Original Paper Acta Anat 1992;143:246-252
Departamento de Morfología. Facultad de Medicina, Universidad Autónoma de Madrid. España
Key Words Cytochrome oxidase Acetylcholinesterase Globus pallidus Basal ganglia Rat
Some Observations upon the Distribution of Cytochrome Oxidase Activity in the Globus pallidus of the Rat
Abstract The histochemical distribution of the enzyme cytochrome oxidase (CO) was explored in the globus pallidus (GP) of the rat. and it was compared with the dis tribution of acetylcholinesterase (AChE), another well-known enzyme of the basal ganglia in mammals. This neurochemical research illustrates two promi nent findings. In the first place, a regional compartmentalization was detected in the pallidal distribution of CO, in which dorsal territories of the GP exhibited a more abundant presence of this enzyme. In addition, the distribution of this mitochondrial enzyme was not uniform all over those dorsal pallidal territories. Thus, the pallidal concentration of CO was gradually decreasing dorsoventrally and lateromedially, and, sometimes, areas highly stained for CO were intermin gled with zones in which this enzyme was less conspicuous. In the second place, the pallidal distribution of AChE was the opposite of that found for CO (i.e. more abundant in ventral and medial territories of the GP). The functional sig nificance of these findings is discussed in the light of the heterogeneous hodological neuroanatomy of the GP of rodents.
Introduction The globus pallidus (GP) in rodents is a very noticeable part of the corpus striatum. It is located medially and ventrally to the major component of this structure, the striatum itself. The latter is the main origin of projections to the GP [1-5] that, in turn, projects principally to the subthalamic nucleus [6,7], and also to the substantia nigra [8-12], and to the entopcduncular nucleus [13J. In addition, a projection to the striatum [10, 14] and to the cerebral cortex [15] has been reported in rodents. Furthermore, it has also been demonstrated consistently in the rat and in the cat that the
Received: October 8. 1991 Accepted: November 7. 1991
GP projects outside the basal ganglia to the thalamus [15-17] and, particularly, to the reticular thalamic nucleus [ 18—211. Interestingly, this pallidal projection to the retic ular thalamic nucleus has also been described very recently in the primate [22], confirming the results obtained by Hassler [23] and Yumamoto et al. [24], Thus, this long-view intrinsic nucleus of the basal ganglia seems to reach a posi tion among the output nuclei of these basal structures of the brain [25], and. perhaps, playing a crucial role, since the reticular thalamic nucleus might control a wide plurality of thalamocortical and corticothalamic connectivity [22. 25-27],
Dr. J.M. Giménez-A maya Departamento de Morfología. Facultad de Medicina Universidad Autónoma de Madrid CVArzobispo Morcillo S/N, E-28029 Madrid (Spain)
© 1992 Karger AG. Bascl 0001-5180/92/1433-0246 $ 2.75A)
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J.M. Giménez-Amaya
Material and Methods Several rats (Sprague-Dawlcy) were available for this study. A complete description of the anesthetic protocols, perfusion solutions and histochemical processing is available in a previous report [30]. At least, two series in each case were processed adjacently (or close enough to each other) both for CO and for AChE. To reveal the CO activity, we strictly followed the protocol described at great length by Wong-Riley [40]. AChE staining was carried out by a method slightly modified from that of Geneser-Jcnscn and Blackstad [41, 42].
Results The more striking findings of this study are of two sorts. First, we detected a regional as well as a more local compartmentalization in the distribution of CO within the GP. Second, the pallidal localization of CO was not in register with the pallidal distribution of AChE. Figures 1-3 were prepared to illustrate, in a rostrocaudal sequence, the palli dal distribution of CO and, additionally, to compare it with the anatomical localization of AChE within the medial and ventral part of the corpus striatum. Thus, six sections stained for CO were processed together with another set of sections stained for AChE 80 pm apart each from its com panion. In general, the most abundant concentration of pallidal CO was in the most dorsal and lateral parts of the GP close to the internal capsule and to the striatum itself (fig. 1-3). By contrast, ventral pallidal territories, still in the so-called dorsal pallidum [20,43] and the ventral pallidum of Heimer
and Wilson [44], were more weakly stained for CO (fig. 1-3). AChE, however, was found to be higher in those territories just mentioned, and many cells very prominently stained for AChE were detected precisely in those ventral areas of the GP in its middle and caudal thirds (fig. 2b', 3). In addition, the CO was distributed heterogeneously all through the rostrocaudal extension of the GP but in its very rostral pole, whereas the pallidal distribution of AChE was more homogeneous and mainly confined to its caudal half. Moreover, for the CO histochemistry the neuropil was more abundant than the cells, although the variations between neuropil and cells all through the rostrocaudal extension of the GP were not explored in this neuroanatomical study. The very rostral pole of the GP was weakly stained for CO, and, further, it was not feasible to detect any sign of clear heterogeneity in the distribution of this enzyme (fig. la). AChE was also very weak at those pallidal levels (fig. la). More caudal territories in this rostral third of the GP (fig. lb) as well as in its middle and caudal thirds (fig. 2, 3) presented a clear regional design in the histo chemical localization of CO, and such a distribution was very much the opposite of that found for the pallidal locali zation of AChE (fig. lb. b'; fig.2, 3). Thus, dorsal territo ries of the pallidum in its rostral third and dorsal and lateral portions of its middle and caudal thirds presented the high est concentration of pallidal CO. More ventral territories in its rostral third and more ventral and medial parts of its middle and caudal thirds presented a weaker staining for CO. In sharp contrast, however, these pallidal areas just mentioned were highly stained for AChE. This fact was remarkably observed in the rostral part of the middle third of the GP (fig.2a, a') for the dorsoventral histochemical segregation between CO and AChE, and in the caudal part of the middle pallidal third (fig.2b, b') and all through the caudal third (fig.3), for the dorsolateral/ventromedial histochemical segregation of these pallidal markers. The caudal pallidal half in which the most medial territories of the pallidum were more weakly stained for CO was particu larly noticeable for the presence of a great number of large cells highly stained for AChE, very likely corresponding to the large cholinergic cells of the basal nucleus of Meynert (fig.2b'. 3a'. b') [45], Finally, the middle third of the GP was the place in which it was more feasible to detect a more local heteroge neity in the anatomical distribution of CO (see areas of the GP showed by arrows in fig.2a, b). Thus, areas with a higher concentration of CO were sometimes intermingled with areas with a smaller amount of this mitochondrial enzyme.
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To study the histochemical composition of the GP. therefore, may provide us with an interesting neuroanatomical knowledge to better understand the functionality involved in its connectivity within the different basal gan glia circuits. Since a heterogeneous distribution of the mito chondrial enzyme cytochrome oxidase (CO) has been described in the rat's striatum [28-30]. we thought it of interest to explore its distribution in the GP of the same animal and to compare it with the distribution of acetylcho linesterase (AChE), another well-known enzyme of the mammalian basal ganglia. The results described here point to consider the GP of rodents as a heterogeneous structure in which the distribution of CO may follow a regional and a more local compartmental design. It might also account for functional differences regarding its direct hodological rela tionship with other nuclei within the basal ganglia as well as with the thalamus either directly or through the reticular thalamic nucleus [22. 31-39],
a
Fig. 1. Coronal sections through the ros tral GP of the rat’s brain, a. b Distribution of pallidal CO. and those sections are accompa nied respectively by a pair of sections pro cessed for AChE 80 pm apart (a', b'). The rostral pole was stained weakly for CO as well as for AChE (a. a ). A more compartmental distribution of these histochcmical pallidal markers was present in more posterior levels of the rostral pallidal third (arrows in b and b'). Asterisks point to corresponding blood vessels. AC = Anterior commissure; BST = bed nucleus of the stria terminalis; CP = caudate-putamcn complex; FS = fundus striati; IC = internal capsule; SI = substantia innominata of Reichter: VP = ventral palli dum. Scale bar (also for fig.2. 3)=0.3 mm.
Stated briefly, this histochcmical report is in good agree ment with the notion of the rat’s GP to be a heterogeneous structure within the basal ganglia. These results, together with those neuroanatomical studies that show its hodological relationship with a wide variety of prosencephalic and
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mesencephalic structures (see Introduction for references), point to consider the GP as another crucial structure in the processing of information within the basal ganglia of rodents [22. 25-27). In order to offer an adequate interpretation of the results showed in this study, however, a note on method ology should be made. Thus, as pointed out in a previous
Pallidal Distribution of Cytochrome Oxidase
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Discussion
a
a
Fig. 2. Coronal sections through the middle GP in the rostrocaudal coordinates of the rat's brain, a. b Localization of pallidal CO. a', b' Pallidal distribution of AChE in close sections to a and b, respectively. Note the dorsoventral (a. a') and the dorsolateral/ ventromedial (b. b') histochemical segrega tion of these pallidal markers. Arrows point to areas with a more local compartmentalization in the GP. in which areas with lower staining for CO were intermingled with oth ers more highly stained. Asterisks point to corresponding blood vessels. CP = Caudateputamen complex: IC = internal capsule; SI = substantia innominata of Reichter; VP = ventral pallidum.
the histochemical parcelation of the GP is very sensitive and, perhaps, highly specific in its functional regulation and expression [30], The same can be said for the tissular distri bution of the enzyme AChE within the GP of rodents. The results offered here show that the GP in the rat is another heterogeneous histochemical structure of the basal ganglia. And since the GP is also very heterogeneous from
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paper [30], it seems conceivable that different histochem ical procedures can induce different pallidal distributions of CO. as it is the case for the striatum [28-30], It might actu ally reflect the fact that the activation of this transmem brane protein of the inner mitochondrial membrane [29] could be made differently according to the experimental methodology used. And further, it would also suggest that
Fig. 3. Coronal sections through the cau dal GP of the rat's brain, a. b Localization of CO. a', b' Distribution of AChE. A clear dorsolateral/vcntromedial compartmental design was visible in this caudal third of the GP. Asterisks point to corresponding blood vessels. B = Nucleus basalis of Meynert; CP=caudate-putamen complex; IC = inter nal capsule; Sl=substantia innominata of Rcichter; Th = thalamus.
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GP (fig. 1-3). and the striatum sends its pallidal connec tions, at least for the rostral striatal territories, in a topo graphical fashion [2,3, 5]. As mentioned before (see Intro duction). the GP. in turn, connects mainly with the subtha lamic nucleus, and also with the substantia nigra, entopeduncular nucleus, striatum, cortex and thalamus, particu larly with the reticular thalamic nucleus. The GP, there
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the hodological point of view [3. 5. 25. 27. 36. 37, 39, 46-48], a new anatomical vision upon its functionality is beginning to emerge [see, for instance, fig.3 in ref.25 and fig. 3 in ref.22], The GP receives its main afferentation from the stria tum, the largest part of the corpus striatum [see ref.5 and references therein]. This structure is in close vicinity to the
fore, receives an important neural information from the striatum that is the first step in the cortical realm of the basal ganglia. The GP. in turn, might transfer that informa tion into different hodological loops within the basal gan glia nuclei (item: GP—» subthalamic nucleus—» entopeduncular nucleus —» GP; item: GP —» substantia nigra pars compacta —» striatum —» GP; item: GP —» striatum —» GP; item: GP —» cortex —» striatum —» GP). Furthermore, the GP might also convey this incoming striatal information outside the basal ganglia, by means of its thalamic relation ship. All this ncuroanatomical data place the GP in the mid dle of very complex circuitous routes in the forebrain of mammals [25-27, 33, 36, 43]. Not only does it appear to start a thalamic realm indirectly through the subthalamic and the endopeduncular nuclei [34], and directly through its thalamic connectivity, particularly with the reticular tha lamic nucleus, but also it may induce feedback regulatory loops regarding its afferentation (e.g. the nigrostriatal dopaminergic projection) [9] and that of the basal ganglia themselves as a whole (e.g. pallidal innervation of the cer ebral cortex) [15]. The fact that it also presents a highly spe cific and heterogeneous distribution of tissular enzymes (e.g. CO and AChE) emphasizes the hypothesis of its role as a crucial step for highly organized neural tasks within the basal ganglia of mammals [25-27].
Obviously, the next step to be taken experimentally in order to better understand the form and function of the GP is to correlate accurately in the same animal the afferent and efferent projections to this structure with the precise distribution of pallidal CO and AChE. This study is pres ently under way, and preliminary results show that, at least for the rostral striatopallidal pathway, dorsal territories in the striatum which present a high concentration of CO innervate the CO recipient of the globus pallidus in the rat [5, 30]. More detailed studies are necessary, however, to correlate hodologically these striatal and pallidal distribu tions of CO, since it is not yet clear whether the gradual decrease in CO within the pallidum corresponds to a regional variation in the distribution of CO within the stria tum and whether the striosomal distribution of CO in the striatum has a correspondence with the more local hetero geneity detected in the GP of the rat [29, 30, 42. 49],
Acknowledgements The author expresses his sincere appreciation to Prof. J.L. Velayos and E. Mengual for their most valuable comments and criticisms, and to J. Hernandez-Claumarchirant, P. Romero and R. Sdnchez-Lozano for their technical assistance in the histochcmical preparations. This study was supported by CICYT grant PB88-0170.
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39 GimtSnez-Amaya, J.M.; Graybiel. A.M.: Modular organization of projection neurons in the matrix-compartment of the primate stria tum. .1. Neurosci. 11: 779-791 (1991). 40 Wong-Rilcy. M.: Changes in the visual system of monocularly sutured or enucleated cats demonstrable with cytochrome oxidase histo chemistry. Brain Res. 171: 11-28 (1978). 41 Gencser-Jenscn. F.A.; Blackstad. J.W.: Dis tribution of acetylcholinesterase in the hippo campal region of the guinea pig. Z. Zellforsch. mikrosk. Anal. 114: 460-481 (1971). 42 Graybiel, A.M.: Ragsdale. C.W.. Jr.: Histochemically distinct compartments in the stria tum of human, monkey, and cat demonstrated by acetylcholinesterase staining. Proc. natl. Acad. Sci. USA 75: 5723-5726 (1978). 43 Nauta. W.J.I L: Circuitous connections linking cerebral cortex, limbic system, and corpus striatumtin Doane. Livingston. The limbic sys tem: functional organization and clinical disor ders. pp. 43-54 (Raven Press. New York 1986). 44 Heinter. L.: Wilson. R.D.: The subcortical projections of the allocortex: similarities in the neural associations of the hippocampus, the piriform cortex, and the neocortex: in Santini. Golgi centennial symposium, pp. 177-193 (Raven Press. New York 1975). 45 Paxiaos. G.; Watson. C .: The rat brain in ste reotaxic coordinates (Academic Press. North Ryde 1986). 46 Parent. A.: Comparative neurobiology of the basal ganglia (Wiley & Sons. New York 1986). 47 Parent. A.: Extrinsic connections of the basal ganglia. Trends Neurosci. 13: 254-258 (1990). 48 Setemon. L.D.; Goldman-Rakic. P.S.: Topo graphic intermingling of striatonigral and striatopallidal neurons in the rhesus monkey. J. comp. Neurol. 297: 359-376 (1990). 49 Graybiel. A.M.: Neurotransmiltcr and neuromodulators in the basal ganglia. Trends Neu rosci. 13: 244-254 (1990).
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16 Severin. C.M.; Young. P.A.: Massopust. L.C.: Pallidothalamic projections in the rat. J. comp. Neurol. 166: 491-502 (1976). 17 Sugimoto. T.; Hattori. T.: Direct projections from the globus pallidus to the paraventricular nucleus of the thalamus in the rat. Brain Res. 323: 188-192 (1984). 18 Carter. D.A.: Fibiger. H.C.: The projections of the entopeduneular nucleus and globus palli dus in rat as demonstrated by autoradiography and horseradish peroxidase histochemistry. J. comp. Neurol. 177: 113-124 (1978). 19 Nauta. H.J.W .: Projections of the pallidal complex: an autoradiographic study in the cat. Neuroscience 4: 1853-1873 (1979). 20 Haber, S.N.: Groenewegen. H.J.: Grove. E.A.: Nauta. W .J.H.: Efferent connections of the ventral pallidum: evidence of a dual striatopallidofugal pathway. J. comp. Neurol. 235: 322-335 (1985). 21 Cornwall. J.; Cooper. J.D .: Phillipson. O.T.: Projections to the rostral reticular thalamic nucleus in the rat. Exp. Brain Res. 80: 157-171 (1990). 22 Hazrati. L.N.: Parent. A.: Projection from the external pallidum to the reticular thalamic nucleus in the squirrel monkey. Brain Res. 550: 142-146 (1991). 23 Hassler. R.: Über die Rinden- und Stammhirnanteilc des menschlichen Thalamus. Psych iatrie Neurol. med. Psychol. /: 181-187 (1949). 24 Yumamoto. T.: Hassler. R.: Huber. C.: Wag ner. A.: Sasaki. K.: Electrophysiologic studies on the pallido- and cerebellothalamic projec tions in squirrel monkey (Saimirí scitireus). Exp. Brain Res. 51: 77-87 (1983). 25 Giménez-Amaya. J.M.: The association cortex and the basal ganglia: a neuroanatomical view upon their relationship based on hodological studies. J. Hirnforsch. 32: 501-510 (1991). 26 Nauta. H.J.W .: A simplified perspective on the basal ganglia and their relation to the limbic system; in Doane. Livingston. The limbic sys tem: functional organization and clinical disor ders. pp. 67-77 (Raven Press. New York 1986). 27 Giménez-Amaya. J.M .: Una visión neuroanatómica de los ganglios basales con algunas implicaciones en su fisiopatologfa. Rev. Med. Univ. Navarra XXXVI: 19-24 (1991).
Departamento de Morfología. Facultad de Medicina, Universidad Autónoma de Madrid. España
Key Words Cytochrome oxidase Acetylcholinesterase Globus pallidus Basal ganglia Rat
Some Observations upon the Distribution of Cytochrome Oxidase Activity in the Globus pallidus of the Rat
Abstract The histochemical distribution of the enzyme cytochrome oxidase (CO) was explored in the globus pallidus (GP) of the rat. and it was compared with the dis tribution of acetylcholinesterase (AChE), another well-known enzyme of the basal ganglia in mammals. This neurochemical research illustrates two promi nent findings. In the first place, a regional compartmentalization was detected in the pallidal distribution of CO, in which dorsal territories of the GP exhibited a more abundant presence of this enzyme. In addition, the distribution of this mitochondrial enzyme was not uniform all over those dorsal pallidal territories. Thus, the pallidal concentration of CO was gradually decreasing dorsoventrally and lateromedially, and, sometimes, areas highly stained for CO were intermin gled with zones in which this enzyme was less conspicuous. In the second place, the pallidal distribution of AChE was the opposite of that found for CO (i.e. more abundant in ventral and medial territories of the GP). The functional sig nificance of these findings is discussed in the light of the heterogeneous hodological neuroanatomy of the GP of rodents.
Introduction The globus pallidus (GP) in rodents is a very noticeable part of the corpus striatum. It is located medially and ventrally to the major component of this structure, the striatum itself. The latter is the main origin of projections to the GP [1-5] that, in turn, projects principally to the subthalamic nucleus [6,7], and also to the substantia nigra [8-12], and to the entopcduncular nucleus [13J. In addition, a projection to the striatum [10, 14] and to the cerebral cortex [15] has been reported in rodents. Furthermore, it has also been demonstrated consistently in the rat and in the cat that the
Received: October 8. 1991 Accepted: November 7. 1991
GP projects outside the basal ganglia to the thalamus [15-17] and, particularly, to the reticular thalamic nucleus [ 18—211. Interestingly, this pallidal projection to the retic ular thalamic nucleus has also been described very recently in the primate [22], confirming the results obtained by Hassler [23] and Yumamoto et al. [24], Thus, this long-view intrinsic nucleus of the basal ganglia seems to reach a posi tion among the output nuclei of these basal structures of the brain [25], and. perhaps, playing a crucial role, since the reticular thalamic nucleus might control a wide plurality of thalamocortical and corticothalamic connectivity [22. 25-27],
Dr. J.M. Giménez-A maya Departamento de Morfología. Facultad de Medicina Universidad Autónoma de Madrid CVArzobispo Morcillo S/N, E-28029 Madrid (Spain)
© 1992 Karger AG. Bascl 0001-5180/92/1433-0246 $ 2.75A)
Downloaded by: MacQuarie University 137.111.162.20 - 1/21/2020 6:30:55 PM
J.M. Giménez-Amaya
Material and Methods Several rats (Sprague-Dawlcy) were available for this study. A complete description of the anesthetic protocols, perfusion solutions and histochemical processing is available in a previous report [30]. At least, two series in each case were processed adjacently (or close enough to each other) both for CO and for AChE. To reveal the CO activity, we strictly followed the protocol described at great length by Wong-Riley [40]. AChE staining was carried out by a method slightly modified from that of Geneser-Jcnscn and Blackstad [41, 42].
Results The more striking findings of this study are of two sorts. First, we detected a regional as well as a more local compartmentalization in the distribution of CO within the GP. Second, the pallidal localization of CO was not in register with the pallidal distribution of AChE. Figures 1-3 were prepared to illustrate, in a rostrocaudal sequence, the palli dal distribution of CO and, additionally, to compare it with the anatomical localization of AChE within the medial and ventral part of the corpus striatum. Thus, six sections stained for CO were processed together with another set of sections stained for AChE 80 pm apart each from its com panion. In general, the most abundant concentration of pallidal CO was in the most dorsal and lateral parts of the GP close to the internal capsule and to the striatum itself (fig. 1-3). By contrast, ventral pallidal territories, still in the so-called dorsal pallidum [20,43] and the ventral pallidum of Heimer
and Wilson [44], were more weakly stained for CO (fig. 1-3). AChE, however, was found to be higher in those territories just mentioned, and many cells very prominently stained for AChE were detected precisely in those ventral areas of the GP in its middle and caudal thirds (fig. 2b', 3). In addition, the CO was distributed heterogeneously all through the rostrocaudal extension of the GP but in its very rostral pole, whereas the pallidal distribution of AChE was more homogeneous and mainly confined to its caudal half. Moreover, for the CO histochemistry the neuropil was more abundant than the cells, although the variations between neuropil and cells all through the rostrocaudal extension of the GP were not explored in this neuroanatomical study. The very rostral pole of the GP was weakly stained for CO, and, further, it was not feasible to detect any sign of clear heterogeneity in the distribution of this enzyme (fig. la). AChE was also very weak at those pallidal levels (fig. la). More caudal territories in this rostral third of the GP (fig. lb) as well as in its middle and caudal thirds (fig. 2, 3) presented a clear regional design in the histo chemical localization of CO, and such a distribution was very much the opposite of that found for the pallidal locali zation of AChE (fig. lb. b'; fig.2, 3). Thus, dorsal territo ries of the pallidum in its rostral third and dorsal and lateral portions of its middle and caudal thirds presented the high est concentration of pallidal CO. More ventral territories in its rostral third and more ventral and medial parts of its middle and caudal thirds presented a weaker staining for CO. In sharp contrast, however, these pallidal areas just mentioned were highly stained for AChE. This fact was remarkably observed in the rostral part of the middle third of the GP (fig.2a, a') for the dorsoventral histochemical segregation between CO and AChE, and in the caudal part of the middle pallidal third (fig.2b, b') and all through the caudal third (fig.3), for the dorsolateral/ventromedial histochemical segregation of these pallidal markers. The caudal pallidal half in which the most medial territories of the pallidum were more weakly stained for CO was particu larly noticeable for the presence of a great number of large cells highly stained for AChE, very likely corresponding to the large cholinergic cells of the basal nucleus of Meynert (fig.2b'. 3a'. b') [45], Finally, the middle third of the GP was the place in which it was more feasible to detect a more local heteroge neity in the anatomical distribution of CO (see areas of the GP showed by arrows in fig.2a, b). Thus, areas with a higher concentration of CO were sometimes intermingled with areas with a smaller amount of this mitochondrial enzyme.
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To study the histochemical composition of the GP. therefore, may provide us with an interesting neuroanatomical knowledge to better understand the functionality involved in its connectivity within the different basal gan glia circuits. Since a heterogeneous distribution of the mito chondrial enzyme cytochrome oxidase (CO) has been described in the rat's striatum [28-30]. we thought it of interest to explore its distribution in the GP of the same animal and to compare it with the distribution of acetylcho linesterase (AChE), another well-known enzyme of the mammalian basal ganglia. The results described here point to consider the GP of rodents as a heterogeneous structure in which the distribution of CO may follow a regional and a more local compartmental design. It might also account for functional differences regarding its direct hodological rela tionship with other nuclei within the basal ganglia as well as with the thalamus either directly or through the reticular thalamic nucleus [22. 31-39],
a
Fig. 1. Coronal sections through the ros tral GP of the rat’s brain, a. b Distribution of pallidal CO. and those sections are accompa nied respectively by a pair of sections pro cessed for AChE 80 pm apart (a', b'). The rostral pole was stained weakly for CO as well as for AChE (a. a ). A more compartmental distribution of these histochcmical pallidal markers was present in more posterior levels of the rostral pallidal third (arrows in b and b'). Asterisks point to corresponding blood vessels. AC = Anterior commissure; BST = bed nucleus of the stria terminalis; CP = caudate-putamcn complex; FS = fundus striati; IC = internal capsule; SI = substantia innominata of Reichter: VP = ventral palli dum. Scale bar (also for fig.2. 3)=0.3 mm.
Stated briefly, this histochcmical report is in good agree ment with the notion of the rat’s GP to be a heterogeneous structure within the basal ganglia. These results, together with those neuroanatomical studies that show its hodological relationship with a wide variety of prosencephalic and
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mesencephalic structures (see Introduction for references), point to consider the GP as another crucial structure in the processing of information within the basal ganglia of rodents [22. 25-27). In order to offer an adequate interpretation of the results showed in this study, however, a note on method ology should be made. Thus, as pointed out in a previous
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Discussion
a
a
Fig. 2. Coronal sections through the middle GP in the rostrocaudal coordinates of the rat's brain, a. b Localization of pallidal CO. a', b' Pallidal distribution of AChE in close sections to a and b, respectively. Note the dorsoventral (a. a') and the dorsolateral/ ventromedial (b. b') histochemical segrega tion of these pallidal markers. Arrows point to areas with a more local compartmentalization in the GP. in which areas with lower staining for CO were intermingled with oth ers more highly stained. Asterisks point to corresponding blood vessels. CP = Caudateputamen complex: IC = internal capsule; SI = substantia innominata of Reichter; VP = ventral pallidum.
the histochemical parcelation of the GP is very sensitive and, perhaps, highly specific in its functional regulation and expression [30], The same can be said for the tissular distri bution of the enzyme AChE within the GP of rodents. The results offered here show that the GP in the rat is another heterogeneous histochemical structure of the basal ganglia. And since the GP is also very heterogeneous from
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paper [30], it seems conceivable that different histochem ical procedures can induce different pallidal distributions of CO. as it is the case for the striatum [28-30], It might actu ally reflect the fact that the activation of this transmem brane protein of the inner mitochondrial membrane [29] could be made differently according to the experimental methodology used. And further, it would also suggest that
Fig. 3. Coronal sections through the cau dal GP of the rat's brain, a. b Localization of CO. a', b' Distribution of AChE. A clear dorsolateral/vcntromedial compartmental design was visible in this caudal third of the GP. Asterisks point to corresponding blood vessels. B = Nucleus basalis of Meynert; CP=caudate-putamen complex; IC = inter nal capsule; Sl=substantia innominata of Rcichter; Th = thalamus.
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GP (fig. 1-3). and the striatum sends its pallidal connec tions, at least for the rostral striatal territories, in a topo graphical fashion [2,3, 5]. As mentioned before (see Intro duction). the GP. in turn, connects mainly with the subtha lamic nucleus, and also with the substantia nigra, entopeduncular nucleus, striatum, cortex and thalamus, particu larly with the reticular thalamic nucleus. The GP, there
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the hodological point of view [3. 5. 25. 27. 36. 37, 39, 46-48], a new anatomical vision upon its functionality is beginning to emerge [see, for instance, fig.3 in ref.25 and fig. 3 in ref.22], The GP receives its main afferentation from the stria tum, the largest part of the corpus striatum [see ref.5 and references therein]. This structure is in close vicinity to the
fore, receives an important neural information from the striatum that is the first step in the cortical realm of the basal ganglia. The GP. in turn, might transfer that informa tion into different hodological loops within the basal gan glia nuclei (item: GP—» subthalamic nucleus—» entopeduncular nucleus —» GP; item: GP —» substantia nigra pars compacta —» striatum —» GP; item: GP —» striatum —» GP; item: GP —» cortex —» striatum —» GP). Furthermore, the GP might also convey this incoming striatal information outside the basal ganglia, by means of its thalamic relation ship. All this ncuroanatomical data place the GP in the mid dle of very complex circuitous routes in the forebrain of mammals [25-27, 33, 36, 43]. Not only does it appear to start a thalamic realm indirectly through the subthalamic and the endopeduncular nuclei [34], and directly through its thalamic connectivity, particularly with the reticular tha lamic nucleus, but also it may induce feedback regulatory loops regarding its afferentation (e.g. the nigrostriatal dopaminergic projection) [9] and that of the basal ganglia themselves as a whole (e.g. pallidal innervation of the cer ebral cortex) [15]. The fact that it also presents a highly spe cific and heterogeneous distribution of tissular enzymes (e.g. CO and AChE) emphasizes the hypothesis of its role as a crucial step for highly organized neural tasks within the basal ganglia of mammals [25-27].
Obviously, the next step to be taken experimentally in order to better understand the form and function of the GP is to correlate accurately in the same animal the afferent and efferent projections to this structure with the precise distribution of pallidal CO and AChE. This study is pres ently under way, and preliminary results show that, at least for the rostral striatopallidal pathway, dorsal territories in the striatum which present a high concentration of CO innervate the CO recipient of the globus pallidus in the rat [5, 30]. More detailed studies are necessary, however, to correlate hodologically these striatal and pallidal distribu tions of CO, since it is not yet clear whether the gradual decrease in CO within the pallidum corresponds to a regional variation in the distribution of CO within the stria tum and whether the striosomal distribution of CO in the striatum has a correspondence with the more local hetero geneity detected in the GP of the rat [29, 30, 42. 49],
Acknowledgements The author expresses his sincere appreciation to Prof. J.L. Velayos and E. Mengual for their most valuable comments and criticisms, and to J. Hernandez-Claumarchirant, P. Romero and R. Sdnchez-Lozano for their technical assistance in the histochcmical preparations. This study was supported by CICYT grant PB88-0170.
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