50 Bean, A. J., During, M. J., Deutch, A. and Roth, R. H. (1989) J. Neurosci. 9, 4430-4438 51 Vernier, P. etal. (1988)J. Neurochem. 51, 1375-1380 52 Graybiel, A. M. and Chesselet, M-F. (1984) Proc. NatlAcad. ScL USA 81, 7980-7984 53 van der Kooy, D. and Fishell, G. (1987) Brain Res. 401, 155-161 54 Newman-Gage, H. and Graybiel, A. M. (1988) J. Neurosci. 8, 3360-3375 55 Fishell, G. and van der Kooy, D. (1987) J. Neurosci. 7, 1969-1978 56 Steindler, D. A., O'Brien, T. F. and Cooper, N. G. F. (1988) J. Comp. Neurol. 267, 357-369 57 Foster, S. L. etal. (1987)J. Neurosci. 7, 1994-2018 58 Graybiel, A. M. (1984)in Functions of the Basal Ganglia (Ciba Foundation Symposium 107) (Evered, D. and O'Connor, M.,

eds), pp. 114-143, Pitman Press 59 Lundberg, J. M. et aL (1982)in Systemic Role of Regulatory Peptides (Bloom, S. R. etaL, eds), pp. 145-168, Schattauer 60 Schultz, W. et aL (1989) in Neural Mechanisms in Disorders of Movement (Current Problems in Neurology 9) (Crossman, A. R. and Sambrook, M. A., eds), pp. 145-156, Libbey 61 Halpain, 5., Girault, J-A. and Greengard, P. (1990) Nature 343,369-372 62 Herkenham, M. et al. Proc. Natl Acad. Sci. USA (in press) 63 Fatlon, J. H. etal. (1984)Science 224, 1107-1109 64 Goto, S., Hirano, A. and Rojas-Corona, R. R. (1989) Acta Neuropathol. 78, 65-71 65 Reiner, A. (1987) Brain Res. 422, 186-191 66 Chesselet, M-F. and Hook, V. Y. H, (1988) Regulatory Peptides 20, 151-159

Extrinsic connedions of the basal ganglia Andr6 Parent

Andr~ Parentis at the Departmentof Anatomy, Facultyof Medicine, Laval University, Quebec City, Canada 61K7P4.

Recent neuroanatomical studies undertaken with various powerful neural tracing methods have radically changed our concept of the organization of the basal ganglia. This paper briefly reviews some of the findings that have led to the conclusion that the major components of the basal ganglia can no longer be considered as single undifferentiated entities. Instead, each of these structures is characterized by several distinct afferent and efferent chemospecific subsystems by which they can modulate and convey the multifarious information that flows through the basal ganglia. This paper focuses mainly on data obtained in primates, but also stresses the importance of comparison with non-primate species. The circuitry of the basal ganglia is classically known as being composed of multiple intrinsic loops, through which most of the key structures of the system are reciprocally linked, and of a smaller number of projection pathways, which allow the basal ganglia to exert their influence upon distant target structures. Although this general concept of the basal ganglia circuitry is still valid, the numerous neuroanatomical studies undertaken during the past decade, with ever more powerful and sophisticated methods, have greatly expanded our knowledge of the anatomical and functional organization of the basal ganglia. This paper summarizes some of these findings, particularly those that have challenged and even radically changed our way of ttfinking about the arrangement of this set of structures, which plays a crucial role in the control of psychomotor behavior. The striatum: three levels of organization and

heterogeneity The striatum is the largest and major receptive component of the basal ganglia. It receives massive projections from the cerebral cortex, the thalamus and the substantia nigra pars compacta (SNc), and less prominent ones from the pallidum or globus pallidus (GP), the subthalamic nucleus (STN), the dorsal raphe nucleus, and the pedunculopontine tegmental nucleus (PPN). In contrast, the striatum projects massively only to GP and SN. The striatum is composed of a large number of medium spiny 254

projection neurons and a small number of large and medium-sized interneurons 1,2. Among the various striatal afferents, those from the cortex are by far the most prominent. They are of the utmost importance as they impose upon the striatum a pattern of functional regionalization that is maintained throughout the basal ganglia. Most cortical areas project topographically to the striatum. In monkeys the sensorimotor cortex projects mostly to the putamen where a somatotopic representation of the leg, ann and face occurs in the form of obliquely arranged strips 3. In contrast, associative areas of the prefrontal, temporal, parietal and cingulate cortices project mainly to the caudate nucleus4. Finally, afferents from limbic and paralimbic cortical areas as well as from the amygdala and the hippocampus terminate largely in the ventral portion of the striatum, which includes the nucleus accumbens, the deep layers of the olfactory tubercle, and the ventral part of both the caudate nucleus and the putamen5. On the basis of these projections, the striatum can be subdivided into sensorimotor, associative and limbic territories (Fig. 1). However, since overlap exists among the different corticostfiatal projections, these three territories should be viewed more as a continuum rather than stfiatal subdivisions with strict boundaries. Another level of organization is imposed upon the striatum as a result of the fact that cortical areas reciprocally interconnected via corticocortical connections tend to share common zones of termination in Abbreviations Used in the Text CM-PF, centromedian-parafascicular complex GP, globus pallidus or pallidum GPe, external segment of GP GPi, internal segment of GP GPv, ventral palliclum PPN, pedunculopontine nucleus SN, substantia nigra SNc, pars compacta of SN SNr, pars reticulata of SN STN, subthalamic nucleus

© 1990.ElsevierSciencePublishersLtd,(UK) 0166-2236/90/$02.00

TINS, VOI. 13, NO. 7, 1990

striatum 6. This finding suggests that, in addition to delineating large topographic sectors in the striatum, the corticostriatal system is organized according to general functional affiliation of cortical areas. However, it appears that many reciprocally connected areas of the association cortex project to spatially distinct, rather than overlapping, areas of the striatum, and that even in areas where overlap occurs, the terminal fields do not really intermix but form complex interdigitation patterns within longitudinal zones that occupy restricted mediolateral domains of the striatum 4. Like all major striatal afferents, the corticostriatal projection terminates in the form of clusters of various sizes, whose distribution closely follows that of the patches (or striosomes) and matrix compartments recognized after studies of the localization of neurotransmitter-related substances in the striatum 7. In the rat, a recent study revealed that, in contrast to what was previously reported, the compartmental organization of the corticostriatal inputs is related to their laminar origin and only secondarily to cytoarchitectonic areas of origins. In fact, each cortical area C D appears to innervate both patches and matrix, but corticostriatal neurons in infragranular layers project principally to patches, whereas those in supragranular layers send their axons to the matrix. A similar, although more complex, laminar distribution of corticostriatal neurons was reported in primatesg: here, allocortical areas have a higher concentration of corti- dorsal raphe nucleus and PPN. The projections from costriatal neurons in infragranular layers, whereas the different striatal territories remain rather well neocortical areas have a larger number of supragranu- segregated within the pallidal complex. Inputs from lar corticostriatal neurons. The corticostriatal fibers the ventral (lJmbic) striatum terminate preferentially terminate principally on dendritic spines of medium in GPv, the rostral pole of GPe and medial tip of GPi5, spiny projection neurons where they appear to exert whereas those from the associative and sensorimotor an excitatory influence mediated through glutamate 1°. territories occupy the dorsal third and ventral twoThe functional significance of the three levels of thirds of GPe/GPi, respectively 14 (Fig. 1). organization (territorial, associational and compartRetrograde double-labeling studies have revealed mental) disclosed at striatal level, and the way these that, in contrast to a long-standing general belief, the organizational features are maintained or altered striatal innervation of GPe, GPi and SN is not made throughout the basal ganglia circuitry is not yet clear. up of collaterals of a unique striatofugal projection Recent work on patch and matrix compartments system, but originates from separate cell populations suggests that the trans-striatal processing of infor- in the striatum la47. Similar findings have been mation may permit modality-specific and neuro- obtained in the cat TM, but in the rat as much as 40% of chemically specialized channels to be established in striatal projection neurons were reported to send the basal gangliau. However, a proper understanding axon collaterals to both GP and SN 19. Furthermore, of the neural integration that occurs in the basal data obtained in cats and monkeys reveal that the ganglia will not be reached before the correlation between the organization of the corticostriatal and striatopallidal/striatonigral systems is determined.

AS

The globus pallidus: i n f o r m a t i o n f u n n e l o r m u l t i - c h a n n e l device? The GP represents the efferent side of the basal ganglia. It is composed of an internal segment (GPi) and an external segment (GPe), both populated by a relatively small number of large neurons with long dendrites whose arborization is characteristically discoidal12. These dendritic disks lie parallel to the lateral borders of both GPe and GPi, with their largest surface perpendicular to the incoming striatal axons. The GP also comprises a ventral subcommissural portion termed the ventral pallidum (GPv)13; virtually all pallidai neurons use ~,-aminobutyric acid (GABA) as a neurotransmitter. The GP receives major inputs from the striatum and the STN, and less prominent afferents from brainstem structures, such as SNc, ~NS, Vol. 13, No. ~ 1990

~ SM

ABpA~S ~

PU

~ LI

Fig. 1. Schematic representation of the localization of associative (AS), limbic (LI) and sensorimotor (5M) striatal territories in a primate. The drawings are set out in a rostrocaudal order and doublehatched areas indicate zones of overlap. Abbreviations: A C, anterior commissure; CD, caudatenucleus; GPe,external pallidum; GPi, intemal pallidum; GPv, ventral pallidum; IC, internal capsule; LH, lateral hypothalamus; NA, nucleus accumbens; OF, olfactory tubercle; PU, putamen.

Fig. 2. Drawing to illustrate theorigin, neurotransmitter content, and pattern of arborization of the striatopallidal and subthalamopallidal inputs in a primate. The ventralpallidum occurs more rostrally and is not illustrated here. Abbreviations: ENK, enkepha/in;

GABA,

GPe

7-aminobutyric acid; GLU, glutamate; GPe, externalpallidum; GPi, internal pallidum; SP, substance P; PU, putamen; 5TN, subtha/amic nucleus. 255

Fig. 3. A modelofthe organization of the primate globus pallidus based on retrograde doublelabeling studies of its afferent projedions. Abbreviations: CM, centromedian nucleus; FX, fomix; GPe, external pallidum; GPi, intemal pallidum; HB, habenula; LH, lateral hypothalamus,"NB, nucleus basal& PPN, pedunculopontine nucleus,"5N, substantia nigra; 5TN, subthalamic nucleus; ~ t o V A / V L a n d 5TR, striatum; VA, ventral anterior [ ] to V A / V L a n d thalamic nucleus," VL, ventral lateral ~ to CORTEX thalamic nucleus. (Modified from Ref. 2.)

Fig. 4. A modelofthe organization of the primate substantia nigra based on retrograde double/abeling studies of its efferent projections. Abbreviabons: N III, oculomotor nerve root fibers,"PPN, pedunculopontine nucleus; SC superior colliculus; 5Nc, substantia nigra pars compacta; 5Nr, substantia nigra pars reticulata; 5TR-AS, striatal associative territory; 5TR-SM, striatal sensorimotor territory; VA, ventral anterior thalamic nucleus; VL, ventral lateral thalamic nucleus. (Modified from Ref.2.) 256

neurons with large discoidal dendritic domains are particularly numerous. In any event, it would be ¢;':'F:.: . . . . . . ".','.~ important to determine the specific arrangement of the bands formed by the different pallidal afferents. For instance, it would be interesting to know if the striatopallidal and subthalamopallidal bands alternate or are in register with one another (Fig. 2). The organization of efferent projections of GP has been reviewed extensively elsewhere 2 and is summarized schematically in Fig. 3. The GPe has more limited efferent projections than GPi; its most prominent projection is to STH, but it also gives rise to sparser efferents terminating in the striatum and SN. In contrast, GPi projects massively to the ventral tier thalamic nuclei, the centromedian, the lateral habenula and PPN. A recent anterograde labeling study of GPe and GPi connections with the lectin Phaseolus vulgaris-leucoagglutinin has revealed that GPi efferent fibers display a pattern that is strikingly different CM [ ] to HB in each of these target structures and that both pallidal segments are probably reciprocally linked 26. This PPN [ ] t o S N a n d STR hitherto unknown GPe-GPi interconnection could I-~ tOSTN play a crucial role in the functional organization of the basal ganglia. Retrograde double-labeling studies have shown that in regard to its efferents the GPi in striatal innervation of GPe and GPi originates from primates is organized in a pattern that is markedly distinct clusters of neurons that lie within the striatal different from that of its homologue in the rat, the matrix 2°,2~. Striatal neurons projecting to GPe and entopeduncular nucleus 27. This pattern consists of GPi use GABA as their main neurotransmitter. 'associative/sensorimotor', 'limbic' and 'reticular' However, striatal neurons that terminate in GPe also (cholinergic) concentric zones, with most neurons in contain enkephalin, whereas those terminating in GPi the large central associafive/sensorimotor zone branchare enriched with substance P (Fig. 2). Another ing profusely to the thalamus and the brainstem important recent finding is that the striatopallidal tegmentum. These pallidal neurons may be the source fibers terminate in the form of bands lying parallel to of much redundancy or parallel processing in the basal the medullary laminae 2,~4 (Fig. 2). A similar band-like ganglia circuitry, but unfortunately, the descending pattern has been observed at pallidal level after pallidal projection is still largely ignored in the current injections of anterograde tracers in STN 22,23, and thus schemes of the functional organization of the basal appears to be the most characteristic feature of the ganglia. The GPv projects to STN and SN, but also to pattern of innervation of GP in primates. It is likely limbic-related structures, such as the mediodorsal that the band-like terminal patterns displayed by thalamic nucleus, the lateral habenula, the hypothalamost pallidal afferents, including those from the mus and the amygdala 28. Thus, GPv can convey brainstem 24,25, correspond to zones where pallidal information from the limbic striatal territory not only into the basal ganglia circuitry, but also back into the limbic system circuitry. SNc Taken together, these findings indicate that the two pallidal segments as well as the ventral pallidum ~ , ~ o ~ z~ ~ to STR~AS in primates are differentially modulated by various chemospecific neuronal subsystems. The differential modulation of the two pallidal segments could play a ,,o.,:.. °0Oo°0O::,o crucial role in the development of hyper- and hypo.'.• .:~ • ~..~o o ° t l e l eoe °o % e;~ •."> ~ ~ oo l = = * o l * e •::.'. ~ ° io e== e o =Q = e oo~ kinetic disorders 29. On the other hand, although some ...:' ..~ ¢'..':.:: : o O o • ~, v.......~ "**" , * * * . O°Oo " . o % anatomical studies have emphasized the large degree v.v.v. , , ~ ~..;, e.... oOogOO oO .~ ' *" "" • oOO°°°o ..,, N of convergence that occurs along the striatopallido• ...:.~ ~.', .*---.2~oo#O .o% nigral system 12, the data reviewed above suggest that ..~ . p.* °. ,oO o • . . . . * * ° * \ ~!., ~ ,.....; .oO........ \ •.:.' e." • .\ , ,o::'..o the integration of information at pallidal level is largely \ ........ done via multiple, parallel subcircuits or channels, \ ~,~,-.,; . . . . . . " ~ . . . o ,Oo o-#~ • ° ° ° ~"~ o o which remain rather well segregated 3°. At thalamic \ ?o SNr ~ - ~ "-'~. . . . :0 levels, projections from the various portions of the pallidal complex also remain separated from one another, and the pallidothalamic projection system as D to VA/VL a whole terminates in a thalamic territory that is ~----~]to PPN distinct from those receiving nigrothalamic and cerebellothalamic inputs 31. In turn, thalamic neurons ~ t o VA/VLand PPN receiving inputs from the basal ganglia project to distinct frontal premotor cortical areas, whereas ~ t o SC those innervated by the cerebellum project directly to - - ] t o SC and VA/VL the motor cortex 3°. TINS, Vol. 13, No. 7, 1990

The substantia nigra: multicollateral versus nigrosomal organization In contrast to GP, SN in primates receives a more massive input from the associative striatal territory than from the sensorimotor territory, the former terminating roughly in the rostromedial two-thirds of SN and the latter in its caudolateral third 14. The pattern of distribution of the two inputs was found to be strikingly complementary, so that SN areas containing terminals from the sensorimotor territory were largely devoid of terminals from the associative territory, and vice versa. The projection neurons in the limbic territory terminate mostly medially, but fibers also extend laterally and caudally in SN 5. In the rat striatal projection neurons lying in patches were reported to project to SNc, whereas those in the matrix project to SNr 32. The pattern is more complex in cats where patches preferentially project to the densocellular zone of SNc, whereas the matrix innervates mainly the lateral portion of SN TM. In monkeys, the patch and matrix representation at SN level remains to be investigated. In contrast to SNr, whose GABAergic neurons branch extensively to the thalamus, superior colliculus and PPN, the SNc in primates is composed of closely interlocked clusters of dopaminergic neurons projecting either to the associative (head of caudate) or sensorimotor (caudal two-thirds of putamen) striatal territories 33 (Fig. 4). Interestingly, compartments that are either rich or poor in acetylcholinesterase staining occur in SNc of primates and this compartmentalization appears to correspond, at least in part, to the clustering of SNc neurons observed after caudate/putamen injections34. This striking 'nigrosoreal' arrangement of SNc dopaminergic neurons could reflect several constraints including both territorial and compartmental aspects of the striatal organization. The subthalamic n u c l e u s - a nodal point in basal ganglia circuitry The STN is particularly well developed in primates. It is composed of a multitude of medium-sized and densely packed projection neurons and a few small interneurons. Like the striatum, it receives a massive and topographically organized projection from the cerebral cortex 1,~. It also receives a prominent input from GPe and, in turn, projects to both GP segments 35. The nucleus is also reciprocally connected with the PPN and sends less prominent efferents to the striatum and SN 2. Recent anterograde and retrograde labeling studies have revealed that STN, like most other basal ganglia components in primates, comprises several separate projection systems arising from distinct sensorimotor, associative and limbic territories 23,36 (Fig. 5). Hence, the organization of STN in primates is markedly different from the same structure in rodents, whose neurons project to both GP and SN largely via axon collaterals 37. Furthermore, recent investigations have shown that STN projections to GPe and GPi also arise largely from separate neuronal populations in primates: neurons that project to GPe are more numerous and more laterally located in STN than those projecting to GPP 7. The significance of the differences noted between rodents and primates in regard to the organization of

TINS, Vol. 13, No. 7, 1990

LI

D

I U/GP

Fig. 5. Diagram summarizing the output organization of the primate subthalamic nucleus as revealed after retrograde and anterograde labeling studies in the squirrel monkey (Saimiri sciureus). Abbreviations: CD, caudate nucleus; D, dorsal; GP, globus pallidus or pallidum; GPe, external pallidum; GPv, ventral pallidum; L, lateral; PU, putamen; SN, substantia nigra.

STN remains to be elucidated, but it may have some relation to the fact that, in contrast to the dramatic changes observed in primates, no significant alteration in motor behavior can be seen after lesion of STN in non-primates. The STN has long been thought to act as a strong inhibitor of the two major output structures of the basal ganglia (GPi and SNr), using GABA as a neurotransmitter. In contrast, recent

I STR ~ SM

II

STR

AS

CTX ~ SM

'PVG

I FB ~ LI

Fig. 6. Diagram summarizing the output organization of the primate centromedian (CM)-parafascicular (PF) complex as revealed after retrograde and anterograde labeling studies in the squirrel monkey (Saimiri sciureus). Abbreviations: CTX-SAA, cortical sensorimotor areas; FB-LI, forebrain limbic structures, including striatal limbic territory, hypothalamus and amygdala; H, habenulo-interpeduncular tract; PVG, periventricular gray; SPF, subparafascicular nucleus; STR-AS, striatal associative territory; STR-SM, striatal sensorimotor territory. 257

studies revealed that STN exerts a powerful, glutamatergic, excitatory influence upon its target structures so that it is now considered as one of the driving forces of the basal ganglia 29,37.

The centromedian-parafascicular complex as part of the basal ganglia The thalamus projects massively to the striatum and much less so to GP and STN 1,2. Although the anterior intralaminar nuclei and the centromedianparafascicular complex (CM-PF) are the major sources of this projection, other thalamic nuclei, including those of the ventral tier, the midline and the posterior group, also contribute 3s. In primates, CMPF is greatly enlarged and provides a massive and orderly projection to the striatum. CM selectively receives GPi inputs and, in turn, projects massively to the sensorimotor territory of the striatum where it terminates in the form of obliquely oriented, parallel bands 39. This arrangement strikingly resembles the pattern of terminal labeling of the sensorimotor cortical input to the putamen 3, but the correspondence between these two band-like terminal patterns remains to be established. In contrast to CM, PF receives inputs from a wide variety of sources, including limbic-related structures 38 and, in turn, projects to the associative and limbic territories of the striatum where it terminates in a patchy manner 39. Inputs to the associative and limbic striatal territories appear to arise from the dorsal and the ventral portion of PF, respectively (Fig. 6). A significant projection to the limbic territory also arises from the subparafascicular nucleus whose boundaries with PF are fuzzy. In regard to the compartmental organization of the striatum, both CM and PF appear to project to the matrix compartment 39. CM-PF is also reciprocally linked with the cerebral cortex, and its projection to the cortical sensorimotor areas, at least in the squirrel monkey (Saimiri sciureus), appears to arise mainly from a crescentshaped zone, which forms the ventrolateral border of CM-PF (Fig. 6). Taken together, these findings support the concept that CM-PF is a crucial component of the basal ganglia circuitry39,40. They further suggest that the two major components of this complex are involved in complementary aspects of basal ganglia function, CM being a nodal point in the sensorimotor circuitry and PF (and the subparafascicular nucleus) an important relay in the associativelimbic circuitry of the basal ganglia. Concluding remarks In the light of the above-mentioned findings, the primate basal ganglia can be viewed as a set of highly heterogeneous structures composed of separate neuronal populations giving rise to distinct chemospecific projection subsystems. This unique arrangement allows these structures to integrate, modulate and convey the information that flows through the basal ganglia in a very specific and orderly fashion before it is sent back to the cerebral cortex and brainstem. In rodents, neuronal populations in basal ganglia are more homogeneous and appear to exert their influence mostly through highly collateralized projection systems. We believe that the understanding of such 258

important species differences represents one of the major challenges to future research on basal ganglia.

Selected references 1 Carpenter, M. B. (1981)in Handbook of Physiology (Sect. 1: The Nervous System II) (Brooks, V. B., ed.), pp. 947-995, American Physiological Society 2 Parent, A. (1986) Comparative Neurobiology of the Basal Ganglia 3 K0nzle, H. (1975) Brain Res. 88, 195-209 4 Selemon, L. D. and Goldman-Rakic, P. (1985) J. Neurosci. 5, 776-794 5 Haber, S. N., Lynd, E., Klein, C. and Groenewegen, H. J. (1990) J. Comp. Neurol. 293,282-298 6 Van Hoesen, G. W., Yeterian, E. H. and Lavizzo-Mourey, R. (1981) J. Comp. Neurol. 199, 205-219 7 Graybiel, A. M. and Ragsdale, C. W., Jr (1983) in Chemical Neuroanatomy(Emson, P. C., ed.), pp. 427-504, Raven Press 8 Gerfen, C. R. (1989) Science 246, 385-388 9 Arikuni, T. and Kubota, K. (1986) J. Comp. Neurol. 244, 492-510 10 Somogyi, P., Bolam, J. P. and Smith, A. D. (1981) J. Comp. Neurol. 195, 567-584 11 Malach, R. and Graybiel, A. M. (1986) J. Neurosci. 6, 3436-3458 12 Percheron, G., Yelnik, J. and Francois, C. (1984) J. Comp. Neurol. 227, 214-227 13 Heimer, L., Switzer, R. D. and Van Hoesen, G. W. (1982) Trends Neurosci. 5, 83-87 14 Smith, Y. and Parent, A. (1986) Neuroscience 18, 347-371 15 Parent, A., Bouchard, C. and Smith, Y. (1984) Brain Res. 303, 385-390 16 F4ger, J. and Crossman, A. R. (1984) Neurosci. Left. 49, 7-12 17 Parent, A., Smith, Y., Filion, M. and Dumas, J. (1989) Neurosci. Left. 96, 140-144 18 Beckstead, R. M. and Cruz, C. J. (1986) Neuroscience 19, 147-158 19 Loopuijt, L. D. and Van der Kooy, D. (1985) Brain Res. 348, 86-89 20 Jim4nez-Castellanos, J. and Graybiet, A. M. (1989) Neuroscience 32,297-321 21 Gim4nez-Amaya, J. M. and Graybiel, A. M. (1990) Neuroscience 34, 11-126 22 Nauta, H. J. W. and Cole, M. (1978) J. Comp. Neurol. 180, 1-16 23 Smith, Y., Hazrati, L-N. and Parent, A. (1990) J. Comp. Neurol. 294, 306-323 24 Lavoie, B., Smith, Y. and Parent, A. (1989) J. Comp. NeuroL 289, 36-52 25 Lavoie, B. and Parent, A. J. Comp. NeuroL (in press) 26 Parent, A., Hazrati, L-N. and Lavoie, B. in The Basal Ganglia Ill (Bernardi, G., Carpenter, M. B. and Di Chiara, G., eds), Plenum Press (in press) 27 Van der Kooy, D. and Carter, D. A. (1981) Brain Res. 211, 15-36 28 Haber, S. N., Groenewegen, H. J., Grove, E. A. and Nauta, W. J. H. (1985) J. Comp. NeuroL 235, 322-335 29 Albin, R. L., Young, A. B. and Penny, J. B. (1989) Trends Neurosci. 12, 366-375 30 Alexander, G. E., DeLong, M. R. and Strick, P. L. (1986) Annu. Rev. Neurosci. 9, 357-381 31 Ilinsky, L. A. and Kultas-Ilinsky, K. (1987) J. Comp. Neurol. 262,331-364 32 Gerfen, C. R. (1984) Nature 311,461-464 33 Parent, A., Mackey, A. and De Bellefeuille, L. (1983) Neuroscience 10, 1137-1150 34 Jim4nez-Castellanos, J. and Graybiel, A. M. (1987) Brain Res. 437, 349-354 35 Carpenter, M. B., Carleton, S. C., Keller, J. T. and Conte, P. (1981) Brain Res. 224, 1-29 36 Parent, A. and Smith, Y. (1987) Brain Res. 436, 296-310 37 Kitai, S. T. and Kita, H. (1987) in The Basal Ganglia II (Carpenter, M. B. and Jayaraman, A., eds), pp. 357-373, Plenum Press 38 Royce, G. J. (1987) in The Basal Ganglia II (Carpenter, M. B. and Jayaraman, A., eds), pp. 293-319, Plenum Press 39 Sadikot, A. F., Parent, A. and Fran(~ois, C. (1990) Brain Res. 510, 161-165 40 Francois, C., Percheron, G., Yelnik, J. and Tandie, D. (1988) Brain Res. 473, 181-186

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