Brain Research, 145 (1978) 225 238 :% Elsevier/North-Holland Biomedical Press
225
T H A L A M I C A F F E R E N T S TO THE LIMBIC CORTEX IN T H E CAT STUDIED WITH T H E M E T H O D OF R E T R O G R A D E A X O N A L T R A N S P O R T OF HORSERADISH PEROXIDASE
K. NIIMI, M. NIIMI and Y. OKADA Fhird Department o/' Anatomy, Okayama University Medical School, Okayama (Japan)
(Accepted August 12th, 1977)
SUMMARY Thalamic afferents to the limbic cortex in the cat were studied with the method of retrograde axonal transport of horseradish peroxidase. The anterior limbic region receives fibers largely from the anteromedial nucleus and partly from the anterodorsal and anteroventral nuclei. There appears to be a dorsoventral organization of cortical projections of the anteromedial nucleus to the anterior limbic region. The cingular area has its main input from the anteroventral and anteromedial nuclei. The lower bank and fundus of the splenial sulcus receive fibers from the anteroventral nucleus, particularly its parvocellular part. The retrosplenial area receives projections from the anterodorsal, anteroventral and anteromedial nuclei. The agranular retrosplenial area (area 30) receives hardly any fibers from the anterior thalamic nuclei. The postsubicular and presubicular areas receive cortical afferents from the anterodorsal, anteroventral (both magnocellular and parvocellular parts) and anteromedial nuclei. In addition, the limbic cortex receives many fibers from the dorsal lateral, medial pulvinar and lateral pulvinar nuclei, and few fibers from the intralaminar and midline nuclei.
INTRODUCTION It is generally assumed that the anteromedial nucleus projects to the anterior portion of the cingulate cortex, the anteroventral nucleus to the middle and posterior areas of the cingulate cortex, and the anterodorsal nucleus to the posterior cingulate cortex, including the retrosplenial area2,4-6,ta,1a,25,28,al,a2,a4,as. Recently, Niimi et al. 2~, using the Nauta-Gygax and Fink-Heimer methods in the cat, found that the cortical projections of the anterior thalamic nuclei overlap each other more than generally thought. According to them, although the anterior limbic region receives
226 fibers only from the anteromedial nucleus, the cingular area receives fibers from the anteroventral and anteromedial nuclei, and the retrosplenial and postsubicular areas from the anterodorsal, anteroventral and anteromedial nuclei. The present study attempts to confirm these findings using the method of retrograde axonal transport of horseradish peroxidase (HRP) 1'~,14. MATERIAL AND METHODS Fifteen normal adult cats (18 cases) were used in the present study. During sterile surgical procedures, injections of 0.054).1 #1 of a 30% solution of H R P (Sigma VI) in 0.9 ~o sterile saline were made unilaterally or bilaterally into various areas of the limbic cortex, since no evidence for crossed cortical projections of the anterior thalamic nuclei was known. Under Nembutal anesthesia, the animals were placed in a stereotaxic head holder. H R P was injected by one penetration of a 1 #1 Hamilton microsyringe needle held in a microinjection holder mounted on an electrode carrier through a trephined hole in the calvarium. After survival of 48 h, the animals were deeply anesthetized and fixed by transcardiac perfusion with 200 ml
I
i i
IIR,
1
o J "~°" ....
![ '
:
L
,IIIR
, i
/ ]
,,
j
•
:'Pr
Fig. 1. Diagram to show the site and extent of HRP injections drawn on a standardized outline of the right medial cortex in all the cats studied. In this figure cortical injections madein either or both left and right cerebral hemispheres are all depicted onthe right hemisphere to facilitate comparison. The numbers indicate cat numbers. Blackened areas and surrounding white areasindicate lhe central and peripheral areas of the injection sites. Vertical lines represent needle tracks: The banks of sulci are indicated by areas lying close to the sulci. AbbreviatiOns for this and all Subsequent figures are found listed after the Discussion.
227 of 0.1 M phosphate buffer (pH 7.4) containing 10°/o sucrose, followed by 2000 ml of a mixture of 5 ~o formalin-1 ~o glutaraldehyde in the phosphate buffer. The brains were removed from the skull, cut into blocks and immediately transferred to the phosphate buffer containing 30 ~ sucrose, and then stored in the same fluid overnight at 4 °C. Frozen sections through the cortical injection sites and the thalamus were cut at 60 # m thickness in the stereotaxic plane. Sections were collected in 0.1 M phosphate buffer, pH 7.6. After rinsing in the phosphate buffer 3 times, every fourth section was transferred to an incubation medium containing 0.05 ~o 3,3'-diaminobenzidine tetrahydrochloride and 0.01 ~ HzO2 in Tris buffer. The sections were incubated in this medium for 20-30 min at room temperature, transferred through 3 changes of distilled water and mounted on slides with alcoholic gelation. Sections were lightly counterstained with 0.1 ~ cresyl violet in order to determine the exact location of the HRP-labeled cells. The injection sites were reconstructed and indicated on a standardized diagram of the medial cortex of the cerebral hemisphere (Fig. 1). Neurons were interpreted as labeled when they contained the reaction products of H R P in distinct granules with the cell soma and proximal dendrites. The stereotaxic atlas of Reinso-Squ/lrez 29 was used for the stereotaxic injection of H R P into the limbic cortex. However, the limbic cortical areas were defined, for the most part, according to the cytoarchitectural study of Rose and Woolsey 31 in the cat. They divided the limbic cortex into the anterior and posterior limbic regions, of which the latter is composed of the cingular and retrosplenial areas. In addition they defined the postsubicular area, which may be regarded as part of the presubicular area 30. In the present paper, the term presubicular area will be employed in a narrow sense, excluding the postsubicular area. The thalamic nuclei were classified and named following Niimi and Kuwahara 21.
SS~ S
CATIOR
~
SS
CAT21L
Fig. 2. Transverse sections through the cerebral hemisphere to show the maximal extent of HRP injections in cats 10R, 21R, 25R and 21L. Blackened areas and surrounding stippled areas indicate the central and peripheral areas of the injection sites. Broken lines represent needle tracks.
228
I # CAI
,:,,,
Fig. 3. Distribution of HRP-labeled cells (crosses) in the thalamus of cat 9R. Transverse sections, RESULTS
(l) Cases with injection sites lying largely in the anterior timbic region In cats 9R, 14R, and IOR. H R P was injected stereotaxicatly into the anterior limbic region. The injection needle was directed vertically, passing through cortical area 5 and the lips of the cruciate sulcus (including area 6) to reach the anterior limbic region. The injection site in cat 10R was confined largely to area 6 (see ref. 8) and the adjoining portion of the anterior limbic region (Figs. 1 and 2). Numerous labeled cells were found in the ventromedial part of the anteromedial nucleus, whereas only a few cells were labeled in the dorsolateral part (Figs. 3 and 7A). Within the ventromedial part of the anteromedial nucleus, labeled cells increased in number as the injection site was displaced more ventrally (Table !). Occasional cells were labeled in the anterodorsal and anteroventral nuclei. Labeled cells were also detected in the paracentral, medial central, rhomboid and reuniens nuclei (Fig. 3). In cases with injection sites involving area 6, labeled cells were seen in the ventral anterior and ventral lateral nuclei (cats 10R and 14R). Injections in the anterior limbic region adjacent to the granular frontal cortex led to labeling in the dorsomedial, submedial, ventral medial and paratenial nuclei (cat 9R). (II) Cases with injection sites centered in the cingular area In cats l l R , 13R, and 12L, the injection needle passed vertically through the cortex of the suprasplenial and splenial gyri (area 17) and reached the cingular area. The injection sites in cats 11R and 13R were present in the anterior portion of the cingular area, whereas the injection site in cat 12L was in the posterior portion (Fig. 1).
229 A considerable number of labeled cells were seen scattered in the magnocellular part of the anteroventral nucleus. Scarcely any labeled cells were found in the parvocellular part. In cats I l R and 13R, the anteromedial nucleus contained many labeled cells, particularly in the ventromedial part (Fig. 4A). In cat 12L, however, the labeled cells were much more numerous in the dorsolateral part than in the ventromedial part. Labeling in the anterodorsal nucleus was found only in cat 11R. In the dorsal lateral nucleus labeled cells were detected occasionally in cats I IR and 13R, but were numerous in cat 12L where labeling was also found in the medial and lateral pulvinar nuclei. Very few, if any, labeled cells were found in the lateral geniculate nucleus. In cats I 1R and 13R, a fair number of labeled cells were detected in the paracentral nucleus, and occasional labeled cells in the lateral central, ventral anterior, ventral lateral, ventral medial and submedial nuclei. In cats 21R, 25R and 21L, the injection needle passed vertically through the lateral gyrus and the underlying white matter and reached the lower bank (cats 21R and 25R) or fundus (cat 21L) of the splenial sulcus (Figs. 1 and 2). A few cells were labeled in both magnocellular and parvocellular parts of the anteroventral nucleus in cats 21R and 25R (Fig. 4B). In cat 21L labeling was found only in the parvocellular part. In these cats no labeled cells were seen in the anteromedial nucleus. A large number of labeled cells were detected in the dorsal lateral and medial pulvinar nuclei, and some labeled cells in the posterior lateral, lateral pulvinar and ventral anterior nuclei. Only occasional cells were found in the lateral central nucleus, in cat 21L very few cells were labeled in the paracentral, medial central and ventral nuclei.
A
C A T 11R
CA ! 2 5 H
Fig. 4. Distribution of HRP-labeled cells (crosses) in the thalamus of cats 11R (A) and 25R (B). Transverse sections.
230
T,
P1
..-/
CAT 7R
~
m
PC
x
= CM
Fig. 5. Distribution of HRP-labeled cells (crosses) in the thalamus of cat 7R. Transverse sections.
(111) Cases with injection sites largely confined to the retrosplenial area In cats 7L, 19R, 19L. 7R and 18R, HRP was injected into the retrosplenial area. The injection needle passed vertically through the cortex of the suprasplenial and splenial gyri into the anterodorsal part of the retrosptenial area in cats 7L. 19L and 19R, whereas the needle passed through the suprasylvian cortex and the underlying white matter in cats 7R and 18R (Fig. 1). The injection site of cat 18R corresponded to the agranular part of the retrosplenial area (area 30 of Brodmann3). In cats 7L, 19R, 19L and 7R. a large number of labeled cells were concentrated in the anterodorsal nucleus and the magnocellular part of the anteroventral nucleus (Figs. 5 and 7C). Numerous labeled cells were also found in both dorsolateral and ventromedial parts of the anteromedial nucleus (Fig. 7B). The parvocellutar part of the anteroventral nucleus contained only occasional labeled cells, which may have resulted from a slight leakage of H R P along the injection needle passing through the lower lip of the splenial sulcus. It should be noted that a large number of labeled cells were detected in the dorsal lateral nucleus, particularly its dorsal portion, and a lesser number in the most dorsal parts of the medial and lateral pulvinar nuclei (Fig. 5). No labeling of cells was found in the posterior lateral nucleus. Occasional cells were labeled in the intralaminar and midline nuclei. In addition, few labeled cells were encountered in the ventral anterior, ventral medial and submedial nuclei in cats 19R and 19L (Table 1). In cat 18R no labeling was seen in the anterior nuclei, except for very few cells in the parvocellular part of the anteroventrat nucleus. A large number of labeled cells were found in the dorsal portions of the dorsal lateral and medial pulvinar nuclei, and less numerous cells were labeled in the most dorsal part of the lateral pulvinar nucleus.
231
(IV) Cases with injection sites in the postsubicular and presubicular areas In cats 6R, 8R, 4R and 20L, H R P was injected into the postsubicular and presubicular areas. The injection needle passed vertically through the cortex of the middle suprasylvian gyrus and the underlying white matter. The injection sites in cats 6R, 8R and 4R involved both postsubicular and presubicular areas, but the injection site in cat 20L was present in the anterodorsal portion of the presubiculum, extending dorsally beyond the limit of the presubiculum (Fig. 1). In cats 6R and 8R, numerous labeled cells were distributed in the anterodorsal and anteroventral nuclei, and some labeled cells were found in the anteromedial nucleus, particularly its ventromedial part (Figs. 6A and 7D). It should be mentioned that the anteroventral nucleus contained labeled cells in both magnocellular and parvocellular parts. A large number of labeled cells were concentrated in the dorsal part of the dorsal lateral nucleus and the most dorsal portion of the medial pulvinar nucleus, and some cells were labeled at the dorsal periphery of the lateral pulvinar nucleus. In addition, occasional labeled cells were seen in the paracentral, lateral central and midline nuclei. In cat 4R very few labeled cells were detected in the anterior nuclei, but abundant cells were labeled in the dorsal part of the dorsal lateral nucleus and the dorsal periphery of the medial and lateral pulvinar nuclei. In cat 20L more labeled cells were found in the anterodorsal and anteroventral nuclei, although no labeling was seen in other thalamic nuclei, except for the dorsal lateral and reuniens nuclei (Fig. 6B). DISCUSSION
(I) Anterior limbic region Our results reveal that the anterior limbic region receives fibers largely from the
A
B
CAT6R
CAT 20L
Fig. 6. Distribution of HRP-labeled cells (crosses) in the thalamus of cats 6R (A) and 20L (B). Transverse sections.
233 anteromedial nucleus and partly from the anterodorsal and anteroventral nuclei (cats 9R, 14R and 10R). The labeled cells in the ventromedial part of the anteromedial nucleus increase in number with the ventral displacement of the injection site (Table I). This appears to indicate a dorsoventral organization of the cortical projections of the anteromedial nucleus to the anterior limbic region, confirming the study of Niimi et al. ~ using the Nauta method. A considerable number of labeled cells were found in the dorsomediak submedial and ventral medial nuclei, in addition to the anteromedial nucleus following HRP injection into the anteroventral portion of the anterior limbic region (cat 9R). This indicates that there is considerable overlap of the projection areas of the anteromedial nucleus and the dorsomedial, submedial and ventral medial nuclei which were all reported to send fibers to the granular frontal cortex (Niimi et al.~4). Beckstead ~ stated that the respective thalamocortical projections of the dorsomedial and anteromedial nuclei overlap over a wide region of the anterior medial cortex in the rat. In cat 9R a few labeled cells were seen in the paratenial nucleus. According to Niimi et al. (unpublished data), some cells in this nucleus were labeled following injections of HRP in the frontal granular cortex.
(ll) Cingular area According to the present study, the cingular area receives a major input from the anteroventral and anteromedial nuclei (cats l lR, 13R and 12L). The results obtained with the Nauta silver technique (Niimi et al. 26) revealed that the projection of the anteroventral nucleus overlaps that of the anteromedial nucleus in the cingular area. Krieg 1l and Meyer et al. is described the projection of the anteromedial nucleus to the posterior part of the cingular cortex. HRP injection into the more ventral portion in the cingular area tended to result in labeling of cells in the more medial portion of the anteroventral nucleus (cat 7L). This may indicate a mediolateral organization of the cortical projections of the anteroventral nucleus, as suggested by Domesick 6 in the rat. The Nauta study of Niimi et al. 2~ suggests a mediolateral and anteroposterior organization of the cortical projections of the anteroventral nucleus. Our results indicated that injections of HRP into the lower bank and fundus of the splenial sulcus lead to cell labeling in the parvocellular part of the anteroventral nucleus, in addition to the magnocellular part (cats 21 L, 21R and 25R). The projections of the parvocellular part of the anteroventral nucleus to the lower bank of the splenial sulcus were suggested by Niimi and Sprague '~2 using the method of retrograde cell degeneration and later confirmed by Niimi et al. 26 with the use of the Nauta method. (lll) Retrosplenial, postsubicular and presubicular areas Our results reveal that the retrosplenial area receives fibers from the anterodorsal, anteroventral and anteromedial nuclei (cats 7L, 19R, 19L and 7R). In most of these cases, very few labeled cells were found in the parvocellular part of the anteroventral nucleus, but this may be due to the involvement of the lower lip of the splenial sulcus in the injected area (Table 1). According to the Nauta study of Niimi
234
t
ill
u~tlll qi
I iil ©
I .u i
i
f
~m/
i i
III
~if:
-H -i! I i~
~-HI
I L
I11
li~!t
III
I J ,H
-!i-
[I
d
i ~i ~ H i t
I
J 1 ~J
ii
I L
J ~! J
t
©
E
I I H ~-H
it
I
I -h
fi
~L ~
~i i ¸
f i
.,c
I
--
_o
B~
:,3
=~
235 et al. 26, the cortical projections of the anterodorsal, anteroventral and anteromedial nuclei overlap in the retrosplenial area. Domesick 6 stated that the anteromedial nucleus projects to the anterior limbic region and presubiculum but sends no fibers to the retrosplenial area. Our results indicate that scarcely any labeled cells were present in the anterior thalamic nuclei following HRP injection into the agranular retrosplenial area (cat 18R), confirming the results of Niimi et al. 26 using the Nauta method. Niimi (unpublished data) found terminal degeneration in the postsubicular and presubicular areas following lesions in the anterodorsal, anteroventral and anteromedial nuclei, in essential agreement with the results of Domesick 5,6 in the rat. Our data also demonstrated that injections of H R P into these areas resulted in labeling of cells particularly in these anterior nuclei, of which the anteroventral nucleus contained labeled cells in both magnocellular and parvocellular parts (cats 6R, 8R, 4R and 20L). Within the dorsal lateral nucleus, labeled cells appeared in all cases with injection sites in the limbic cortex, except for the anterior limbic region (Table I). The labeled cells were most numerous following injections of HRP into the retrosplenial, postsubicular and presubicular areas and the cortex within the splenial sulcus. The projections of the dorsal lateral nucleus to the cingular and suprasylvian cortices have been demonstrated by the degeneration methods 16,17,e°. In our cases with injection sites in and near the fundus of the splenial sulcus (area 19 of Otsuka and Hassler27), labeled cells appeared in the posterior lateral nucleus (cats 21L and 25R). Niimi and lnoshita 2° stated that the posterior lateral nucleus projects heavily to the banks and bottom of the splenial sulcus, in addition to the suprasylvian and lateral gyri. According to our results, labeled cells were detected in the medial and lateral pulvinar nuclei following injections of HRP in the postsubicular and presubicular areas and in the middle and posterior parts of the retrosplenial and cingular areas, including the lower bank and fundus of the splenial sulcus (Table D. It should be noted that labeled cells were seen scattered throughout the medial and lateral pulvinar nuclei following injections of HRP into the lower bank and fundus of the splenial sulcus, while these were concentrated in the most dorsal parts of these nuclei following H R P injection into the retrosplenial, postsubicular and presubicular areas. It has been demonstrated by the Nauta method that the lateral pulvinar nucleus sends fibers to the suprasylvian cortex and the cortex within the splenial sulcus 7,23. The possibility that some of the labeled cells in the lateral pulvinar and dorsal lateral nuclei may have resulted from the leakage of HRP along the injection needle cannot be ruled out, since the needle passed vertically through the middle suprasylvian gyrus in cats 7R, 18R, 6R, 8R, 4R and 20L. In most of our cases labeled cells were seen scattered in the paracentral and lateral central nuclei. Within the rhomboid, medial central and reuniens nuclei, a few labeled cells were encountered in many cases (Table I). Jones and Leavitt 9, using the HRP method, demonstrated that the intralaminar nuclei project sparsely and diffusely upon the cerebral cortex. There has yet been no detailed account of the cortical projections of the midline thalamic nuclei.
236 A lair n u m b e r o f labeled cells were f o u n d in the ventral a n t e r i o r a n d ventral lateral nuclei following injections into a r e a 6 a n d n e i g h b o r i n g areas (cats 10R, 14R, I I R and 13R). it has been d e m o n s t r a t e d that these nuclei project to areas 4 and 6 a n d to areas 5 and 7 (see refs. 10 a n d 19). In cats 9R, 14R a n d 10R, the injection needle passed t h r o u g h cortical a r e a 5 and the underlying white matter, but in cat 9R no labeling was f o u n d in the ventral a n t e r i o r a n d ventral lateral nuclei. The injection needle p a s s e d vertically t h r o u g h the lateral, s u p r a s p l e n i a l and splenial gyri (area 17) in cats I1R, 13R, 21R, 21L, 25R, 12L, 7L, 19R and 19L. H o w e v e r very few, if any, labeled cells were detected in the lateral geniculate nucleus, Since the injection needle passed vertically t h r o u g h the cortex o f the medial surface o f the hemisphere in m a n y cases, d a m a g e to the cingulum by the injection needle a p p e a r e d to be only slight, in cats 7R, 18R, 6R, 8R, 4 R a n d 20L, the needle traversed the cingulum but was located too c a u d a l l y to involve m a n y fibers o f passage in the cingulum. ABBREVIATIONS AD AMD. AMV AV AVM AVP CD Cg CL CM LA LD LP
= : : =
anterodorsal nucleus dorsolateral part of anteromedial nucleus ventromedial part of anteromedial nucleus anteroventral nucleus magnocellular part of anteroventral nucleus parvocellular part of anteroventral nucleus dorsal central nucleus cingular area lateral central nucleus medial central nucleus anterior timbic region dorsal lateral nucleus posterior lateral nucleus
MD Pc PL PM Pr Ps Pt R Rh Rs Rt SC Sm SS VA VL VM
dorsomedial nucleus paracentral nucleus lateral pulvinar nucleus medial pulvinar nucleus presubicular area postsubicular area paratenial nucleus reuniens nucleus rhomboid nucleus . retrosplenial area thalamic reticular nucleus cruciate sulcus submedial nucleus splenial sulcus ventral anterior nucleus ventral lateral nucleus ventral medial nucleus
ACKNOWLEDGEMENTS W e wish to express o u r g r a t i t u d e to Professor J a m e s M. Sprague, D e p a r t m e n t o f A n a t o m y , University o f Pennsylvania, for his helpful suggestions in the p r e p a r a tion o f this paper.
REFERENCES 1 Beckstead, R. M.,Convergent thatamicandmesencephalicprojectionstotheanterior medialcortex in the rat, J. eomp. NeuroL, t66 (1976) 403-416. 2 Bodian, D., Studies on the diencephalon of the Virginia opossum. Part I11. The thalamo-cortical projection, J. comp. NeuroL, 77 0942) 525-575. 3 Brodmann, K., Vergleiehende Lokalisationslehre der Grosshirnrinde, Barth,: Leipzig, 1909. 4 Clark, W. E. Le Gros and Boggon, R. H., On the connexions of the anterior nucieus of the thalamus, J. Anat. (Lond.), 67 (1933) 215-226. 5 Domesick, V. B., The fascieulus einguli in the rat, Brain Research, 12 (1970) 19-32.
237 6 Domesick, V. B., Thalamic relationships of the medial cortex in the rat, Brain Behav. Evol., 6 (1972) 457-487. 7 Graybiel, A. M., Some ascending connections of the pulvinar and nucleus lateralis posterior of the thalamus in the cat, Brain Research, 44 (1972) 99 125. 8 Hassler, R. und Muhs-Clement, K., Architektonischer AuPoau des sensomotorischen und parietalen Cortex der Katze, J. Hirnforsch., 6 (1964) 377-420. 9 Jones, E. G. and Leavitt, R. Y., Retrograde axona[ transport and the demonstration of nonspecific projections to the cerebral cortex and striatum from thalamic intralaminar nuclei in the rat, cat and monkey, J. comp. NeuroL, 154 (1974) 349-378. 10 Kobayashi, E. and Niimi, K., Cortical projections of the anterior and lateral ventral nuclei in the cat, Acta anat. Nippon, 48 (1973) 62-63. I1 Krieg, W. J. S., Connections of the cerebral cortex. 1. The albino rat. C. Extrinsic connections, J. comp. Neurol., 86 (1947) 267 394. 12 Kristensson, K. and Olsson,Y., Retrograde axonal transport of protein, Braht Research, 29 (1971) 363-365. 13 Lashley, K. S., Thalamo-cortical connections of the rat's brain, J. comp. Neurol., 75 (1941) 67-121. 14 LaVail, J. H. and LaVail, M. M., Retrograde axonal transport in the central nervous system, Science, 176 (1972) 1416-1417. 15 Lewis, P. R. and Shute, C. C. D., The cholinergic limbic system: projections to hippocampal formation, medial cortex, nuclei of the ascending cholinergic reticular system, and the subformical organ and supra-optic crest, Brain, 90 (1967) 521-540. 16 Locke, S., Angevine, J. B. Jr. and Yakovlev, P. I., Limbic nuclei of thalamus and connections of limbic cortex. 1I. Thalamo-cortical projection of the lateral dorsal nucleus in man, Arch. Neurol. (Chic.), 4 (1961) 355-364. 17 Locke, S., Angevine, J. B. Jr. and Yakovlev, P. 1., Limbic nuclei of thalamus and connections of limbic cortex. VI. Thalamo-cortical projection of lateral dorsal nucleus in cat and monkey, Arch. Neurol. (Chic.), 11 (1964) 1-12. 18 Meyer, A., Beck, E. and McLardy, T., Prefrontal leucotomy: a neuroanatomical report, Brain, 70 (1947) 1849. 19 Mizuno, N., Konishi, A., Sato, M., Kawaguchi, S., Yamamoto, T., Kawamura, S. and Yamawaki, M., Thalamic afferents to the rostral portions of the middle suprasylvian gyrus in the cat, Exp. Neurol., 48 (1975) 79-87. 20 Niimi, K. and lnoshita, H., Cortical projections of the lateral thalamic nuclei in the cat, Proc. jap. Acad., 47 (1971) 664-669. 21 Niimi, K. and Kuwahara, E., The dorsal thalamus of the cat and comparison with monkey and man, J. Hirtforsch., 14 (1973) 303 326. 22 Niimi, K. and Sprague, J. M., Thalamo-cortical organization of the visual system in the cat, J. comp. Neurol., 138 (1970) 219-250. 23 Niimi, K., Kadota, M. and Matsushita, Y., Cortical projections of the pulvinar nuclear group of the thalamus in the cat, Brain Behav. Evol., 9 (1974) 422 457. 24 Niimi, K., Matsushita, Y., Matsuoka, H. and Okada, Y., Cortical projections of the submedial and medial ventral nuclei of the thalamus in the cat, Anat. Ree., 187 (1977) 774. 25 Niimi, K., Nakano, T., Koizuka, M. and Ichinona, M., Experimental-anatomical studies on the cortical connections of the anterior thalamic nuclei in carnivores, Okajimas Folia anat. jap., 38 (1962) 95-127. 26 Niimi, K., Niimi, M. and Kawamura, S., Cortical projections of the anterior thalamic nuclei in the cat. In Proe. Xth Int. Congr. Anatomists, Tokyo, 1975, p. 193. 27 Otsuka, R. und Hassler, R., Ueber AuPoau und Gliederung der corticalen Sehsph~ire bei der Katze, Arch. Paychiat. Nervenkr., 203 (1962) 212-234. 28 Pribram, K. H. and Fulton, J. F., An experimental critique of the effects of anterior cingulate ablations in monkey, Brain, 77 (1954) 34-44. 29 Reinso-Squ~.rez, R., Topographischer Hirnatlas der Katze fiir Experimental-Physiologische Untersuchungen, Merck, Darmstadt, 1961. 30 Rose, M., Cytoarchitektonischer Atlas der Grosshirnrinde des Kaninchens, J. Psychol. Neurol. (Lpz.), 43 (1931) 353~440. 31 Rose, J. E. and Woolsey, C. N., Structure and relations of limbic cortex and anterior thalamic nuclei in rabbit and cat, J. comp. NeuroL, 89 (1948) 279 348. 32 Stoffels, J., La projection des noyaux ant6rieurs du thalamus sur l'6corce interh6misph6rique; 6tude anatomo-exp6rimentale, J. belge Neurol. Psychiat., 39 (1939) 743-776, 783-833.
238 33 Walker, A. E., An experimental study of the thalamo-cortical projection of the macaque monkey, J. comp. Neurol., 64 (1936) 1--39. 34 Waller, W. H., Topographical relations of cortical lesions to thalamic nuclei in the albino rat, J. comp. Neurol., 60 (1934) 237 270. 35 Yakovlev, P. l., Locke, S., Koskoff, D. Y. and Patton, R. A., Limbic nuclei of thalamus and connections of limbic cortex: I. Organization of the projections of the anterior group of nuclei and of the midline nuclei of the thalamus to the anterior cingulate gyrus and hippucampal rudiment in the monkey, Arch. Neurol. (Chic.), 3 (1960) 620-641.
225
T H A L A M I C A F F E R E N T S TO THE LIMBIC CORTEX IN T H E CAT STUDIED WITH T H E M E T H O D OF R E T R O G R A D E A X O N A L T R A N S P O R T OF HORSERADISH PEROXIDASE
K. NIIMI, M. NIIMI and Y. OKADA Fhird Department o/' Anatomy, Okayama University Medical School, Okayama (Japan)
(Accepted August 12th, 1977)
SUMMARY Thalamic afferents to the limbic cortex in the cat were studied with the method of retrograde axonal transport of horseradish peroxidase. The anterior limbic region receives fibers largely from the anteromedial nucleus and partly from the anterodorsal and anteroventral nuclei. There appears to be a dorsoventral organization of cortical projections of the anteromedial nucleus to the anterior limbic region. The cingular area has its main input from the anteroventral and anteromedial nuclei. The lower bank and fundus of the splenial sulcus receive fibers from the anteroventral nucleus, particularly its parvocellular part. The retrosplenial area receives projections from the anterodorsal, anteroventral and anteromedial nuclei. The agranular retrosplenial area (area 30) receives hardly any fibers from the anterior thalamic nuclei. The postsubicular and presubicular areas receive cortical afferents from the anterodorsal, anteroventral (both magnocellular and parvocellular parts) and anteromedial nuclei. In addition, the limbic cortex receives many fibers from the dorsal lateral, medial pulvinar and lateral pulvinar nuclei, and few fibers from the intralaminar and midline nuclei.
INTRODUCTION It is generally assumed that the anteromedial nucleus projects to the anterior portion of the cingulate cortex, the anteroventral nucleus to the middle and posterior areas of the cingulate cortex, and the anterodorsal nucleus to the posterior cingulate cortex, including the retrosplenial area2,4-6,ta,1a,25,28,al,a2,a4,as. Recently, Niimi et al. 2~, using the Nauta-Gygax and Fink-Heimer methods in the cat, found that the cortical projections of the anterior thalamic nuclei overlap each other more than generally thought. According to them, although the anterior limbic region receives
226 fibers only from the anteromedial nucleus, the cingular area receives fibers from the anteroventral and anteromedial nuclei, and the retrosplenial and postsubicular areas from the anterodorsal, anteroventral and anteromedial nuclei. The present study attempts to confirm these findings using the method of retrograde axonal transport of horseradish peroxidase (HRP) 1'~,14. MATERIAL AND METHODS Fifteen normal adult cats (18 cases) were used in the present study. During sterile surgical procedures, injections of 0.054).1 #1 of a 30% solution of H R P (Sigma VI) in 0.9 ~o sterile saline were made unilaterally or bilaterally into various areas of the limbic cortex, since no evidence for crossed cortical projections of the anterior thalamic nuclei was known. Under Nembutal anesthesia, the animals were placed in a stereotaxic head holder. H R P was injected by one penetration of a 1 #1 Hamilton microsyringe needle held in a microinjection holder mounted on an electrode carrier through a trephined hole in the calvarium. After survival of 48 h, the animals were deeply anesthetized and fixed by transcardiac perfusion with 200 ml
I
i i
IIR,
1
o J "~°" ....
![ '
:
L
,IIIR
, i
/ ]
,,
j
•
:'Pr
Fig. 1. Diagram to show the site and extent of HRP injections drawn on a standardized outline of the right medial cortex in all the cats studied. In this figure cortical injections madein either or both left and right cerebral hemispheres are all depicted onthe right hemisphere to facilitate comparison. The numbers indicate cat numbers. Blackened areas and surrounding white areasindicate lhe central and peripheral areas of the injection sites. Vertical lines represent needle tracks: The banks of sulci are indicated by areas lying close to the sulci. AbbreviatiOns for this and all Subsequent figures are found listed after the Discussion.
227 of 0.1 M phosphate buffer (pH 7.4) containing 10°/o sucrose, followed by 2000 ml of a mixture of 5 ~o formalin-1 ~o glutaraldehyde in the phosphate buffer. The brains were removed from the skull, cut into blocks and immediately transferred to the phosphate buffer containing 30 ~ sucrose, and then stored in the same fluid overnight at 4 °C. Frozen sections through the cortical injection sites and the thalamus were cut at 60 # m thickness in the stereotaxic plane. Sections were collected in 0.1 M phosphate buffer, pH 7.6. After rinsing in the phosphate buffer 3 times, every fourth section was transferred to an incubation medium containing 0.05 ~o 3,3'-diaminobenzidine tetrahydrochloride and 0.01 ~ HzO2 in Tris buffer. The sections were incubated in this medium for 20-30 min at room temperature, transferred through 3 changes of distilled water and mounted on slides with alcoholic gelation. Sections were lightly counterstained with 0.1 ~ cresyl violet in order to determine the exact location of the HRP-labeled cells. The injection sites were reconstructed and indicated on a standardized diagram of the medial cortex of the cerebral hemisphere (Fig. 1). Neurons were interpreted as labeled when they contained the reaction products of H R P in distinct granules with the cell soma and proximal dendrites. The stereotaxic atlas of Reinso-Squ/lrez 29 was used for the stereotaxic injection of H R P into the limbic cortex. However, the limbic cortical areas were defined, for the most part, according to the cytoarchitectural study of Rose and Woolsey 31 in the cat. They divided the limbic cortex into the anterior and posterior limbic regions, of which the latter is composed of the cingular and retrosplenial areas. In addition they defined the postsubicular area, which may be regarded as part of the presubicular area 30. In the present paper, the term presubicular area will be employed in a narrow sense, excluding the postsubicular area. The thalamic nuclei were classified and named following Niimi and Kuwahara 21.
SS~ S
CATIOR
~
SS
CAT21L
Fig. 2. Transverse sections through the cerebral hemisphere to show the maximal extent of HRP injections in cats 10R, 21R, 25R and 21L. Blackened areas and surrounding stippled areas indicate the central and peripheral areas of the injection sites. Broken lines represent needle tracks.
228
I # CAI
,:,,,
Fig. 3. Distribution of HRP-labeled cells (crosses) in the thalamus of cat 9R. Transverse sections, RESULTS
(l) Cases with injection sites lying largely in the anterior timbic region In cats 9R, 14R, and IOR. H R P was injected stereotaxicatly into the anterior limbic region. The injection needle was directed vertically, passing through cortical area 5 and the lips of the cruciate sulcus (including area 6) to reach the anterior limbic region. The injection site in cat 10R was confined largely to area 6 (see ref. 8) and the adjoining portion of the anterior limbic region (Figs. 1 and 2). Numerous labeled cells were found in the ventromedial part of the anteromedial nucleus, whereas only a few cells were labeled in the dorsolateral part (Figs. 3 and 7A). Within the ventromedial part of the anteromedial nucleus, labeled cells increased in number as the injection site was displaced more ventrally (Table !). Occasional cells were labeled in the anterodorsal and anteroventral nuclei. Labeled cells were also detected in the paracentral, medial central, rhomboid and reuniens nuclei (Fig. 3). In cases with injection sites involving area 6, labeled cells were seen in the ventral anterior and ventral lateral nuclei (cats 10R and 14R). Injections in the anterior limbic region adjacent to the granular frontal cortex led to labeling in the dorsomedial, submedial, ventral medial and paratenial nuclei (cat 9R). (II) Cases with injection sites centered in the cingular area In cats l l R , 13R, and 12L, the injection needle passed vertically through the cortex of the suprasplenial and splenial gyri (area 17) and reached the cingular area. The injection sites in cats 11R and 13R were present in the anterior portion of the cingular area, whereas the injection site in cat 12L was in the posterior portion (Fig. 1).
229 A considerable number of labeled cells were seen scattered in the magnocellular part of the anteroventral nucleus. Scarcely any labeled cells were found in the parvocellular part. In cats I l R and 13R, the anteromedial nucleus contained many labeled cells, particularly in the ventromedial part (Fig. 4A). In cat 12L, however, the labeled cells were much more numerous in the dorsolateral part than in the ventromedial part. Labeling in the anterodorsal nucleus was found only in cat 11R. In the dorsal lateral nucleus labeled cells were detected occasionally in cats I IR and 13R, but were numerous in cat 12L where labeling was also found in the medial and lateral pulvinar nuclei. Very few, if any, labeled cells were found in the lateral geniculate nucleus. In cats I 1R and 13R, a fair number of labeled cells were detected in the paracentral nucleus, and occasional labeled cells in the lateral central, ventral anterior, ventral lateral, ventral medial and submedial nuclei. In cats 21R, 25R and 21L, the injection needle passed vertically through the lateral gyrus and the underlying white matter and reached the lower bank (cats 21R and 25R) or fundus (cat 21L) of the splenial sulcus (Figs. 1 and 2). A few cells were labeled in both magnocellular and parvocellular parts of the anteroventral nucleus in cats 21R and 25R (Fig. 4B). In cat 21L labeling was found only in the parvocellular part. In these cats no labeled cells were seen in the anteromedial nucleus. A large number of labeled cells were detected in the dorsal lateral and medial pulvinar nuclei, and some labeled cells in the posterior lateral, lateral pulvinar and ventral anterior nuclei. Only occasional cells were found in the lateral central nucleus, in cat 21L very few cells were labeled in the paracentral, medial central and ventral nuclei.
A
C A T 11R
CA ! 2 5 H
Fig. 4. Distribution of HRP-labeled cells (crosses) in the thalamus of cats 11R (A) and 25R (B). Transverse sections.
230
T,
P1
..-/
CAT 7R
~
m
PC
x
= CM
Fig. 5. Distribution of HRP-labeled cells (crosses) in the thalamus of cat 7R. Transverse sections.
(111) Cases with injection sites largely confined to the retrosplenial area In cats 7L, 19R, 19L. 7R and 18R, HRP was injected into the retrosplenial area. The injection needle passed vertically through the cortex of the suprasplenial and splenial gyri into the anterodorsal part of the retrosptenial area in cats 7L. 19L and 19R, whereas the needle passed through the suprasylvian cortex and the underlying white matter in cats 7R and 18R (Fig. 1). The injection site of cat 18R corresponded to the agranular part of the retrosplenial area (area 30 of Brodmann3). In cats 7L, 19R, 19L and 7R. a large number of labeled cells were concentrated in the anterodorsal nucleus and the magnocellular part of the anteroventral nucleus (Figs. 5 and 7C). Numerous labeled cells were also found in both dorsolateral and ventromedial parts of the anteromedial nucleus (Fig. 7B). The parvocellutar part of the anteroventral nucleus contained only occasional labeled cells, which may have resulted from a slight leakage of H R P along the injection needle passing through the lower lip of the splenial sulcus. It should be noted that a large number of labeled cells were detected in the dorsal lateral nucleus, particularly its dorsal portion, and a lesser number in the most dorsal parts of the medial and lateral pulvinar nuclei (Fig. 5). No labeling of cells was found in the posterior lateral nucleus. Occasional cells were labeled in the intralaminar and midline nuclei. In addition, few labeled cells were encountered in the ventral anterior, ventral medial and submedial nuclei in cats 19R and 19L (Table 1). In cat 18R no labeling was seen in the anterior nuclei, except for very few cells in the parvocellular part of the anteroventrat nucleus. A large number of labeled cells were found in the dorsal portions of the dorsal lateral and medial pulvinar nuclei, and less numerous cells were labeled in the most dorsal part of the lateral pulvinar nucleus.
231
(IV) Cases with injection sites in the postsubicular and presubicular areas In cats 6R, 8R, 4R and 20L, H R P was injected into the postsubicular and presubicular areas. The injection needle passed vertically through the cortex of the middle suprasylvian gyrus and the underlying white matter. The injection sites in cats 6R, 8R and 4R involved both postsubicular and presubicular areas, but the injection site in cat 20L was present in the anterodorsal portion of the presubiculum, extending dorsally beyond the limit of the presubiculum (Fig. 1). In cats 6R and 8R, numerous labeled cells were distributed in the anterodorsal and anteroventral nuclei, and some labeled cells were found in the anteromedial nucleus, particularly its ventromedial part (Figs. 6A and 7D). It should be mentioned that the anteroventral nucleus contained labeled cells in both magnocellular and parvocellular parts. A large number of labeled cells were concentrated in the dorsal part of the dorsal lateral nucleus and the most dorsal portion of the medial pulvinar nucleus, and some cells were labeled at the dorsal periphery of the lateral pulvinar nucleus. In addition, occasional labeled cells were seen in the paracentral, lateral central and midline nuclei. In cat 4R very few labeled cells were detected in the anterior nuclei, but abundant cells were labeled in the dorsal part of the dorsal lateral nucleus and the dorsal periphery of the medial and lateral pulvinar nuclei. In cat 20L more labeled cells were found in the anterodorsal and anteroventral nuclei, although no labeling was seen in other thalamic nuclei, except for the dorsal lateral and reuniens nuclei (Fig. 6B). DISCUSSION
(I) Anterior limbic region Our results reveal that the anterior limbic region receives fibers largely from the
A
B
CAT6R
CAT 20L
Fig. 6. Distribution of HRP-labeled cells (crosses) in the thalamus of cats 6R (A) and 20L (B). Transverse sections.
233 anteromedial nucleus and partly from the anterodorsal and anteroventral nuclei (cats 9R, 14R and 10R). The labeled cells in the ventromedial part of the anteromedial nucleus increase in number with the ventral displacement of the injection site (Table I). This appears to indicate a dorsoventral organization of the cortical projections of the anteromedial nucleus to the anterior limbic region, confirming the study of Niimi et al. ~ using the Nauta method. A considerable number of labeled cells were found in the dorsomediak submedial and ventral medial nuclei, in addition to the anteromedial nucleus following HRP injection into the anteroventral portion of the anterior limbic region (cat 9R). This indicates that there is considerable overlap of the projection areas of the anteromedial nucleus and the dorsomedial, submedial and ventral medial nuclei which were all reported to send fibers to the granular frontal cortex (Niimi et al.~4). Beckstead ~ stated that the respective thalamocortical projections of the dorsomedial and anteromedial nuclei overlap over a wide region of the anterior medial cortex in the rat. In cat 9R a few labeled cells were seen in the paratenial nucleus. According to Niimi et al. (unpublished data), some cells in this nucleus were labeled following injections of HRP in the frontal granular cortex.
(ll) Cingular area According to the present study, the cingular area receives a major input from the anteroventral and anteromedial nuclei (cats l lR, 13R and 12L). The results obtained with the Nauta silver technique (Niimi et al. 26) revealed that the projection of the anteroventral nucleus overlaps that of the anteromedial nucleus in the cingular area. Krieg 1l and Meyer et al. is described the projection of the anteromedial nucleus to the posterior part of the cingular cortex. HRP injection into the more ventral portion in the cingular area tended to result in labeling of cells in the more medial portion of the anteroventral nucleus (cat 7L). This may indicate a mediolateral organization of the cortical projections of the anteroventral nucleus, as suggested by Domesick 6 in the rat. The Nauta study of Niimi et al. 2~ suggests a mediolateral and anteroposterior organization of the cortical projections of the anteroventral nucleus. Our results indicated that injections of HRP into the lower bank and fundus of the splenial sulcus lead to cell labeling in the parvocellular part of the anteroventral nucleus, in addition to the magnocellular part (cats 21 L, 21R and 25R). The projections of the parvocellular part of the anteroventral nucleus to the lower bank of the splenial sulcus were suggested by Niimi and Sprague '~2 using the method of retrograde cell degeneration and later confirmed by Niimi et al. 26 with the use of the Nauta method. (lll) Retrosplenial, postsubicular and presubicular areas Our results reveal that the retrosplenial area receives fibers from the anterodorsal, anteroventral and anteromedial nuclei (cats 7L, 19R, 19L and 7R). In most of these cases, very few labeled cells were found in the parvocellular part of the anteroventral nucleus, but this may be due to the involvement of the lower lip of the splenial sulcus in the injected area (Table 1). According to the Nauta study of Niimi
234
t
ill
u~tlll qi
I iil ©
I .u i
i
f
~m/
i i
III
~if:
-H -i! I i~
~-HI
I L
I11
li~!t
III
I J ,H
-!i-
[I
d
i ~i ~ H i t
I
J 1 ~J
ii
I L
J ~! J
t
©
E
I I H ~-H
it
I
I -h
fi
~L ~
~i i ¸
f i
.,c
I
--
_o
B~
:,3
=~
235 et al. 26, the cortical projections of the anterodorsal, anteroventral and anteromedial nuclei overlap in the retrosplenial area. Domesick 6 stated that the anteromedial nucleus projects to the anterior limbic region and presubiculum but sends no fibers to the retrosplenial area. Our results indicate that scarcely any labeled cells were present in the anterior thalamic nuclei following HRP injection into the agranular retrosplenial area (cat 18R), confirming the results of Niimi et al. 26 using the Nauta method. Niimi (unpublished data) found terminal degeneration in the postsubicular and presubicular areas following lesions in the anterodorsal, anteroventral and anteromedial nuclei, in essential agreement with the results of Domesick 5,6 in the rat. Our data also demonstrated that injections of H R P into these areas resulted in labeling of cells particularly in these anterior nuclei, of which the anteroventral nucleus contained labeled cells in both magnocellular and parvocellular parts (cats 6R, 8R, 4R and 20L). Within the dorsal lateral nucleus, labeled cells appeared in all cases with injection sites in the limbic cortex, except for the anterior limbic region (Table I). The labeled cells were most numerous following injections of HRP into the retrosplenial, postsubicular and presubicular areas and the cortex within the splenial sulcus. The projections of the dorsal lateral nucleus to the cingular and suprasylvian cortices have been demonstrated by the degeneration methods 16,17,e°. In our cases with injection sites in and near the fundus of the splenial sulcus (area 19 of Otsuka and Hassler27), labeled cells appeared in the posterior lateral nucleus (cats 21L and 25R). Niimi and lnoshita 2° stated that the posterior lateral nucleus projects heavily to the banks and bottom of the splenial sulcus, in addition to the suprasylvian and lateral gyri. According to our results, labeled cells were detected in the medial and lateral pulvinar nuclei following injections of HRP in the postsubicular and presubicular areas and in the middle and posterior parts of the retrosplenial and cingular areas, including the lower bank and fundus of the splenial sulcus (Table D. It should be noted that labeled cells were seen scattered throughout the medial and lateral pulvinar nuclei following injections of HRP into the lower bank and fundus of the splenial sulcus, while these were concentrated in the most dorsal parts of these nuclei following H R P injection into the retrosplenial, postsubicular and presubicular areas. It has been demonstrated by the Nauta method that the lateral pulvinar nucleus sends fibers to the suprasylvian cortex and the cortex within the splenial sulcus 7,23. The possibility that some of the labeled cells in the lateral pulvinar and dorsal lateral nuclei may have resulted from the leakage of HRP along the injection needle cannot be ruled out, since the needle passed vertically through the middle suprasylvian gyrus in cats 7R, 18R, 6R, 8R, 4R and 20L. In most of our cases labeled cells were seen scattered in the paracentral and lateral central nuclei. Within the rhomboid, medial central and reuniens nuclei, a few labeled cells were encountered in many cases (Table I). Jones and Leavitt 9, using the HRP method, demonstrated that the intralaminar nuclei project sparsely and diffusely upon the cerebral cortex. There has yet been no detailed account of the cortical projections of the midline thalamic nuclei.
236 A lair n u m b e r o f labeled cells were f o u n d in the ventral a n t e r i o r a n d ventral lateral nuclei following injections into a r e a 6 a n d n e i g h b o r i n g areas (cats 10R, 14R, I I R and 13R). it has been d e m o n s t r a t e d that these nuclei project to areas 4 and 6 a n d to areas 5 and 7 (see refs. 10 a n d 19). In cats 9R, 14R a n d 10R, the injection needle passed t h r o u g h cortical a r e a 5 and the underlying white matter, but in cat 9R no labeling was f o u n d in the ventral a n t e r i o r a n d ventral lateral nuclei. The injection needle p a s s e d vertically t h r o u g h the lateral, s u p r a s p l e n i a l and splenial gyri (area 17) in cats I1R, 13R, 21R, 21L, 25R, 12L, 7L, 19R and 19L. H o w e v e r very few, if any, labeled cells were detected in the lateral geniculate nucleus, Since the injection needle passed vertically t h r o u g h the cortex o f the medial surface o f the hemisphere in m a n y cases, d a m a g e to the cingulum by the injection needle a p p e a r e d to be only slight, in cats 7R, 18R, 6R, 8R, 4 R a n d 20L, the needle traversed the cingulum but was located too c a u d a l l y to involve m a n y fibers o f passage in the cingulum. ABBREVIATIONS AD AMD. AMV AV AVM AVP CD Cg CL CM LA LD LP
= : : =
anterodorsal nucleus dorsolateral part of anteromedial nucleus ventromedial part of anteromedial nucleus anteroventral nucleus magnocellular part of anteroventral nucleus parvocellular part of anteroventral nucleus dorsal central nucleus cingular area lateral central nucleus medial central nucleus anterior timbic region dorsal lateral nucleus posterior lateral nucleus
MD Pc PL PM Pr Ps Pt R Rh Rs Rt SC Sm SS VA VL VM
dorsomedial nucleus paracentral nucleus lateral pulvinar nucleus medial pulvinar nucleus presubicular area postsubicular area paratenial nucleus reuniens nucleus rhomboid nucleus . retrosplenial area thalamic reticular nucleus cruciate sulcus submedial nucleus splenial sulcus ventral anterior nucleus ventral lateral nucleus ventral medial nucleus
ACKNOWLEDGEMENTS W e wish to express o u r g r a t i t u d e to Professor J a m e s M. Sprague, D e p a r t m e n t o f A n a t o m y , University o f Pennsylvania, for his helpful suggestions in the p r e p a r a tion o f this paper.
REFERENCES 1 Beckstead, R. M.,Convergent thatamicandmesencephalicprojectionstotheanterior medialcortex in the rat, J. eomp. NeuroL, t66 (1976) 403-416. 2 Bodian, D., Studies on the diencephalon of the Virginia opossum. Part I11. The thalamo-cortical projection, J. comp. NeuroL, 77 0942) 525-575. 3 Brodmann, K., Vergleiehende Lokalisationslehre der Grosshirnrinde, Barth,: Leipzig, 1909. 4 Clark, W. E. Le Gros and Boggon, R. H., On the connexions of the anterior nucieus of the thalamus, J. Anat. (Lond.), 67 (1933) 215-226. 5 Domesick, V. B., The fascieulus einguli in the rat, Brain Research, 12 (1970) 19-32.
237 6 Domesick, V. B., Thalamic relationships of the medial cortex in the rat, Brain Behav. Evol., 6 (1972) 457-487. 7 Graybiel, A. M., Some ascending connections of the pulvinar and nucleus lateralis posterior of the thalamus in the cat, Brain Research, 44 (1972) 99 125. 8 Hassler, R. und Muhs-Clement, K., Architektonischer AuPoau des sensomotorischen und parietalen Cortex der Katze, J. Hirnforsch., 6 (1964) 377-420. 9 Jones, E. G. and Leavitt, R. Y., Retrograde axona[ transport and the demonstration of nonspecific projections to the cerebral cortex and striatum from thalamic intralaminar nuclei in the rat, cat and monkey, J. comp. NeuroL, 154 (1974) 349-378. 10 Kobayashi, E. and Niimi, K., Cortical projections of the anterior and lateral ventral nuclei in the cat, Acta anat. Nippon, 48 (1973) 62-63. I1 Krieg, W. J. S., Connections of the cerebral cortex. 1. The albino rat. C. Extrinsic connections, J. comp. Neurol., 86 (1947) 267 394. 12 Kristensson, K. and Olsson,Y., Retrograde axonal transport of protein, Braht Research, 29 (1971) 363-365. 13 Lashley, K. S., Thalamo-cortical connections of the rat's brain, J. comp. Neurol., 75 (1941) 67-121. 14 LaVail, J. H. and LaVail, M. M., Retrograde axonal transport in the central nervous system, Science, 176 (1972) 1416-1417. 15 Lewis, P. R. and Shute, C. C. D., The cholinergic limbic system: projections to hippocampal formation, medial cortex, nuclei of the ascending cholinergic reticular system, and the subformical organ and supra-optic crest, Brain, 90 (1967) 521-540. 16 Locke, S., Angevine, J. B. Jr. and Yakovlev, P. I., Limbic nuclei of thalamus and connections of limbic cortex. 1I. Thalamo-cortical projection of the lateral dorsal nucleus in man, Arch. Neurol. (Chic.), 4 (1961) 355-364. 17 Locke, S., Angevine, J. B. Jr. and Yakovlev, P. 1., Limbic nuclei of thalamus and connections of limbic cortex. VI. Thalamo-cortical projection of lateral dorsal nucleus in cat and monkey, Arch. Neurol. (Chic.), 11 (1964) 1-12. 18 Meyer, A., Beck, E. and McLardy, T., Prefrontal leucotomy: a neuroanatomical report, Brain, 70 (1947) 1849. 19 Mizuno, N., Konishi, A., Sato, M., Kawaguchi, S., Yamamoto, T., Kawamura, S. and Yamawaki, M., Thalamic afferents to the rostral portions of the middle suprasylvian gyrus in the cat, Exp. Neurol., 48 (1975) 79-87. 20 Niimi, K. and lnoshita, H., Cortical projections of the lateral thalamic nuclei in the cat, Proc. jap. Acad., 47 (1971) 664-669. 21 Niimi, K. and Kuwahara, E., The dorsal thalamus of the cat and comparison with monkey and man, J. Hirtforsch., 14 (1973) 303 326. 22 Niimi, K. and Sprague, J. M., Thalamo-cortical organization of the visual system in the cat, J. comp. Neurol., 138 (1970) 219-250. 23 Niimi, K., Kadota, M. and Matsushita, Y., Cortical projections of the pulvinar nuclear group of the thalamus in the cat, Brain Behav. Evol., 9 (1974) 422 457. 24 Niimi, K., Matsushita, Y., Matsuoka, H. and Okada, Y., Cortical projections of the submedial and medial ventral nuclei of the thalamus in the cat, Anat. Ree., 187 (1977) 774. 25 Niimi, K., Nakano, T., Koizuka, M. and Ichinona, M., Experimental-anatomical studies on the cortical connections of the anterior thalamic nuclei in carnivores, Okajimas Folia anat. jap., 38 (1962) 95-127. 26 Niimi, K., Niimi, M. and Kawamura, S., Cortical projections of the anterior thalamic nuclei in the cat. In Proe. Xth Int. Congr. Anatomists, Tokyo, 1975, p. 193. 27 Otsuka, R. und Hassler, R., Ueber AuPoau und Gliederung der corticalen Sehsph~ire bei der Katze, Arch. Paychiat. Nervenkr., 203 (1962) 212-234. 28 Pribram, K. H. and Fulton, J. F., An experimental critique of the effects of anterior cingulate ablations in monkey, Brain, 77 (1954) 34-44. 29 Reinso-Squ~.rez, R., Topographischer Hirnatlas der Katze fiir Experimental-Physiologische Untersuchungen, Merck, Darmstadt, 1961. 30 Rose, M., Cytoarchitektonischer Atlas der Grosshirnrinde des Kaninchens, J. Psychol. Neurol. (Lpz.), 43 (1931) 353~440. 31 Rose, J. E. and Woolsey, C. N., Structure and relations of limbic cortex and anterior thalamic nuclei in rabbit and cat, J. comp. NeuroL, 89 (1948) 279 348. 32 Stoffels, J., La projection des noyaux ant6rieurs du thalamus sur l'6corce interh6misph6rique; 6tude anatomo-exp6rimentale, J. belge Neurol. Psychiat., 39 (1939) 743-776, 783-833.
238 33 Walker, A. E., An experimental study of the thalamo-cortical projection of the macaque monkey, J. comp. Neurol., 64 (1936) 1--39. 34 Waller, W. H., Topographical relations of cortical lesions to thalamic nuclei in the albino rat, J. comp. Neurol., 60 (1934) 237 270. 35 Yakovlev, P. l., Locke, S., Koskoff, D. Y. and Patton, R. A., Limbic nuclei of thalamus and connections of limbic cortex: I. Organization of the projections of the anterior group of nuclei and of the midline nuclei of the thalamus to the anterior cingulate gyrus and hippucampal rudiment in the monkey, Arch. Neurol. (Chic.), 3 (1960) 620-641.
