Lili-Naz Hazrati

Functional anatomy of the basal ganglia. I. The cortico-basal ganglia-thalamo-cortical loop

This paper reviews some of the recent findings on different aspects of the anatomical organization of the basal ganglia. Attempts have been made to delineate the anatomical substrate of information processing along the cortico-basal ganglia-thalamo-cortical loop. Emphasis has been placed on data obtained with highly sensitive anterograde tract-tracing methods applied to the study of the main axis of the loop, which is composed of the striatum, the pallidum, and the substantia nigra. These findings have highlighted the complexities of the organization of the intrinsic basal ganglia circuitry, which comprises multiple modular units that are distributed according to highly ordered and repetitive patterns. Such an arrangement is well suited to convey cortical information in a highly specific manner throughout the basal ganglia. The basal ganglia circuitry is also designed so as to modulate in a precise manner the neuronal activity of several brain functional systems, which are involved in the direct control of different aspects of psychomotor behavior. Of utmost importance is the action of the basal ganglia on thalamocortical premotor neurons. It is through these neurons, which can be considered as a sort of final common pathway, that the basal ganglia ultimately influence the complex neuronal computation that goes on at cortical level.

Anatomical aspects of information processing in primate basal ganglia

Recent studies with double-anterograde tract-tracing methods have shed new light on the organization of the basal ganglia circuitry in primates. This paper briefly reviews some of these findings and provides a personal interpretation of their possible functional significance. Emphasis is placed on the fact that the striatum and the subthalamic nucleus have multiple representations in the two major output structures of the basal ganglia, namely the internal segment of the globus pallidus and the substantia nigra pars reticulata. It is hypothesized that this multiple representation serves as a means of amplifying and diversifying the striatal and subthalamic influences upon thalamocortical neurons that is mediated through the globus pallidus and the substantia nigra. Furthermore, evidence for the highly ordered organization of the striatopallidal and subthalamopallidal projections, which converge onto single pallidal neurons according to different but highly specific patterns, is taken as an indication that the subthalamic nucleus uniformly excites a vast collection of pallidal neurons, whereas the striatum exerts a more specific inhibitory control upon selected subsets of subthalamically driven pallidal neurons.

Evidence for interconnections between the two segments of the globus pallidus in primates: a PHA-L anterograde tracing study.

Small injections of the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) in the external segment of the pallidum (GPe) in the squirrel monkey (Saimiri sciureus) and in the rhesus monkey (Macaca mulatta) led to anterograde labeling of fibers in the internal segment of the pallidum (GPi). These fibers formed numerous large varicosities reminiscent of terminal boutons, which closely surrounded GPi cell bodies and primary dendrites. Conversely, PHA-L injections in the GPi of squirrel monkeys produced anterograde fiber labeling in the GPe. However, in contrast to fibers in GPi, those in GPe did not make prominent pericellular contacts. Instead, they displayed a rather linear course, had long intervaricose segments, and appeared to contact several GPe neurons along their course by close appositions on cell bodies and primary dendrites. These results suggest the existence of a reciprocal connection between the two pallidal segments, which may play a crucial role in the functional organization of the basal ganglia in primates.

Projection from the external pallidum to the reticular thalamic nucleus in the squirrel monkey

Small injections of biocytin in the external segment of the pallidum (GPe) of the squirrel monkey (Saimiri sciureus) led to anterograde labeling of fibers in the thalamic reticular nucleus (NRT). These fibers reached NRT by coursing along the ventral tip of the internal capsule or by directly piercing the internal capsule more dorsally. They arborized profusely within the entire rostrocaudal extent of the nucleus. Within NRT, biocytin-labeled fibers were long, slightly varicosed, and emitted numerous short collaterals whose terminal portions consisted of clusters of large varicosities. Some of these varicosities were closely apposed to cell bodies and proximal dendrites of NRT neurons. Small injections of wheat germ-agglutinated horseradish peroxidase in the rostral pole of NRT led to retrograde cell labeling within the entire rostrocaudal extent of GPe. These retrogradely-labeled cells did not display immunoreactivity for choline acetyltransferase. Hence, beside the well-established projection from the internal pallidum to the thalamus, our findings support the existence of another pallidothalamic projection whereby GPe neurons could exert a powerful influence upon the thalamocortical neurons via a relay in NRT.

Contralateral pallidothalamic and pallidotegmental projections in primates : an anterograde and retrograde labeling study

Unilateral injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) in the internal segment of the pallidum (GPi) of the squirrel monkey (Saimiri sciureus) led to anterograde labeling of fibers ipsilaterally in the following thalamic nuclei: ventral anterior (VA), ventral lateral (VL), centromedian (CM), and lateral habenula (Hbl). The labeled fibers reached these ipsilateral thalamic nuclei by coursing along or through the ansa lenticularis, the lenticular and thalamic fasciculi, and the Forels fields. They arborized profusely in VA/VL nuclei where they displayed small glomerule-like formations. Numerous labeled fibers also occurred in the CM. Most of them were long, varicose and gave rise to shorter fibers that formed a dense terminal field covering a large portion of the CM. A small but dense terminal field composed of delicate fibers and extremely fine terminals was noted in the Hbl. A large contingent of labeled fibers were seen to cross the midline, principally at the rostral pole of the CM and in the supramammillary decussation, to reach the contralateral thalamus where they arborized profusely in the VA/VL and CM nuclei, but not in the Hbl. The patterns of termination of these contralateral pallidothalamic fibers were strikingly similar to those observed ipsilaterally. Other anterogradely labeled fibers were also noted bilaterally in the pedunculopontine nucleus (TPP) and ipsilaterally in the external segment of the pallidum (GPe) and in the putamen. Complementary, double-labeling, retrograde studies involving the injection of nuclear yellow in the VA/VL and CM nuclei and Fast blue in the TPP, confirmed the existence of contralateral pallidothalamic and pallidotegmental projections. The number of retrogradely labeled cells in the contralateral GPi amounted approximately to 10-20% that in the ipsilateral GPi. These experiments further indicated that contralaterally projecting pallidothalamic neurons exhibited a high degree of axonal collateralization, the majority of its neurons projecting also to the contralateral TPP. Cells retrogradely labeled with the tracer injected into the thalamus were also encountered bilaterally in the thalamic reticular nucleus. Taken together, the results of these anterograde and retrograde investigations indicate that the contralateral pallidothalamic projection involves a relatively small population of GPi neurons, but that these neurons arborize extensively in their contralateral thalamic targets. Furthermore, the presence of retrogradely labeled cells in the ipsi- and contralateral reticular thalamic nucleus indicates that the VA/VL and CM nuclei, which receive a massive input from the GPi, are under the bilateral influence of this perithalamic nucleus. Such contralateral projections could play a major role in the subcortical organization of the bilateral aspect of normal basal ganglia function.(ABSTRACT TRUNCATED AT 400 WORDS)

Projection from the deep cerebellar nuclei to the pedunculopontine nucleus in the squirrel monkey

Large injections of the anterograde tracer biocytin in the deep nuclei of the cerebellum of squirrel monkeys (Saimiri sciureus) led to a massive labeling of the superior cerebellar peduncle fibers which could be followed up to their major termination site in the thalamus. Along their course through the brainstem, biocytin-labeled fibers emitted fine collaterals that arborized profusely within the entire rostrocaudal extent of the pedunculopontine nucleus (PPN). These fibers were long, slightly varicose, and broke off into numerous shorter and thinner fibers whose terminal portions consisted of a few large varicosities that were often closely apposed to dendrites and cell bodies of PPN neurons. Some PPN cells that were contacted displayed immunoreactivity for choline acetyltransferase. Ultrastructural analysis revealed that synapses formed by cerebellar fibers in PPN were of the asymmetric type and occurred predominantly on dendrites of PPN neurons. Thus, beside the well established cerebellothalamic projection, our findings reveal the existence of a cerebellotegmental projection, whereby the cerebellum may influence the basal ganglia and/or the thalamus via a relay in PPN.

Substantia nigra pars reticulata projects to the reticular thalamic nucleus of the cat: a morphological and electrophysiological study

The projections of substantia nigra pars reticulata (SNr) toward the reticular (RE) thalamic complex of cat were studied morphologically and electrophysiologically. Numerous SNr cells were retrogradely labeled following injections of horseradish peroxidase conjugated to wheat-germ agglutinin (WGA-HRP) in the rostral and rostrolateral part of the RE thalamic nucleus. Iontophoretic injections of Phaseolus vulgaris leucoagglutinin (PHA-L) in the SNr confirmed that this retrograde labeling was not a consequence of tracer diffusion in neighboring structures, but reflected a genuine SNr projection to the RE thalamic nucleus. Indeed, widely branched and varicose PHA-L-positive fibers were found in the rostral and rostrolateral pole of the RE thalamic nucleus following PHA-L injections in the SNr. Furthermore, in agreement with previous data indicating that nigrothalamic cells are GABAergic, electrical stimulation of the SNr evoked a short-latency inhibitory effect acting on both spontaneous and cortically-evoked discharges of most RE thalamic neurons. These results are discussed in light of the possible role of the SNr and RE thalamic complex in attentional processes.

The thalamic reticular nucleus does not send commissural projection to the contralateral parafascicular nucleus in the rat

The reticular nucleus of the thalamus (NRT) projects to virtually all thalamic nuclei ipsilaterally. In addition, recent studies suggest that NRT sends contralateral projections through an intrathalamic commissural fiber system to several thalamic nuclei, including the NRT itself. In the present study we used retrograde cell labeling, multi-unit anterograde labeling and immunohistochemical methods to study both ipsi- and contralateral NRT projection to the parafascicular nucleus (Pf) in the rat. Injections of the fluorescent tracers true blue or fluorogold in Pf led to massive retrograde cell labeling in rostral and dorsal portions of the ipsilateral NRT, whereas the same sectors of the contralateral NRT were devoid of labeling. Some retrogradely labeled cells were nevertheless present on the contralateral side in the borderline region between NRT and the zona incerta (ZI). Retrograde cell labeling experiments with cholera toxin B subunit (CTb) combined to immunohistochemistry for parvalbumin (PV) and calbindin D-28k (CB) indicated that the few retrogradely labeled cells encountered at the border between NRT and ZI displayed immunoreactivity for CB but not for PV. Since PV and CB label neurons belonging to NRT and ZI, respectively, it is concluded that these contralateral retrogradely labeled cells belong to ZI and not to NRT. Multi-unit cell anterograde labeling experiments with biocytin showed that NRT cells that project to Pf arborize extensively only on the ipsilateral side. The same approach, however, has revealed NRT cells projecting to both ipsi- and contralateral ventromedial thalamic nuclei. The axon of these NRT neurons arborizes more profusely ipsilaterally than contralaterally. These results reveal that the NRT projection to Pf in rodents is strictly unilateral. These findings are at variance with the emerging concept that NRT exerts a prominent bilateral influence upon most thalamic nuclei.

Chapter 6 Striatal and subthalamic afferents to the primate pallidum: interactions between two opposite chemospecific neuronal systems

Publisher Summary The pallidum or globus pallidus in primates plays a crucial role in the integration of neural information that flows through the cortico-basal ganglia-cortical loop. This key structure of the basal ganglia is mostly composed of large projection neurons that integrate information arising principally from the striatum and the subthalamic nucleus. These two major sources of pallidal afferents are the only basal ganglia components that receive massive and direct projections from the cerebral cortex. The subthalamic nucleus is known to exert a glutamate-mediated excitation upon pallidal neurons, whereas the striatum inhibits pallidal cells through the use of y-aminobutyric acid (GABA) as a neurotransmitter. Thus, a detailed knowledge of the anatomical framework for interactions between these two opposite chemospecific pallidal afferents is a prerequisite for a proper understanding of the functional organization of the basal ganglia. This chapter describes some of the most recent findings pertaining to the organization of the striatopallidal and subthalamopallidal projections in the squirrel monkey. A special attention is paid to the recent data obtained with the double anterograde labeling method demonstrating that the excitatory glutamatergic subthalamopallidal projection and the inhibitory GABAergic striatopallidal projection converge upon single pallidal neurons in primates.

The Pallidum as a Dual Structure in Primates

This paper reviews some of our most recent findings on the organization of the afferent and efferent connections of the globus pallidus (GP) in the squirrel monkey (Saimiri sciureus). Its main purpose is to demonstrate that even though all pallidal neurons express the same phenotype in terms of both morphology and chemospecificity, the analysis of afferent and efferent connections of GP reveals that this major component of the basal ganglia is in fact a dual entity in primates.