Possible pathways through which neurons of the shell of the nucleus accumbens influence the outflow of the core of the nucleus accumbens

Abstract

The nucleus accumbens (Acb), a major sector of the ventral striatum, is considered to be an integral part of the striatal complex. The Acb has been shown to be composed of two subdivisions, core and shell, which are distinguishable in several aspects, suggesting that these two subdivisions play different functional roles. The aim of this study was to identify pathways of the efferents of the shell of the Acb to influence the outflow of the core of the Acb. Potential disynaptic projections of the shell to the core of the Acb were investigated in chloral hydrate-anesthetized male Sprague–Dawley rats. Following ipsilateral injections of biotinylated dextran amine (BDA) into the shell of the Acb and cholera toxin B subunit (CT-B) into the core, strong overlapping distributions of BDA-labeled terminals and CT-B-labeled neuronal cell somata were found in the medial part of the ventral tegmental area, medial part of the lateral hypothalamic area, and dorsolateral part of the basolateral amygdaloid nucleus. The significance of multiple sites of relay between the efferents of the shell and the afferents of the core of the Acb at different levels of the neuraxis may be related to the functional specificity of each relay site.

Introduction

The nucleus accumbens (Acb), a major sector of the ventral striatum, is directly continuous with the main dorsal part of the striatum (the caudate-putamen) and it is generally agreed that this nucleus is an integral part of the striatal complex [1]. The Acb has been shown to be composed of two subdivisions, core and shell, which are distinguishable based on cytoarchitecture [2], distributions of various neuroactive substances and receptors [3], [4], [5], [6], [7], [8], [9], synaptic organization [10], as well as pharmacological [11] and physiological properties [12], [13]. Both the core and the shell of the Acb have striatal characteristics histologically as well as in their connection patterns. The shell, however, has a number of features atypical for a striatal structure, which are reminiscent of the extended amygdala [5], [14]. For example, the shell is likely to be most extensively involved in emotions and limbic-related processes based on extensive connections with limbic circuits [1], [15] and is of special interest in relation to depression as well as certain forms of stress [16], [17].

The rather massive projections from the shell and the core of the Acb are those to the substantia nigra and the ventral tegmental area as well as the pallidal areas, including the ventral pallidum and the entopeduncular nucleus, with a distinct topography. For example, the shell primarily innervates the ventral tegmental area, especially its medial part, whereas the core projection involves significantly the lateral part of the ventral tegmental area as well as the whole mediolateral extent of the substantia nigra pars compacta [5], [18], [19], [20], [21], [22]. Since the substantia nigra pars compacta contains A9 dopaminergic cell groups which in turn project to the dorsal striatum, an important concept that the dorsal striatal complex might be modulated, presumably via dopamine circuits, by the core of the Acb was previously suggested [18], [23]. Considering the importance of the mesolimbic dopamine circuits from the ventral tegmental area to the Acb in behavior [15], [24], [25], [26], a critical question arising here is whether the outflow of the ‘limbic’ part of the Acb, i.e. the shell, is also in a position to influence neurons in another mesencephalic dopaminergic area, i.e. the ventral tegmental area [27], which is the origin of the mesolimbic dopamine system projecting to the Acb, primarily the core subregion.

In the present investigation, we sought to determine the potential substrates for modulatory interactions in the ventral tegmental area between the core and the shell of the rat Acb. To address this issue, an anterograde tracer and a retrograde tracer were injected into the shell and the core of the Acb, respectively, in the same animals and the relationship between the efferent projection fibers of the Acb shell and the afferents of the Acb core was studied. In addition to the ventral tegmental area, attention was paid also to a search for additional potential sites of the shell–core interactions.