Axonal collateralization in primate basal ganglia and related thalamic nuclei

Abstract

This paper provides an overview of the major organizational features of the basal ganglia and related thalamic centers, as delineated by the application of single-axon or single-cell labeling procedures in primates. These studies have revealed that the striatum, the external pallidum and the subthalamic nucleus harbor several types of projection neurons endowed with a highly collateralized axon that allows these neurons to interact with most components of the basal ganglia. In contrast, the internal pallidum, which is a major output structure of the basal ganglia, contains only two types of projection neurons. First, there is a minority of "limbic" pallidal neurons with a poorly branched axon that arborized profusely within the lateral habenula, which stands out as the most densely innervated pallidal target. Second, there is a majority of pallidal "motor" neurons with a long (total axonal length up to 27 cm) and highly branched axon that provides collaterals to the ventral tiers thalamic nuclei, the brainstem pedunculopontine nucleus and the centre médian/parafascicular thalamic complex. This type of axon allows internal pallidal neurons to send efferent copies of the same information to the thalamus and brainstem and hence influence various neuronal systems scattered throughout the neuraxis. Pallidal information is conveyed to the cerebral cortex and the striatum via the thalamus, while it is projected back to different components of the basal ganglia via the numerous reentrant pathways that arise from the pedunculopontine nucleus. Virtually all neurons in the centre médian thalamic nucleus innervate massively the striatum and less prominently the primary motor cortex, which in turn projects to the striatum directly or via a collateral from long-range corticofugal pyramidal axons. The results call for a reappraisal of our current concept of the anatomical and functional organization of basal ganglia, which play a crucial role in sensorimotor integration. Our data indicate that basal ganglia and related thalamic nuclei form a widely distributed neuronal network, whose elements are endowed with a highly patterned set of axon collaterals. This morphological feature allows a complex and exquisitely precise interaction between the various basal ganglia and related thalamic nuclei. The elucidation of this finely tuned network is needed to understand the complex spatiotemporal sequence of neural events that ensures the flow of cortical information through the basal ganglia and thalamus.

Mechanisms and Targets of Deep Brain Stimulation in Movement Disorders

“…CM ϭ centromedian nucleus of thalamus; CMA ϭ cingulate motor area; DCN ϭ deep cerebellar nuclei; GPe ϭ globus pallidus pars externa; GPi ϭ globus pallidus pars interna; M1 ϭ primary motor cortex; Pf ϭ parafascicular nucleus of thalamus; PMC ϭ premotor cortex; PN ϭ pontine nuclei; PPNc ϭ pedunculopontine nucleus pars compacta; PPNd ϭ pedunculopontine nucleus pars dissipatus; RTh ϭ reticular nucleus of thalamus; SMA ϭ supplementary motor cortex; SNc ϭ substantia nigra pars compacta; SNr ϭ substantia nigra pars reticulata; STN ϭ subthalamic nucleus; VA ϭ ventroanterior thalamus; Vim ϭ ventral intermediate nucleus of thalamus; VL ϭ ventrolateral thalamus. Figure compiled from data in Pahapill and Lozano, 81 Parent and Parent 168 , and Alexander et al 169 several minutes before, during, and after HFS with parameters (100 A amplitude, 130 Hz frequency, and 60 s pulse width) that improved contralateral rigidity in parkinsonian monkeys. In that study, therapeutic stimulation decreased the mean firing rate in the majority of STN neurons, from 19 Hz to 8 Hz.…”

Single-axon tracing and three-dimensional reconstruction of centre médian-parafascicular thalamic neurons in primates

“…This thalamic complex is composed of at least three types of neurons with different axonal branching patterns that allow this brain center to influence its different target sites in a highly specific manner. Our previous single-axon tracing studies have shown that virtually all components of primate basal ganglia are composed of different types of neurons endowed with a highly collateralized axon (see reviews by Parent et al, 2000, andParent, 2002). By virtue of its highly patterned efferent projection system, the CM/Pf complex should be considered as an integral part of this widely distributed neuronal system.…”

The mode of action of electrical high frequency stimulation

“…The GABAergic GP med projection neurons send their axons to the ventral tier thalamic nuclei and to the PPN; some of these GP med "motor" neurons additionally project to the CM/Pf thalamic complex [27]. The axons of other GP med neurons, termed "limbic" neurons by Parent and Parent (2002), arborize principally within the lateral habenular nucleus (LHb) with some collaterals to the anterior thalamic nuclei.…”

“…The axons of other GP med neurons, termed "limbic" neurons by Parent and Parent (2002), arborize principally within the lateral habenular nucleus (LHb) with some collaterals to the anterior thalamic nuclei. Afferents to the GP med include the GABAergic direct striato-pallidal monosynaptic pathway and the glutamatergic subthalamo-pallidal part of the indirect polysynaptic pathway.…”

“…Afferents to the GP med include the GABAergic direct striato-pallidal monosynaptic pathway and the glutamatergic subthalamo-pallidal part of the indirect polysynaptic pathway. In addition, a majority of GABAergic GP lat efferents have been shown to project through the GP med en route to the STN [27,28]. According to the literature, HFS of various GP med targets may induce different and even contrary clinical effects.…”