattern of ipsilateral terminal degeneration resulting from a lesion of the rostra1 portion of granular parietal cortex. A lesion of this type produces terminal fields in motor cortex (1) and in the agranular area lvina immediately adjacent to the rostromedial border of the granular zone (2). Other ipsilateral terminal fielde-(not illustraied)-resemble those in figure 5.

[21). This projection site lies within the region defined electrophysiologically as motor cortex (Hall and Lindholm, ’74).Since the majority of the cortical lesions in this study were concentrated within the “barrel field” region, it was not possible to determine whether this projection is organized in a topographical fashion. However, lesions of the “barrel field” cortex produce foci of degeneration in an area which appears to correspond to the region of vibrissae representation in motor cortex (see fig. 1of Hall and Lindholm, ’74). While the majority of the degenerating fibers which emanate from the lesion site enter the underlying white matter, fibers also pass directly through cortex to ipsilateral cortical areas. Fibers radiate tangentially from

the lesion, travel primarily within layer V, and terminate in the superficial layers of surrounding cortical zones. Three such projection sites are depicted in figures 3 [3,4and 51.The lateral projection (fig. 3 131) is the heaviest and lies just lateral to the border of the granular cortical region (figs. 11, 12).This projection is interposed between the boundary of the granular cortex and the more lateral projection to SmII. A second terminal field (fig. 3 [41) lies just medial and posterior to the boundary of the granular cortical area. Finally, a third terminal field (fig. 3 151) lies medial to the lesion and occurs within a prominent disruption in the granule cell layer. When lesions are placed more rostrally (fig. 4) a focus of terminal degeneration is seen on the

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t

t

\

Fig. 5 Pattern of ipsilateral terminal degeneration resulting from a lesion of granular cortex involving layers 1-111. Note the similarity between this pattern of terminal degeneration and that resulting from deeper lesions (fig. 3). A separate terminal field corresponding to 4 in figure 3 is not seen, apparently because the degeneration immediately surrounding the lesion site overlaps with this projection area.

anteromedial border of the granular cortical zone. These data suggest that the granular parietal cortex projects to a number of ipsilateral cortical sites which lie immediately adjacent to its cytoarchitectonic boundaries. These same regions also receive extensive callosal input. Thus, the granular parietal cortex is surrounded by a band of cortex which receives converging ipsilateral and contralateral corticocortical projections. Both sets of projections terminate primarily within the superficial layers. In the present study, we were unable to produce small lesions strictly confined to the narrow strips of agranular, callosal recipient cortex which lie embedded within the granular field. Hence, it was not possible to

explore the ipsilateral connections of these agranular cortical zones. Lesions involving supragranular layers Cortical lesions restricted to the supragranular layers (1-111) produce patterns of terminal degeneration which closely resemble those seen after deeper lesions (fig. 5 ) . This suggests that neither the ipsilateral nor the contralatera1 corticocortical projections arise solely from the infragranular layers. In addition to the terminal fields already described, lesions of the superficial cortical layers produce a heavy band of terminal degeneration within layer V immediately beneath the lesion site. This terminal field is of uniform density throughout (fig. 131, and there is no apparent

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Rg. 6 Patterns of terminal degeneration resulting from two different types of cortical lesions. A lesion (1) which encroaches upon agranular zones of parietal cortex produces contralateral foci of terminal degeneration in the same agranular zones (B). A lesion (2) confined to the granular parietal cortex produces no terminal degeneration in the contralateral hemisphere. Both types of lesions produce comparable patterns of ipsilateral terminal degeneration (A).

segregation of terminals into discrete units. This intracortical projection within the “barrel field” cortex is not organized in a fashion resembling the thalamocortical afferents to this region (Killackey, ’73; Killackey and Leshin, ’75).

Origin of the callosal projections from the parietal cortex Figure 6 illustrates the pattern of degeneration seen after two different electrolytic lesions of the parietal cortex. The lesion depicted in the upper right (1)produces fields of terminal degeneration in the ipsilateral (A) and contralateral (B) hemispheres. Enclosed within this lesion are two zones of reduced granule cell density. The terminal fields in the contralateral hemisphere are localized within the complementary agranular zones. In the lower right (2) a lesion is depicted which produces degeneration in the ipsilateral hemisphere only. This lesion is confined to the zone of cortex containing a well-defined granular layer. In all cases, lesions which do not encroach on areas of reduced granule cell density do not

produce terminal fields in the contralateral hemisphere. Lesions which do involve these agranular areas invariably result in contralateral foci of terminal degeneration. The pattern of ipsilateral degeneration is the same with both types of lesions. While it is possible that regions of the granular cortex not explored in this study may give rise to some callosal projections, i t appears that the bulk of the interhemispheric projections within parietal cortex both arise and terminate in zones of reduced granule cell density and sparse thalamic input. In particular, the “barrel field” region neither sends nor receives extensive callosal projections. DISCUSSION

Structural features of somatosensory cortex The term somatosensory cortex, as originally defined, refers to the portion of the neocortex which is responsive to somatic stimulation. This region has been delineated electrophysiologically in the rat by Woolsey and Lemessurier (’48) and, more recently, by Welker (‘71,’76). In the present experiment we

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have attempted to study the connections of this functionally defined cortical area using anatomical techniques. At this point it is relevant to consider the structural criteria which we have used to distinguish somatosensory cortex from surrounding areas of parietal cortex. Welker ('71) has reported that the cortical zone responsive to somatic stimulation in the rat is characterized by distinct cytoarchitectonic features: a well-defined fourth cortical layer composed of small, densely-packed granule cells, and a pale cell-sparse subjacent layer Va. More recently, she has found discontinuities within this granular cortical field (Welker, '76). Aggregates of granule cells related to individual body regions are separated by narrow zones of agranular cortex. Within these agranular zones, few single units can be isolated which are responsive to somatic stimulation. Welker has suggested that there is a correspondence between the aggregation of granule cells and the discontinuous mapping of the body on the cortical surface. Thus, the pattern of granule cell aggregates may form a true "rattunculus" within the parietal cortex. Our data likewise suggest the existence of discontinuities in the granule cell layer. Narrow, poorly-laminated zones of reduced granule cell density interrupt the granular cortical area; these same zones receive much sparser input from the ventral posterior nucleus of the thalamus than do surrounding granular zones. It thus appears that the region functionally defined as primary somatosensory cortex (SmI) corresponds closely to the granular cortical area which receives dense input from the ventral posterior thalamus. Patches of cortex surrounding the aggregates of granule cells are quite different both in their cytoarchitectonic characteristics and in the pattern of connections they receive. The corticocortical projections to these granular and agranular regions of parietal cortex will be discussed in detail below.

The areal distribution of corticocortical afferents The heterogeneous distribution of commissural afferents within the neocortex appears t o be a generalized mammalian feature. In virtually every species studied, large portions of occipital and parietal cortex lacking extensive interhemispheric connections have been described (Ebner and Myers, '62, '65;

Myers, '62; Ebner, '67; Wilson, '68; Jones and Powell, '68a, '69b; Hughes and Wilson, '69; Jacobson, '70; Heath and Jones, '71; Karol and Pandya, '71; Benevento and Ebner, '73; Yorke and Caviness, '75; Ryugo and Killackey, '75; Wise and Jones, '76). It has been suggested that these acallosal zones represent highly lateralized motor and sensory functions, while regions associated with axial or midline sensory fields receive dense commissural inputs (Jones and Powell, '68a, '69b, '73; Yorke and Caviness, '75; Wise and Jones, '76). It is therefore somewhat surprising that the major portion of the rat somatosensory cortex neither sends nor receives extensive commissural projections. Jacobson ('70) has previously reported the absence of callosal terminals within a large area of the rat parietal cortex and has proposed that this acallosal area corresponds to the distal limb representation. However, more recent reports have suggested that the zone receiving sparse callosal projections in both the rat (Ryugo and Killackey, '75; Wise and Jones, '76) and mouse (Yorke and Caviness, '75; White and DeAmicis, '77) includes the area of vibrissal representation. This finding is of particular interest since it has been reported that the head and face regions of the cat (Ebner and Myers, '65; Jones and Powell, '68a) and monkey (Jones and Powell, '69b; Karol and Pandya, '71) somatosensory cortex receive extensive commissural input. Yorke and Caviness ('75) have suggested that the mystacial vibrissae, like the distal limb regions, are highly lateralized sense organs. However, the present data suggest that the acallosal zone of the rat includes within it not only representations of lateralized sense organs, but regions representing the trunk and proximal limbs as well. This interpretation is based on the observation that the granular areas of parietal cortex are essentially devoid of callosal terminals. Since Welker ('76) has reported that the trunk and proximal limb regions of somatosensory cortex are granular, i t must be concluded that the acallosal zone includes the region of representation of these axial body structures. While the granular parietal cortex receives sparse callosal projections, narrow patches of agranular cortex intercalated between clusters of granule cells receive dense commissural input (Wise and Jones, '76). These callosal recipient zones in turn receive sparse projections from the ventral posterior nucleus

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of the thalamus. This suggests that the callosal and specific thalamocortical afferents terminate in non-overlapping areas of the rat parietal cortex. Such areal segregation of callosal and thalamic projections may exist in other species. For example, Ebner (‘69) has reported that patches of dense commissural input in the opossum neocortex are often localized in areas receiving sparse thalamic projections. Similarly, studies of callosal projections in the rhesus monkey have demonstrated the existence of discrete bands of commissural terminals similar to those in the rat parietal cortex, but the distribution of callosal and thalamic afferents has not been compared in detail (Jones e t al., ’75; Shanks et al., ’75; Kunzle, ’76; Goldman and Nauta, ’77). However, there is evidence which suggests that callosal recipient zones in the motor cortex of the rhesus monkey may receive sparse thalamic projections. Callosal projections to this region are organized in discrete “columns” similar to those seen in other species (Kunzle, ’76). The thalamic projection to motor cortex from the ventral lateral nucleus is interrupted by narrow “athalamic” regions which resemble those described in the present study (K. Kalil, personal communication), suggesting the possibility t h a t callosal and thalamic afferents may terminate in non-overlapping areas of motor cortex. While detailed comparison of the distribution of thalamic and callosal projections may reveal the existence of areal segregation in a number of cortical areas, such areal segregation is not a general rule, since there are regions of cortex which receive dense, overlapping projections from both thalamus and contralateral cortical areas. In the rat such areas include the primary auditory and peristriate cortices (D. Ryugo and Killackey, unpublished observations), as well as the second somatosensory area (SmII). The callosal projections to parietal cortex are apparently exclusively homotopic. Our data suggest that the agranular zones both send and receive the bulk of the callosal afferents. Previous data from the rat (Wise and Jones, ‘76) and mouse (Yorke and Caviness, ’75; White and DeAmicis, ’77) have likewise suggested t h a t the callosal projections arise from and terminate on homotopic groups of cortical cells. However, a heterotopic projection from SmI to the contralateral SmII area has been described in the rat (Wise and Jones,

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’76) and cat (Jones and Powell, ’69a; Morrison, ’671,a projection not detected in the present study. It is possible, however, that the smaller size of our cortical lesions precluded the demonstration of this commissural pathway. Although the granular parietal cortex is essentially acallosal, it projects to a number of ipsilateral areas which are extensively connected with points in the contralateral hemisphere. The ipsilateral motor cortex and SmII both receive inputs from granular parietal cortex, projections which have been described previously in the monkey (Jones and Powell, ’69a), cat (Jones and Powell, ’69b), and mouse (White and DeAmicis, ’77). In addition, discrete intracortical pathways connect t h e granular cortical area with surrounding regions of agranular cortex; the latter are also recipients of dense callosal input. These surrounding agranular areas thus indirectly link the somatosensory cortices of the two hemispheres. Figure 7 summarizes this pattern of ipsilateral and contralateral projections. There is some evidence that a similar convergence of ipsilateral and contralateral corticocortical connections may exist in other species. In the monkey the callosal and association projections of somatosensory cortex are organized in discrete “columns” of similar dimensions (Jones e t al., ’75). This similarity raises t h e possibility that in the monkey, as in the rat, ipsilateral and contralateral corticocortical afferents may terminate on the same groups of cortical cells. The results of this study suggest that there are at least two types of recipient cortex within the rat parietal cortex-one which receives primarily specific thalamocortical inputsand one which receives converging ipsilateral and contralateral corticocortical projections. We have suggested that the first type corresponds to the classically defined SmI neocortex, but the functional significance of the agranular cortical zone has not been determined. It is possible that this agranular region represents a third somatosensory area within the rat parietal cortex. There is some evidence that regions surrounding the classical SmI neocortex may receive input from “somatosensory” areas of the thalamus. Killackey and Ryugo 1‘75) have noted a projection from the central intralaminar nucleus to a region of cortex which encompasses both SmI and surrounding cortical zones. This projection is of the “unspecific” (Lorente de No, ’49) type in

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To Contralateral

Thalamus Fig. 7 A schematic representation of the corticocortical connections of parietal cortex. The granular parietal area (Sm I) is essentially devoid of callosal inputs, but projects to ipsilateral areas which are extensively connected with homotopic areas in the contralateral hemisphere. These converging ipsilateral and contralatera1 projections indirectly link the granular parietal areas of the two hemispheres.

that the terminals are found throughout all cortical layers, but are concentrated within layers I and VI. A projection has also been reported from Emmer's ('65) "SII" region of the thalamus to a zone of cortex which partially overlaps the posterior portion of SmI (Donaldsen et al., '75). In addition, Welker ('76) has reported that occasional responses to somatic stimulation may be elicited in agranular zones by stimulation of the same body regions represented by adjacent clusters of granule cells. These anatomical and electrophysiological data suggest t h a t agranular regions surrounding and embedded within the classical SmI may also subserve somatosensory functions. A second possibility is that these agranular cortical areas are regions of convergence from different sensory modalities. Jones and Powell ('69a, '70a) have described converging sensory pathways within the cortex of the rhesus monkey, but such pathways have not been investigated in the rat. An examination of the thalamic and cortical con-

nectivity of the agranular parietal areas might provide further clues to their functional significance. Laminar organization of inputs to parietal cortex

The results of the present study suggest t h a t there is a laminar separation of thalamic and callosal afferents to the parietal cortex. While specific thalamocortical afferents terminate in layer IV and adjacent portions of layer 111 in the rat (Killackey, '731, the callosal afferents terminate primarily in the upper three cortical layers (Heimer et al., '67; Jacobson, '65; Lund and Lund, '70; Ryugo and Killackey, '75) and in portions of layers V and VI (Wise and Jones, '76). A similar distribution of commissural inputs has been noted in the opossum (Ebner, '67; Benevento and Ebner, '73) and hedgehog (Ebner, '69). This laminar separation of inputs stands in direct contrast to what has been noted in the cat (Jones and Powell, '68a, '70b; Jacobson and Marcus,

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’70), rhesus monkey (Jones and Powell, ’69b; Jones et al., ’75; Pandya and Vignola, ’701, chimpanzee (Jacobson and Marcus, ’701, and squirrel monkey (Tigges e t al., ’74; Jones et al., ’75). In these species layer IV, in addition to the supragranular layers, receives dense commissural input. It has been suggested that the pyramidal cells of layers I11 and V are the major recipients of callosal input in the rat (Wise and Jones, ’761, cat (Shoumura, ’74), and monkey (Jones et al., ’75; Jones and Powell, ’73), a hypothesis supported by Golgi analyses (Lorente de No, ’49; Globus and Scheibel, ’67) and electron microscopic studies (Lund and Lund, ’70; Jones and Powell, ’70b). Our data are consistent with this interpretation, since the callosal afferents are concentrated in regions which lack a well-defined granule cell layer. If the target cells of callosal afferents are the same in the rat and other species, how may this difference in laminar distribution be interpreted? One possible explanation is that laminar segregation of inputs occurs in species in which there is a relatively small cortical surface area. Thus, in small-brained mammals like the opossum and hedgehog, one might expect more areal overlap in the distribution of different afferent systems. Indeed, this seems to be the case, as the motor and somatosensory regions in the opossum are virtually completely overlapping (Lende, ’63). Three separate thalamic nuclei project to this motor-sensory amalgam, but the projections from each nucleus terminate in different combinations of cortical layers (Killackey and Ebner, ’73). In species in which the neocortical surface area is great, separate afferent systems may terminate in different areas of cortex and laminar separation may be less important. If this is the case, the rat may represent a midway point in this trend. The present data suggest a t least a partial areal segregation of thalamic and callosal afferents. Bundles of callosal afferents are quite compact as they pass between groups of granule cells in layer IV. However, as demonstrated in figure 8, the terminals of these afferents “fan out” in the supragranular layers and overlap with surrounding granular cortical areas. This pattern has been noted previously in the rat (Wise and Jones, ’76) and opossum (Benevento and Ebner, ’73). Likewise, the thalamic afferents are sparse, but not completely absent, in the callosal recipient zones. This suggests that the

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cortical surface area in the rat may not be large enough t o accommodate completely nonoverlapping zones of commissural and thalamic input. In this case, a combination of partial areal and laminar separation may be necessary. The presence of callosal terminals within layer IV in the cat and monkey may reflect a greater degree of areal separation in these species. Finally, the present data are consistent with previous reports that the callosal afferents do not arise solely from the infragranular layers (Jacobson, ‘65; Jacobson and Trojanowski, ’74; Wise and Jones, ’75; Yorke and Caviness, ’75; Wise and Jones, ’76). However, our results suggest that the supragranular layers also contribute to ipsilateral corticocortical projections, a finding a t odds with a previous report (Jacobson, ’72). Organization of intracortical circuitry in the “barrel field” cortex Within the “barrel field” cortex of the rat, inputs related to individual peripheral receptors are segregated into non-overlapping terminal fields. Each cortical “barrel” represents a single mystacial vibrissa or sinus hair and receives projections from a discrete bundle of thalamocortical afferents (Woolsey and van der Loos, ’70; Killackey, ’73). This segregation of inputs has been demonstrated at each relay of the rat somatosensory system; afferents within the trigeminal nucleus and ventral posterior thalamic nucleus terminate in distinct clusters which resemble those described in the “barrel field” (Killackey and Belford, ’76). The present study suggests that this segregation is not maintained in the efferent projections or intracortical circuitry of the “barrel field” cortex. Ipsilateral corticocortical projections to motor and SmII cortices terminate in homogeneous terminal fields; no evidence of terminal clustering is apparent in either projection even when lesions clearly encroach on a number of cortical “barrels.” Perhaps more significant is the finding that the supragranular layers of the “barrel field” cortex also project upon the underlying layer V in a homogeneous fashion. The clustering of terminals, so apparent in the thalamic projection, is not seen in this intracortical pathway. Studies of corticothalamic projections in the rat (Wise and Jones, ’77a) and corticocortical projections in the mouse (White and De Amicis, ’77) have likewise demonstrated the

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absence of terminal clustering in these corticofugal pathways. Although a recent study has demonstrated that the corticotectal projection from the rat somatosensory cortex is organized in discontinuous patches, these patches do not seem to be related to individual cortical “barrels” (Wise and Jones, ’77b). These data suggest that the segregation of inputs from individual peripheral receptors is a specialization limited to ascending somatosensory pathways in the rat. In fact, the discreteness of projections related to single vibrissae or sinus hairs is not maintained even within the intracortical circuitry of the “barrel field” cortex. LITERATURE CITED Benevento, L. A,, and F. F. Ebner 1973 Theareas andlayers of corticocortical terminations in the visual cortex of the Virginia opossum. J. Comp. Neur., 141: 157-190. Donaldson, L., P. J. Handand A. R. Morrison 1975 Corticalthalamic relationships in the rat. Ekp. Neurol., 47:

448-458. Ebner, F. F. 1967 Afferent connections to neocortex in the opossum (Didelphis uirginianal. J. Comp. Neur., 129:

241-268. 1969 A comparison of primitive forebrain organization in metatherian and eutherian mammals. N. Y. Acad. Sci., 167: 241-257. Ebner, F. F., and R. E. Myers 1962 Commissural connections in the neocortex of monkey. Anat. Rec.,142: 229. 1965 Distribution of corpus callosum and anterior commissure in cat and racoon. J. Comp. Neur., 124: 353-366. Emmers, R. 1965 Organization of the first and second somesthetic regions (SI and SII) in the r a t thalamus. J. a m p . Neur., 124: 215-228. Fink, R. L., and L. Heimer 1967 Two methods for selective silver impregnation of degenerating axons and their synaptic ends in the central nervous system, Brain Res., 4:

369-374. Friede, R. L. 1960 A comparative study of cytoarchitectonics and chemoarchitectonics of the cerebral cortex of the guinea pig. Z. Zellforsch., 52: 482-493. 1966 Topographic Brain Chemistry. Academic Press, New York, pp. 16-131. Globus, A., and A. Scheibel 1967a Synaptic loci on parietal cortical neurons: terminations of corpus callosum fibers. Science, 156: 1127-1129. Goldman, P. S.,and W. J. H. Nauta 1977 Columnar distribution of corticocortical fibers in the frontal association, limbic, and motor cortex of the developing rhesus monkey. Brain Res., 122: 393-413. Hall, R. D., and E. P. Lindholm 1974 Organization of motor and somatosensory neocortex in the albino rat. Brain Res., 66: 23-38. Heath, C. J., and E. G. Jones 1971 Interhemispheric pathways in the absence of a corpus callosum. J. Anat. (London), 109: 253-270. Heimer, L., F.F. Ebner and W.J. H. Nauta 1967 A note on the termination of commissural fibers in the neocortex. Brain Res., 5: 171-177. Hubel, D. G., and T. N. Wiesel 1967 Cortical and callosal connections concerned with t h e vertical meridian of visual fields in the cat. J. Neurophysiol., 30: 1561-1573.

Hughes, A,, and M. E. Wilson 1969 Callosal terminations along the boundary between visual area I and I1 in the rabbit. Brain Res., 12: 19-25. Jacobson, S. 1972 The laminar contributions to the callosal system in the albino rat. Anat. Rec., 169: 346. 1965 Intralaminar, interlaminar, callosal and thalamocortical projections in frontal and parietal areas of t h e albino r a t cerebral cortex. J. Comp. Neur., 124:

131-146. 1970 Distribution of commissural axon terminals in t h e rat neocortex. Ekp. Neurol., 28: 193-205. Jacobson, S., and E. M. Marcus 1970 The laminar distribution of fibers of t h e corpus callosum: a comparative study in t h e rat, cat, rhesus monkey, and chimpanzee. Brain Res., 24: 517-520. Jacobson, S., and J. A. Trojanowski 1974 The cells of origin of the corpus callosum in rat, cat, and rhesus monkey. Brain Res., 74: 149-155. Jones, E. G., H. Burton and R. Porter 1975 Commissural and corticocortical “columns” in the somatic sensory cortex of primates. Science, 190: 572-584. Jones, E. G., and T. P. S. Powell 1968a The commissural connections of the somatosensory cortex in the cat. J. Anat. (London), 103: 433-456. 1968b The ipsilateral cortical connections of the somatic sensory areas in the cat. Brain Res., 9: 71-94. 1969a Connexions of the somatic sensory cortex of the rhesus monkey. I. Ipsilateral cortical connexions. Brain, 92: 504-531. 1969b Connexions of the somatosensory cortex of the rhesus monkey. 11. Contralateral cortical connexions. Brain, 92: 717-730. 1970a An anatomical study of converging sensory pathways within the cerebral cortex of the monkey. Brain, 93: 793-830. 1970b An electron microscopic study of the laminar pattern and mode of termination of extrinsic afferent fibers in the somatic sensory cortex of t h e cat. Phil. Trans. Roy. Soc. London, B. 257: 45-62. 1973 Anatomical organization of the somatosensory cortex. In: Handbook of Sensory Physiology. A. Iggo, ed. Springer-Verlag, Berlin. Karol, E. A., and D. N. Pandya 1971 The distribution of the corpus callosum in the rhesus monkey. Brain, 94:

~

471-486. Killackey, H. P. 1973 Anatomical evidence for cortical subdivisions based on vertically discrete thalamic projections from t h e ventral posterior nucleus to cortical barrels in t h e rat. Brain Res., 51: 326-331. Killackey, H. P.,and G. R. Belford 1976 Discrete afferent terminations in t h e trigeminal pathway of t h e neonatal rat. Anat. Rec., 184: 446. Killackey, H. P.,G. R. Belford, R. Ryugo and D. K. Ryugo 1976 Anomalous organization of thalamocortical projections consequent to vibrissae removal in the newborn rat and mouse. Brain Res., 104: 309-315. Killackey, H. P., and F. F. Ebner 1973 Convergent projectionof three separate thalamic nuclei onto a single cortical area. Science, 179: 283-285. Killackey, H. P., and S. Leshin 1975 The organization of specific thalamocortical projections to t h e posteromdial barrel subfield of the r a t somatic sensory cortex. Brain Rea., 86: 469-572. Killackey, H. P., and D. K. Ryugo 1975 The organization of unspecific thalamic projections to the telencephalon of t h e rat. Anat. Rec., 181: 393. Kunzle, H. 1976 Alternating afferent zones of high and low axon terminal density within t h e macaque motor cortex. Brain Rea., 106: 365-370.

CONNECTIONS OF RAT PARIETAL CORTEX Labedsky, L., and W. Lierse 1968 Die entwicklung der succinodehydrogenaseaktivitat in gehirn der Maus wahrend der postnatalzeit. Histochemie., 12: 130-151. Lende, R. A. 1963 Sensory representation of the cerebral cortex of the opossum (Didelphis uirginiana). J. Comp. Neur., 121: 395-404. Lorente de No, R. 1949 Cerebral cortex: Architecture, intracortical connections, motor projections. In: Physiology of the Nervous System. J . F. Fulton, ed. Second Ed. Oxford University Press, New York, pp. 274-313. Lund, J. S., and R. D. Lund 1970 The termination of callosal fibers in the paravisual cortex of the rat. Brain Res., 17: 25-45. Morrison, A. R. 1967 Contrasting corticocortical connections of somatosensory areas I and 11. Anat. Rec., 157: 290-291. Myers, R. E. 1962 Cammissural connections between occipital lobes in the monkey. J. Comp. Neur., 118: 1-16. Nauta, H.J., A. B. Butler and J . A. Jane 1973 Some observations of axonal degeneration resulting from superficial lesions of the cerebral cortex. J. Comp. Neur., 150: 349-360. Pandya, D. N., D. Gold and T. Berger 1969 Interhemispheric connections of the precentral motor cortex in th e rhesus monkey. Brain Res., 15: 594-596. Pandya, D. N., and L. A. Vignola 1969 Interhemispheric projections of the parietal lobe in th e rhesus monkey. Brain Res., 15: 49-65. Ryugo, R., and H. P. Killackey 1975 Corticocorticalconnections of the barrel Weld of r at somatosensory cortex. Neurosci. Abstr., 1: 198. Shanks, M. F., A. J . Rockel and T. P. S. Powell 1975 The commissural fiber connections of th e primary somatic sensory cortex. Brain Rea., 98: 166-171. Shoumura, K. 1974 An attempt to relate the origin and distribution of commissural fibers to the presence of large and medium pyramids in the cat’s visual cortex. Brain Res., 67: 13-25. Tigges, J., W. B. Spatz and M. Tigges 1974 Efferent corticocortical fiber connections of area 18 in the squirrel monkey. J . Camp. Neur., 158: 219-236. Welker, C. 1971 Microelectrode delineation of fine grain somatotopic organization of SmI cerebral neocortex in albino rat. Brain Res., 26: 259-275.

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1976 Receptive fields of barrels in the somatosensory neocortex of the rat. J. Comp. Neur., 166: 173-190. Welker, C., and M. M. Sinha 1972 Somatotopic organization of SmII cerebral neocortex in albino rat. Brain Res., 37: 132-136. Welker, C., and T. A. Woolsey 1974 Structure of layer IV in the somatosensory neocortex of the rat: Description and comparison with themouse. J. Comp. Neur., 158: 437-453. White, E. L., and R. A. DeAmicis 1977 Afferent and efferent projections of the region in the SmI cortex which contains the posteromedial barrel subfield. J. Comp. Neur., 175: 456-482. Wilson, M. E. 1968 Corticocortical connections of the cat visual areas. J. Anat. (London), 102: 375-386. Wise, S. P. 1975 The laminar organization of certain afferent and efferent fiber systems in the r at somatosensory cortex. Brain Res., 90: 139-142. Wise, S. P.,andE. G. Jones 1976 Theorganization and postnatal development of the commissural projection of the rat somatic sensory cortex. J. Comp. Neur., 168: 313-344. 1977a Cells of origin and terminal distribution of descending projections of t h e r at somatic sensory cortex. J. Comp. Neur., 175: 129-158. 1977b Somatotopic and columnar organization in the corticotectal projection of the rat somatic sensory cortex. Brain Res., 133: 223-235. Woolsey, C. N., and D. H. Lemessurier 1948 The pattern of cutaneous representation in t h e rat’s cerebral cortex. Fed. Proc., 7: 137. Woolsey,T.A., and H. van der Loos 1970 The structural organization of layer IV in the somatosensory region (SI) of mouse cerebral cortex. The description of a cortical field composed of discrete cytoarchitectonic units. Brain Res., 17: 205-242. Woolsey, T.A., C. Welker and R. H. Schwartz 1975 Com parative anatomical studies of the SmI face cortex with special reference to the occurrence of “barrels” in layer IV. J. Comp. Neur., 264: 79-94. Yorke, C. H., and V. S. Caviness 1975 Interhemispheric neocortical connections of the corpus callosum in the normal mouse: A study based on anterograde and retrograde methods. J. Comp. Neur., 164: 233-246.

C A Fink-Heimer preparation following lesion of the ventral posterior nucleus. An interruption in the thalamic field is apparent, as is the reduction of granule cell density in the same zone. This narrow “athalamic” region corresponds to the callosal recipient strip illustrated in A. Scale, 200 Fm.

recipient zone.

B An adjacent Nissl-stained section demonstrates the interruption of the granule cell layer in the callosal

A A narrow strip of terminal degeneration resulting from transection of the corpus callosum (Fink-Heirner material).

8 Photographic montages of coronal sections through parietal cortex.

EXPLANATION OF FIGURES

PLATE 1

CONNECTIONS OF RAT PARIETAL CORTEX Rebecca M. Akera and Herbert P. Killackey

PLATE 1

PLATE 2

CONNECTIONS OF RAT PARIETAL CORTEX Rebecca M. Akera and Herbert P . Killackey

EXPLANATION OF FIGURE

9 Coronal section through parietal cortex stained for succinic dehydrogenase activity. The darkly-staining band, which corresponda to the zone of dense thalamic input, is interrupted by a region of reduced enzyme activity. The pattern of thalamic projections revealed by this technique closely resembles that seen in Fink-Heimer material. Scale, 500 fim.

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CONNECTIONS OF RAT PARIETAL CORTEX Rebecca M. Akers and Herbert P. Killackey

PLATE 3

EXPLANATION OF FIGURE

10 Photographic montage of a flattened tangential section stained for succinic dehydrogenaee activity. This technique reveals discontinuities in the thalamic terminal field. The pattern of thalamic projections demonstrated by this method closely resembles the arrangement of granule cell aggregates within the parietal cortex. Scale, 1 mm.

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PLATE 4 EXPLANATION OF FIGURE

11 Photographic montage of a terminal field resulting from a lesion of granular parietal cortex (Fink-Heimer material, coronal section). Degenerating fibers can be seen passing tangentially from the lesion site in layers V and VI. These fibers terminate primarily within layers 1-111 of the adjacent agranular cortex. Scale, 200 pm. Inset illustrates position of the terminal field relative to the lesion site.

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CONNECTIONS OF RAT PARIETAL CORTEX Raherrn M

Alrmrn n d

Uarhort P

PLATE 4

Kill~rlrnu

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PLATE 5 EXPLANATION OF FIGURE

12 Photographic montage of a coronal Nissl section adjacent to that depicted in figure

11. Arrows indicate the termination of the well-defined granule cell layer. The ipsilateral terminal field illustrated in figure 11 lies immediately adjacent to the boundary of the granular cortical zone. Scale, 200 pm.

534

CONNECTIONS OF RAT PARIETAL CORTEX Rebecca M. Akera and Herbert P. Killackey

PLATE 5

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PLATE 6 EXPLANATION OF FIGURE

13 Photographic montage of a terminal field resulting from a lesion involving layers 1-111 of the "barrel field" cortex (coronal section, Fink-Heimer material). Note the absence of clustering in the band of terminal degeneration which lies within layer V beneath the lesion site. Scale, 200 pm.

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CONNECTIONS OF RAT PARIETAL CORTEX Rebecca M. Akem and Herbert P. Killackey

PLATE 6

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Organization of corticocortical connections in the parietal cortex of the rat.

Organization of Corticocortical Connections in the Parietal Cortex of the Rat REBECCA M. AKERS AND HERBERT P.KILLACKEY Department of Psychobiology, Un...
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