Sensory Input and Behavior
Sex Differences in the Vomeronasal System

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Abstract

In the early eighties we found sex differences in the vomeronasal organ (VNO) and hypothesized that the vomeronasal system (VNS), a complex neural network involved in the control of reproductive behavior, might be sexually dimorphic. At that time sex differences had already been described for some structures that receive VNO input, such as the medial amygdala, the medial preoptic area, the ventromedial hypothalamic nucleus, and the ventral region of the premammillary nucleus. Since then, we have shown sex differences in the accessory olfactory bulb (AOB), the bed nucleus of the accessory olfactory tract (BAOT), and the bed nucleus of the stria terminalis (BST). When new VNS connections were found, all of them ended in nuclei that present sex differences. In general, sex differences in the olfactory system show two morphological patterns: one in which males present greater morphological measures than females, and just the opposite. To explain the morphometric measures of males in the latter, it has been hypothesized that androgens serve as inhibitors. Our work on the involvement of the GABAA receptor in the development of AOB and maternal behavior sex differences also suggests that neonatal changes in neuronal membrane permeability to the ion Cl differences. This might be the first animal model to help us to understand the situation in which human genetic and gonadal sex do not agree with brain and behavioral sex. Finally, we stress that sex differences in the VNS constitute a neurofunctional model for understanding sex differences in reproductive behaviors.

Introduction

The concept of a dual olfactory system (DOS) 66, 83, 93 refers to the widespread existence of two morphologically and functionally different olfactory systems in the vertebrate species. These are the main olfactory system (MOS) and the accessory olfactory system, or vomeronasal system (VNS).

At the beginning of the past century, the Danish surgeon Jacobson found a small structure in the nasal septum of mammals that probably serves as an olfactory organ. This structure differed from the olfactory mucosa and it was named Jacobson’s organ, or the vomeronasal organ [94]. The rodentia order shows a well-developed differentiated vomeronasal organ (VNO) 2, 94. This is especially the case in the muride and cricetidae families. The works of McCotter [52] and Herrick [38] have shown that the VNO fibers, or vomeronasal nerve (vn), reach the accessory olfactory bulb, which then projects fibers to the amygdala.

In 1953 Allison [2] proposed the existence of the cortical and the subcortical olfactory systems. In this description, the former included fibers from the lateral olfactory tract (lo), which ended cortically in the pyriform cortex (Pir), anterior olfactory nucleus (AO), olfactory tubercle (Tu), and corticomedial amygdaloid complex. The latter system consisted of projections that were assumed to end in the central amygdaloid nucleus (Ce) and bed nucleus of the stria terminalis (BST). Several years latter, however, this description of connectivity for the subcortical system was shown to be partially incorrect.

In 1970 Winans and Scalia [93] demonstrated for the first time that in the rabbit the posteromedial cortical amygdaloid nucleus (PMCo) and medial nucleus of the amygdala (Me) receive projections from the AOB. Moreover, they noticed that projections from the main olfactory bulb (MOB) ended differently from those originating in the AOB. That is, the MOB projections terminated in the prepyriform cortex and Tu. They also found that the terminals of these fibers were limited to the anterolateral portion of the cortical nucleus of the amygdala. Later, this pattern of connectivity was confirmed for several more species 15, 23, 82, 84.

The MOS and the VNS have different neural pathways for hypothalamic projections. Input coming from the olfactory mucosa and MOB reaches the lateral preoptic and hypothalamic areas, and it seems to run through the lateral olfactory tract (lo) to its nucleus, the Tu, the anterior and posterolateral cortical amygdaloid area, and the anterior amygdala. It takes the ventral amygdalofugal pathway from these areas to the lateral hypothalamus 14, 37, 83.

The VNS input reaches the medial preoptic area (MPA) and ventromedial hypothalamus (VMH). VNO bipolar neurons reach the AOB, which projects to the vomeronasal amygdala (Me and MPCo nuclei) by way of the accessory olfactory tract (aot). A bundle of fibers from the aot synapses with a small group of neurons that form the bed nucleus of the accesory olfactory tract (BAOT), and another bundle reaches the posterior position of the medial division of the BST (BSTMP) via the stria terminalis (st). The BST and the vomeronasal amygdala then project to the PMA-AH continuum, VMH, and ventral premammillary nucleus by way of the st. This pattern of connectivity has been observed in several species 6, 15, 22, 41, 42, 83, 85. However, this VNS picture might be more complicated because the MPA seems to receive direct input from the VNO [43]. Using anterograde tract tracing techniques, Smithson et al. [87] have recently shown that there might be a direct projection from the AOB to the supraoptic nucleus (SO) in the rat.

The pattern of reciprocal connectivity uniting VNS structures is also different from that of the MOS 12, 13, 23, 24, 41, 65, 72, 92. However, as pointed out by Licht and Meredith [45], we should be aware of possible relationships between the VNS and MOS, because functional convergence at least in the hamster amygdala has been reported [45].

Twenty years ago Power and Winans [64] showed that the VNO has a functional role in the copulatory behavior of hamsters. Since that time reports have indicated that the VNS plays an important role in the perception of chemical stimuli of a reproductive nature. It mediates the action of pheromones, which are involved in eliciting and maintaining masculine and feminine sexual behavior, and primer pheromone mechanisms, which affect gestation, the estrous cycle, and puberty. In addition it is involved in agression, social recognition, and parental and neonatal behaviors 36, 94, 95. Recently, it has been shown that most humans have a pair of VNOs. Studies performed include light and electron microscopy as well as immunohistochemistry and electrophysiological techniques 56, 57.

Section snippets

Sex Differences in the Vomeronasal System

In the early eighties we investigated sex differences in the VNO. We found that, neonatally, gonadal steroids develop a sexually dimorphic VNO in the rat [74]. The overall volume, neuroepithelial volume, and number of bipolar neurons are all larger in males. These sex differences are abolished and inverted when males are orchidectomized and females are androgenized on the day of birth (D1). Androgenized females present greater morphometric measures than control females and similar measures to

Hormonal Control of the Development of Sex Differences in the VNS

As mentioned above, sex differences in the rat CNS show two morphological patterns, one in which males present larger volumes and numbers of neurons than females and the exact opposite, in which females show larger volumes and greater numbers of neurons than males 35, 76. Most of the structures of the vomeronasal pathway (VNO, AOB, BAOT, Me, BSTMP, MPA-AH, SO, VMH) belong to the former, while others that also receive vomeronasal input (BSTMA, ARC) follow the latter.

The mechanisms promoting

Acknowledgements

This study was funded by DGCYT grants PB93-0291-C03-01 (A.G) and PB95-0060-C02-01 (S.S). We would like to thank M. F. Litzer, C. Garcı́a-Malo de Molina, R. Sánchez, and A. Marcos for their editorial help.

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