Double-bouquet cells in the monkey and human cerebral cortex with special reference to areas 17 and 18

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Abstract

The detailed microanatomical study of the human cerebral cortex began in 1899 with the experiments of Santiago Ramón y Cajal, who applied the Golgi method to define the structure of the visual, motor, auditory and olfactory cortex. In the first article of this series, he described a special type of interneuron in the visual cortex capable of exerting its influence in the vertical dimension. These neurons are now more commonly referred to as double-bouquet cells (DBCs). The DBCs are readily distinguished owing to their characteristic axons that give rise to tightly interwoven bundles of long, vertically oriented axonal collaterals resembling a horsetail (DBC horsetail). Nevertheless, the most striking characteristic of these neurons is that they are so numerous and regularly distributed that the DBC horsetails form a microcolumnar structure. In addition, DBCs establish hundreds of inhibitory synapses within a very narrow column of cortical tissue. These features have generated considerable interest in DBCs over recent years, principally among those researchers interested in the analysis of cortical circuits. In the present chapter, we shall discuss the morphology, synaptic connections and neurochemical features of DBCs that have been defined through the study of these cells in different cortical areas and species. We will mainly consider the immunocytochemical studies of DBCs that have been carried out in the visual cortex (areas 17 and 18) of human and macaque monkey. We will see that there are important differences in the morphology, number and distribution of DBC horsetails between areas 17 and 18 in the primate. This suggests important differences in the microcolumnar organization between these areas, the functional significance of which awaits detailed correlative physiological and microanatomical studies.

Introduction

The detailed study of the microanatomy of the primate visual cortex began with the studies of Santiago Ramón y Cajal in 1899. Using the Golgi method, he commenced a series of studies on the comparative structures of different functional regions of the human cerebral cortex (Cajal, 1899a, Cajal, 1899b, Cajal, 1899c, Cajal, 1900, Cajal, 1901; DeFelipe and Jones, 1988). The aim of Cajal and other authors at that time was to determine whether it was possible to explain functional specialization through structural specialization:

[…] for example, if an organizational detail is exclusively found or is particularly exaggerated in the visual cortex, we will be justified in suspecting that it has something to do with [cerebral visual function]. Conversely, if an anatomical detail is repeated similarly in all cortical regions, we will be justified in assuming that it is devoid of a specific functional significance and instead is of a more general [significance]

(Cajal, 1899b).

Cajal examined the visual cortex layer by layer (Fig. 1), producing beautiful and accurate drawings to illustrate the neuronal components of each layer and their possible connections (Fig. 2). The first article of these series of studies was a preliminary report that appeared in the Revista Ibero-Americana de Ciencias Médicas (Cajal, 1899a). In this article he described two new types of aspiny interneurons: a giant cell with a horizontal axon, which according to Cajal would be similar to the special cells of layer I or the Cajal–Retzius cells; and a small fusiform bitufted cell with a characteristic axon that is formed of small bundles, comparable to locks of hair [that were] so long that they extend through almost the whole thickness of the gray matter. This bitufted cell type was considered by Cajal as a special type of interneuron capable of exerting its function in the vertical dimension:

In some places, it can be seen that the small bundles of threads are applied to the [apical dendrites] and somata of a series of vertical pyramids, from which we think it very probable that the cells referred to are a special category of cells with a short axon, whose role would be to associate pyramids resident in different layers in the vertical direction

(Cajal, 1899a; DeFelipe and Jones, 1988).

However, instead of giving a different name to this particular neuronal type, Cajal used the term bitufted cell (células bipenachadas in Spanish, double-bouquet cell in French) to describe neurons with different dendritic and axonal morphologies (Cajal, 1899a, Cajal, 1899b, Cajal, 1899c, Cajal, 1900, Cajal, 1901, Cajal, (1909,1911); DeFelipe, 2002). After the studies of Cajal, these cells were virtually ignored until interest in the Golgi method resurged with the analysis of cortical microanatomy that was carried out in the 1960s and 1970s by a number of investigators (Sholl, 1956; Colonnier, 1966; Marin-Padilla, 1969; Szentágothai, 1969; Scheibel and Scheibel, 1970; Valverde, 1970; Lund, 1973; Jones, 1975). Because these cells did not have a particular name, they received different names, which generated some confusion in the literature. For example, Szentágothai referred to them as cells with horsetail-shaped axons, Jones as type 3 neurons, and Valverde as cells with axons forming vertical bundles (Szentágothai, (1973), Szentágothai, 1975; Jones, 1975; Valverde, 1978, Valverde, 1985), while along with other authors, we have preferred to apply the French term double-bouquet cell (DBC) specifically to those neurons whose axons form such vertical bundles, irrespective of their somato-dendritic morphology (DeFelipe, 2002). The axonal arbors of DBCs are generally termed DBC axonal bundles or horsetails owing to their resemblance to a horse's tail. Together with basket cells and chandelier cells, these neurons are currently considered as the three main types of inhibitory GABAergic interneurons that innervate pyramidal cells in the neocortex (Fig. 3). In this chapter, we shall discuss features of DBCs that have been identified in the study of these cells in different cortical areas and species. In particular, we will focus on the morphology and distribution of DBCs in the visual cortex (areas 17 and 18) of the human and macaque monkey.

Section snippets

General characteristics of DBCs

Using the Golgi method, DBCs have been identified in layers II and III of different areas of the cat, monkey, and human cortex (reviewed in Peters and Regidor, 1981; Fairén et al., 1984; DeFelipe, 2002). At present, DBCs are defined as interneurons with a somato-dendritic morphology that is either multipolar or bitufted, and whose axons give rise to tightly interwoven bundles of long vertically orientated axonal collaterals resembling a horsetail (DBC horsetail) that descends from layer II or

DBC horsetails in areas 17 and 18 of the macaque monkey and human

In general, the density and morphology of DBCs vary in different areas of the macaque and human neocortex (DeFelipe et al., 1999; Ballesteros-Yáñez et al., 2005). What follows is the description of DBC horsetails in areas 17 and 18 of both the macaque and human (Table 2).

Abbreviations

    DBCs

    double-bouquet cells

    DBC horsetails

    double-bouquet cell horsetails

    CB

    calbindin

    -ir

    immunoreactive

    SOM

    somatostatin

    TK

    tachykinin

Acknowledgments

This work was supported by the Spanish Ministry of Education and Science (Grant nos. BFI2003-02745 and BFI2003-01018 and a research fellowship to Inmaculada Ballesteros-Yáñez, AP 2001-0671) and the Comunidad de Madrid (Grant no. 08.5/0027/2001).

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