Morphology and classification of large neurons in the adult human dentate nucleus: A qualitative and quantitative analysis of 2D images

Abstract

The dentate nucleus represents the most lateral of the four cerebellar nuclei that serve as major relay centres for fibres coming from the cerebellar cortex. Although many relevant findings regarding to the structure, neuronal morphology and cytoarchitectural development of the dentate nucleus have been presented so far, very little quantitative information has been collected on the types of large neurons in the human dentate nucleus. In the present study we qualitatively analyze our sample of large neurons according to their morphology and topology, and classify these cells into four types. Then, we quantify the morphology of such cell types taking into account seven morphometric parameters which describe the main properties of the cell soma, dendritic field and dendrite arborization. By performing appropriate statistics we prove out our classification of the large dentate neurons in the adult human. To the best of our knowledge, this study represents the first attempt of quantitative analysis of morphology and classification of the large neurons in the adult human dentate nucleus.

Introduction

The dentate nucleus, the largest and phylogenetically most recent of the cerebellar nuclei lying in the cerebellar white matter, plays a role as major relay centre between the cortex and the other part of the brain. It receives its afferents from the premotor cortex and supplementary motor cortex (via the pontocerebellar system) and its efferents project via the superior cerebellar peduncle through the red nucleus to the ventrolateral thalamus (crossing over at the pontomesencephalic junction). It is responsible for the planning, initiation and control of volitional movements (Leiner et al., 1986, Ito, 1993, Mathiak et al., 2002).

In view of its functional significance and critical role in motor control, very little information is collected on the neuronal types that constitute this nucleus. One of the earliest descriptions of neurons in the human dentate nucleus can be found in Saccozzi's (1887) and Lugaro's (1895) Golgi studies of the neonatal human cerebellum. They divided the cells of the dentate nucleus into two groups—the large and small cells. Since the neonate is an infant from birth to 4 weeks of age, and the human dentate nucleus has a protracted development period, changing dramatically in size and shape as well as in its neuronal composition (Mihajlovic and Zecevic, 1986, Wadhwa and Bijlani, 1988, Hayaran et al., 1992b), whole period of prenatal cytoarchitectonical development of the human dentate nucleus and almost the whole postnatal developmental period remain unknown. Yet, recent descriptions offer some new data concerning the neuronal morphology of the dentate nucleus at various gestational ages (Verbitzkaya, 1969, Rakic and Sidman, 1970, Mihajlovic and Zecevic, 1986, Zečević et al., 1986, Yamaguchi et al., 1989, Hayaran et al., 1991, Hayaran et al., 1992a, Hayaran et al., 1992b, Yamaguchi and Goto, 1997) and early postnatal ages (Mihajlovic and Zecevic, 1986, Zečević et al., 1986, Wadhwa and Bijlani, 1988).

In the early period of gestation, the neurons of the human dentate nucleus are similar in shape and form, being mainly bipolar (Mihajlovic and Zecevic, 1986, Zečević et al., 1986, Hayaran et al., 1992a). The initial phase of neuronal maturation involves a transformation from bipolar to various forms of multipolar cells (Wadhwa and Bijlani, 1988). Working on different aspects of cytology and prenatal organization of cells of the human dentate nucleus. Mihajlovic and Zecevic (1986) and Zečević et al. (1986) have proved that the class of large neurons of the dentate nucleus could be further subdivided into four types according to their soma size and dendritic arborization. A similar classification has been used by Hayaran et al. (1992a) in their study on the cytoarchitectural development of the human dentate nucleus. Reporting on Golgi impregnated adult human dentate nucleus, Braak and Braak (1983) documented the presence of two cell types: large principal neurons and small local circuit neurons. No attempt was made by these authors to classify the dentate neurons on the basis of their morphology. To the best of our knowledge, there is no further Golgi study on cell classification of the dentate nucleus in the adult human. The morphology of the dentate nucleus in the adult human has also considered as single case (Mihajlovic and Zecevic, 1986, Zečević et al., 1986, Yamaguchi et al., 1989, Yamaguchi and Goto, 1997).

We undertook the present study with the aim to analyze features of the large neurons in the adult human dentate nucleus and quantify their morphology and topology. For that purpose, we qualitatively classified, at first, our sample of large neurons according to the shape of the cell body, dendritic arborization pattern and their location within the dentate nucleus. In order to test quantitatively our qualitative classification, we counted for all neurons seven morphometric parameters which describe quantitatively the main qualitative properties of the neurons. By performing the appropriate statistical analysis, our classification scheme of large cells in the human dentate nucleus was investigated.