Review
The pallidofugal projection system in primates: evidence for neurons branching ipsilaterally and contralaterally to the thalamus and brainstem

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Abstract

This paper summarizes the results of some of our previous neuroanatomical studies on the pallidofugal projections in squirrel monkeys and also reports more recent data obtained with double retrograde and single axon tracing methods. Injections of anterograde tracers in the internal pallidum label axons that reach the ventral tier, centromedian and lateral habenular thalamic nuclei, as well as the pedunculopontine tegmental nucleus. The pallidofugal projections are composed of axons that branch to the ventral tier and pedunculopontine nuclei, and to ventral tier and centromedian nuclei. Double retrograde labeling with fluorescent tracers and single axon tracing confirm this high degree of collateralization. Furthermore, some pallidal labeled axons cross the midline and arborize contralaterally in the major pallidal targets. Double retrograde fluorescent labeling experiments support these findings. Pallidal axons that branch ipsilaterally as well as contralaterally to the thalamus and brainstem could play a crucial role in the functional organization of primate basal ganglia.

Introduction

The internal segment of the globus pallidus (GPi) in primates, the presumed homologue of the entopeduncular nucleus (EN) in non-primates, is a major output nucleus of the basal ganglia (Carpenter, 1981, Parent and Hazrati, 1995). The GPi in primates is known to project to several thalamic nuclei, principally the ventral anterior (VA)/ventral lateral (VL) nuclei (the so-called ventral tier nuclei), the centromedian (CM)/parafascicular (Pf) complex, the lateral habenular nucleus (HL), and it also sends input to the pedunculopontine tegmental nucleus (PNN) of the midbrain-pontine tegmentum (Nauta and Mehler, 1966, Kuo and Carpenter, 1973, Kim et al., 1976, DeVito and Anderson, 1982, Parent and De Bellefeuille, 1982, Parent and De Bellefeuille, 1983, Parent and Hazrati, 1995). The pioneering axonal degeneration study of Nauta and Mehler (1966) has led to the suggestion that the pallidal projections to the thalamus and brainstem arise mostly from axon collaterals of the same GPi neurons. This view received support from electrophysiological (antidromic invasion) experiments (Filion and Harnois, 1978, Harnois and Filion, 1980, Harnois and Filion, 1982) and double retrograde cell labeling studies (Parent and De Bellefeuille, 1982, Parent and De Bellefeuille, 1983). In view of the role that the GPi plays in the overall organization of the basal ganglia, we thought it useful to briefly review our knowledge of the anatomical organization of the pallidofugal projections in primates.

The present paper stems from a talk that was given at a symposium entitled ‘Thalamic Integration of Basal Ganglia Signals’ as part of the 1998 Forum of European Neuroscience held in Berlin. The aim of the paper is to provide a personal view of the organization of the pallidofugal projection system in primates. The present contribution should by no means be considered a detailed review on the subject, and we apologize to all the investigators whose relevant work has not been cited here because of space limitation. The first part of the paper consists of a brief summary of the results of our previous studies on the pallidofugal projections undertaken with both retrograde and anterograde labeling methods in the squirrel monkeys. This sets the scene for the second part of the paper which deals with more recent data obtained with double retrograde cell labeling procedures and with single axon tracing methods in both squirrel and cynomolgus monkeys. In this paper, emphasis will be placed on the contralateral pallidothalamic projections, which may play a crucial role in the functional organization of the primate basal ganglia.

Section snippets

Fluorescence double retrograde labeling experiments

Twenty male, adult (body weight, 900–1100 g) squirrel monkeys (Saimiri sciureus) were used for fluorescence double retrograde labeling experiments. We employed a procedure based on the retrograde transport of two or more substances that fluoresce maximally at different wavelengths and which is particularly suitable for the study of neuronal systems having multiple axonal processes terminating in different brain areas (Van der Kooy et al., 1978). All animals were anesthetized with ketamine

Thalamus (VA/VL) and habenula (HL) injections

In animals that received injections of one fluorescent tracer into the VA/VL nuclei and the complementary tracer into the HL on the same side of the brain, a large number of neurons retrogradely labeled with the tracer injected into the thalamus occurred in the central two-thirds of the ipsilateral GPi (Fig. 1A). In contrast, pallidal neurons containing the tracer injected into the habenula were much less numerous and mostly confined to the periphery of the GPi. These pallidohabenular neurons

Origin and collateralization of the pallidofugal projections

Our retrograde cell labeling studies have revealed that neurons projecting to the VA/VL nuclei occurred in the core of the GPi along its entire rostrocaudal extent, whereas those projecting to the CM formed two more or less continuous clusters lying in the dorsolateral and ventromedial portions of the GPi. Pallidal neurons projecting to the PPN were also confined to the core of the GPi, whereas those projecting to the habenula were located more peripherally and abounded particularly at the

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