Elsevier

Brain Research Reviews

Volume 38, Issues 1–2, December 2001, Pages 192-246
Brain Research Reviews

Interactive review
Topography of projections from amygdala to bed nuclei of the stria terminalis

https://doi.org/10.1016/S0165-0173(01)00079-0Get rights and content

Abstract

A collection of 125 PHAL experiments in the rat has been analyzed to characterize the organization of projections from each amygdalar cell group (except the nucleus of the lateral olfactory tract) to the bed nuclei of the stria terminalis, which surround the crossing of the anterior commissure. The results suggest three organizing principles of these connections. First, the central nucleus, and certain other amygdalar cell groups associated with the main olfactory system, innervate preferentially various parts of the lateral and medial halves of the bed nuclear anterior division, and these projections travel via both the stria terminalis and ansa peduncularis (ventral pathway). Second, in contrast, the medial nucleus, and the rest of the amygdalar cell groups associated with the accessory and main olfactory systems innervate preferentially the posterior division, and the medial half of the anterior division, of the bed nuclei. And third, the lateral and anterior basolateral nuclei of the amygdala (associated with the frontotemporal association cortical system) do not project significantly to the bed nuclei. For comparison, inputs to the bed nuclei from the ventral subiculum, infralimbic area, and endopiriform nucleus are also described. The functional significance of these projections is discussed with reference to what is known about the output of the bed nuclei.

Introduction

The cerebral hemisphere gray matter that surrounds the stria terminals — from the temporal pole caudally to the base of the olfactory peduncle rostrally — was defined originally by J.B. Johnston in 1923 as the bed of the stria terminalis [45]. The temporal end of Johnston’s bed of the stria terminalis is now regarded as the main part of the amygdala, and only a few neurons can be traced along the body of the stria terminalis, in the rat at least [54], [90]. In contrast, the rostral end of Johnston’s bed of the stria terminalis, which lies just ventral to the lateral septal nucleus and just dorsal to the preoptic region of the hypothalamus, surrounding the crossing of the anterior commissure, has come to be referred to as the bed nuclei (or bed nucleus) of the stria terminalis (BST) in mammals.

A vast physiological literature indicates that the amygdala can influence profoundly a variety of visceromotor responses as well as the expression of instinctive and conditioned behaviors with a motivational and/or emotional component (for reviews see [1], [23], [33], [50], [53], [60], [78], [107]). In a companion paper [74] we have reviewed how these influences could be mediated by projections from the amygdala directly to the hypothalamus and lower brainstem, as well as by projections from the amygdala to other parts of the cerebral cortex including the hippocampus and medial prefrontal region — which in turn project directly or indirectly via the basal ganglia/cerebral nuclei/striatopallidal system to the hypothalamus and lower brainstem. Here we consider in detail the organization of yet another potential route, via the BST, which are known to project massively to the hypothalamus and lower brainstem [29], [30], [31], [42], [105].

It was known in a general way from normal [45] and experimental degeneration (e.g., [20], [25], [28], [40], [54]) material that the amygdala provides a major input to the BST. However, it was the pioneering autoradiographic analysis of Krettek and Price [51] that showed how individual cell groups associated with the amygdala project in a topographically ordered way upon the BST, which they parcelled into basic medial and lateral divisions. They concluded that the lateral division of the BST is innervated by the central and basolateral nuclei of the amygdala, that the medial division of the BST is innervated by the medial and posterior cortical nuclei and the amygdalo–hippocampal area (posterior nucleus), and that a central zone of the BST (which includes parts of both the medial and lateral divisions) is innervated by the basomedial nucleus. Several years later Weller and Smith arrived at similar conclusions based on the HRP retrograde tracer method [115].

In the two decades following this seminal work a great deal has been learned about the structural, and presumably functional, organization of the BST. From our own perspective, the most important advance was the basic division in 1989 of the BST into anterior and posterior (rather than medial and lateral) components and the recognition of some 20 distinct cell groups within them, based on a combination of cyto- and chemoarchitectonic criteria [47], [48]. Since then, accumulating evidence indicates that at least some of the cell groups we recognized are innervated by different amygdalar cell groups [12], [14], [18], [73], [75], [76], [97], and generate distinct projection patterns [29], [30], [31], [63], [80], [95]. Presumably, an even more fine-grained analysis of connections associated with individual BST cell groups will help clarify functions ascribed to the BST as a whole, including neuroendocrine and autonomic responses [22], [36], [55], [98], [99], stress responses (e.g., [16], [24], [32], [41]), responses to withdrawal from drugs of abuse [6], salt appetite [44], and the expression of social behaviors [80].

Since the last comprehensive examination of amygdala to BST projections [51], the PHAL method for anterograde tracing has been established. It has three main advantages over the autoradiographic method. First, it is more sensitive; second, even more circumscribed, easy to delineate injection sites can be produced; and third and of primary importance, the morphology of labeled axons is observed with the clarity of Golgi impregnations; sometimes ambiguous patterns of silver grains need not be interpreted. The data presented here is fundamentally important for interpreting the results of our ongoing analysis of projections from each of the cell groups currently recognized in the BST.

Section snippets

Materials and methods

A total of 125 PHAL experiments, each with an injection site involving one part of the amygdala or another, were available for this analysis. The overall projection pattern labeled in many of these experiments has already been described in detail [12], [14], [73], [75], [76], along with exactly how the histological material was produced. Additional experiments with injections in other parts of the amygdala were also available, as indicated below, and were prepared in the same way, as were

Overview of amygdalar and BST structural organization

There is still some disagreement about the exact parcelling and nomenclature of the mammalian amygdalar region in the literature, which is reviewed in the companion paper [74]. The current version of our own structural model [74], [101], [107] views amygdalar cell groups as components of four cortico-striatopallidal functional systems: accessory olfactory, main olfactory, autonomic, and frontotemporal association (Fig. 1).

As mentioned in Section 1, Krettek and Price [51], [52] used a basic

Projections from amygdala to BST

Before exploring the details of this massive projection system it is useful to consider an overview of the results (Fig. 1). To begin with, axons from the amygdala reach the BST via two distinct pathways, the stria terminalis (dorsal pathway) and the ansa peduncularis (ventral pathway). Amygdalar cell groups associated with various functional systems innervate distinctive regions of the BST via the stria terminalis and/or ansa peduncularis. The central nucleus, which can be thought of as a

Projections from other cerebral regions to BST

We have just seen that not all cell groups associated with the amygdala project to the BST, and conversely it should be borne in mind that other parts of the cerebral hemispheres also project to the BST. Because we have very useful PHAL injections in several of these extra-amygdalar sites, their projections to the BST will be considered briefly for the sake of completeness.

Discussion

The results presented above indicate that amygdalar cell groups associated with particular functional systems project upon the BST in highly organized ways (Fig. 3). Overall, the autonomic part of the amygdala innervates the anterior BST; accessory olfactory parts of the amygdala innervate the posterior BST and medial group of the anterior BST; and some parts of the main olfactory amygdala project to the BST like the autonomic part, whereas other parts of the main olfactory amygdala project to

Acknowledgements

We deeply appreciate the invaluable contributions of Newton Canteras to our research on the amygdala. The experimental work was supported in part by NINDS grant NS16686.

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