Abstract

BackgroundThe afferent projections of the striatum (caudate nucleus and putamen) are segregated in three territories: associative, sensorimotor and limbic. Striatal interneurons are in part responsible for the integration of these different types of information. Among them, GABAergic interneurons are the most abundant, and can be sorted in three populations according to their content in the calcium binding proteins calretinin (CR), parvalbumin (PV) and calbindin (CB). Conversely, striatal dopaminergic cells (whose role as interneurons is still unclear) are scarce. This study aims to analyze the interneuron distribution in the striatal functional territories, as well as their organization regarding to the striosomal compartment.Methodology/Principal FindingsWe used immunohistochemical methods to visualize CR, PV, CB and tyrosine hydroxylase (TH) positive striatal neurons. The interneuronal distribution was assessed by stereological methods applied to every striatal functional territory. Considering the four cell groups altogether, their density was higher in the associative (2120±91 cells/mm3) than in the sensorimotor (959±47 cells/mm3) or limbic (633±119 cells/mm3) territories. CB- and TH-immunoreactive(-ir) cells were distributed rather homogeneously in the three striatal territories. However, the density of CR and PV interneurons were more abundant in the associative and sensorimotor striatum, respectively. Regarding to their compartmental organization, CR-ir interneurons were frequently found in the border between compartments in the associative and sensorimotor territories, and CB-ir interneurons abounded at the striosome/matrix border in the sensorimotor domain.Conclusions/SignificanceThe present study demonstrates that the architecture of the human striatum in terms of its interneuron composition varies in its three functional territories. Furthermore, our data highlight the importance of CR-ir striatal interneurons in the integration of associative information, and the selective role of PV-ir interneurons in the motor territory. On the other hand, the low density of dopaminergic cells casts doubts about their role in the normal human striatum.

Highlights

  • The basal ganglia are considered an important subcortical center for the integration and control of many high level cognitive [1], motor [2] and limbic [3] processes

  • The present study aims to seek for possible variations in the distribution of the different populations of GABAergic interneurons (CR, PV- and CB-ir) and the tyrosine hydroxylase (TH-ir) cells with respect to the various functional territories and compartments of the human striatum

  • The present study is intended to clarify the main anatomical and topographical features of the GABAergic interneurons and dopaminergic cells in the human striatum, as a necessary step to understand the role of these neurons in striatal functioning

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Summary

Introduction

The basal ganglia are considered an important subcortical center for the integration and control of many high level cognitive [1], motor [2] and limbic [3] processes. It is well known that the striatum of primates (caudate nucleus, CN, and putamen, Put) receives associative, motor and limbic projections in different territories segregated throughout its whole extension. In order to achieve a proper holistic response to certain stimuli, the neural information that reaches the various striatal territories must be integrated at two different levels: within each ‘channel’, and between them. Descriptive analyses about the actual presence of the different types of neurons in the human striatum are scarce [12,13,14,15,16] and, to our knowledge, only our group has included the three functional territories in the whole extension of the CN and Put in previous reports [17,18]. The afferent projections of the striatum (caudate nucleus and putamen) are segregated in three territories: associative, sensorimotor and limbic. Striatal interneurons are in part responsible for the integration of these different types of information. This study aims to analyze the interneuron distribution in the striatal functional territories, as well as their organization regarding to the striosomal compartment

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