ReviewA field guide to the anterior olfactory nucleus (cortex)
Introduction
Research on the organization and function of the mammalian olfactory system has accelerated rapidly in the past decade, undoubtedly sparked by Linda Buck and Richard Axel's [29] groundbreaking work on the molecular biology of the olfactory receptor that led to their 2004 Nobel Prize. However, a thorough understanding of the system is impeded by the relative paucity of information concerning the role of cortical areas in processing olfactory information. Perhaps nowhere is this more apparent than in the anterior olfactory nucleus (AON). This structure is heavily interconnected with both the olfactory bulb and the primary olfactory cortex and displays a large number of interhemispheric projections. Yet, despite the region's obvious importance in olfactory information processing, the structure, organization and function of the AON remain largely unknown.
In the present paper, we attempt to bring together the widely dispersed literature regarding the AON. We begin with a description of the region in the mammalian brain and an effort to clarify the often divergent nomenclature that has been used to describe it. Next, we consider differences in cytoarchitecture and innervation patterns found among the AON's subregions. We conclude with a discussion of the area's function, which undoubtedly is much more complicated than is often portrayed. It is our hope that assembling this information will promote further investigation into the organization and function of this key processing point for olfactory information.
Section snippets
Where is the anterior olfactory nucleus/cortex?
In most mammalian species, the olfactory bulb is the rostral-most portion of the telencephalon (indeed, the entire brain), located just behind (or above) the nasal cavity (Fig. 1). The caudal boundary of the olfactory bulb is marked by a small groove variously known as the fissure circularis rhinencephali [95], [128], fissure prima [108] or fissure circularis [255]. The indentation is oriented obliquely: the medial side is caudal with respect to the lateral (Fig. 2, [3], Fig. 3). The area
Anterior olfactory nucleus or anterior olfactory cortex?
What one calls the region is, of course, dependent on how one defines the terms “nucleus” and “cortex.” Herrick [94], [95], [96] in his work with amphibians and opossums was responsible for naming the region the “anterior olfactory nucleus.” Pigache [178] also agreed that it was a nuclear area. According to him, “To be classified as a cortex a region must be clearly divisible into a minimum of at least three tangential layers, the most superficial being plexiform, connected by a regular lattice
Are there subdivisions?
Based on Nissl stains, the AON has been divided into two basic zones: “pars externa,” a thin ring of cells that encircles the rostral end of the olfactory peduncle, and the remainder, sometimes referred to as “pars cruralis” [178] or “pars principalis” [242]. Pigache's [178] chapter contains an interesting description of the early nomenclature of the region. The structure can be found behind the olfactory bulb in all vertebrates. Since in many primates the bulb is located at the end of a long
Cell morphology
The AON is often characterized as a region populated primarily by pyramidal cells (e.g., [233]; see cells a–c in Fig. 5). The cells are similar to neocortical pyramidal cells with a thick apical dendrite, several basal dendrites and dense dendritic spines. However, variant morphologies have also been described. For example, Fig. 12 in the paper by Haberly and Price [83] depicts cells from pars lateralis with multiple apical branches. Valverde et al. [242] indicated that the deep pyramidal cells
Neurochemical phenotypes
A further way to assess the diversity of cell types in the AON is to catalog the range of neurochemical phenotypes resident in the area. Once again, if the AON is indeed simply a “relay,” it might be expected that the structure consists primarily of glutamatergic pyramidal cells. On the contrary, several studies have demonstrated considerable diversity (see Table 1). For example, Garcia-Ojeda et al. ([73], [3], see also [12], [17]) reported that a subset of cells in all subdivisions of the AON
Other structures in the “olfactory peduncle”
The tenia tecta is the anterior terminus of a small column of cells extending from the hippocampus and over the top of the corpus callosum (where it is known as the indusium griseum). From the genu, the structure descends through the septal region as a zone often referred to as the anterior hippocampal rudiment (or anterior hippocampal extension, or dorsal tenia tecta) and into the medial aspect of the AON, where it can be confused with pars medialis [1], [83], [252]. A cell-free gap, visible
Projections from the olfactory bulb to the AON
Bulb organization has been carefully studied at many levels, and several general reviews are available [206], [207], [215], [219]. Here, we provide a brief overview to facilitate later discussion of the reciprocal innervation of OB and the AON.
Olfactory sensory neurons (OSNs) are found in the olfactory epithelium that lines the caudal third of the nasal cavity. The dendrites of the cells have cilia that extend into the apical mucous layer and house the receptors that recognize chemical motifs.
Backprojections from the AON to the olfactory bulb
Information about the projections from the AON to the bulb also is rudimentary. It has been suspected for over a hundred years that the left and right olfactory bulbs are connected via the anterior commissure, although Cajal's ([31], [1], [32]; see also [183]) early examination of the region wrongly suggested that the axons of mitral and tufted cells pass through the anterior commissure to innervate the contralateral bulb. Electrophysiological evidence also concluded that there were
Projections from the AON to piriform cortex
The piriform cortex is traditionally designated as “primary olfactory cortex” because it is the largest cortical recipient of afferent fibers from the olfactory bulb. However, this designation belies the associative nature of the region; in addition to projections from the OB, cells in piriform cortex receive input from an extensive autoassociative network and from many neocortical and subcortical areas [23], [81], [82], [101], [109], [135]. Indeed, it has been suggested that the piriform
Projections from piriform cortex to AON
Projections to the AON from piriform cortex are complex, and subregions within the AON have distinct connections. Following unilateral injections of HRP in the APC [82], the highest density of anterogradely labeled cells was found in pars lateralis in the ipsilateral hemisphere. In addition, many labeled cells were found in both pars dorsalis and pars ventroposterioralis.
Following injections of 3H-leucine in APC deep to the LOT, Luskin and Price [135] found a heavy projection to pars lateralis
Tenia tecta and dorsal peduncular cortex
Relatively little work has examined the projection pathways of these regions. Both Davis and Macrides [48] and Rehyer et al. [185] found that the ventral tenia tecta has a light ipsilateral projection to the deep granule cell layer of the ipsilateral olfactory bulb, but with a lighter projection than that seen from pars medialis. Topographic connections have been reported between the tenia tecta and the remainder of the AON [135], with injections of 3H-leucine in the inferior ventral tenia
Non-“olfactory system” projections into and out of the AON
Assessing the projections to the AON is complicated because these inputs have rarely been the focus of studies. As a result, much of the information is buried in reports of the broad projections of particular regions, and many of these studies do not report differential projections within the AON. Nevertheless, the available evidence demonstrates that there are rich projections that exhibit at least some regional specificity. Table 2 summarizes this information.
Development
3H-thymidine studies [19], [44] have demonstrated that AON cells are generated between embryonic day 15 and 21 in two distinct patterns in the rat. All divisions exhibit a caudal-to-rostral gradient of neurogenesis similar to that seen in the piriform cortex. A second superficial-to-deep gradient was also observed which contrasts with the “inside–out” sequence typical of cortical areas [19], [44]. Schwob and Price [205] reported that a clearly defined layer II emerges by embryonic day 19,
Physiology
There are very few electrophysiological studies that focus on the AON. Several early works, cited above, were designed to verify the contralateral projections of the structure and reported normative data on general properties such as axonal conduction velocities. Boulet et al. [22] recorded from 64 cells in pars ventralis and compared their activation patterns with mitral cells. They concluded that mitral cells were better at discriminating the 6 test odor stimuli, while the AON cells seemed
Summary and conclusions
In this review, we have tried to assemble the available information concerning the structure, organization and function of the AON. Every attempt has been made to thoroughly scour the literature for information, but undoubtedly some works have been overlooked. The authors regret any such omissions.
There have been few attempts to identify or model the function of the AON. One theory has been put forward by Haberly [81] as part of an effort to establish a theoretical framework for the overall
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