Anatomical and electrophysiological study of the vomeronasal circuits: amygdaloid response to odours and pheromones

Rodents detect information concerning the world around them mainly through two chemosensory systems: the olfactory and the vomeronasal systems. In order to develop an appropriate behavioural response to their environment, these systems exhibit both functional and physiological convergence. Further understanding of the organization and function of the olfactory systems would allow us to comprehend how their information is integrated in the brain. In a first approach we performed a thorough analysis of the connections of key structures involved in the processing of vomeronasal information: the medial (Me) and the posteromedial cortical (PMCo) amygdaloid nucleus. Then, we enquire the population activity elicited by olfactory and vomeronasal stimuli in three main structures of the vomeronasal system: the accessory olfactory bulb (AOB), Me and PMCo; and, simultaneously, the activity in the main olfactory bulb (MOB). This will allow us to investigate both the neural circuitry processing olfactory and vomeronasal information and the basic principles of integration of these stimuli. The PMCo is the unique cortical target of the AOB and should therefore be considered the primary vomeronasal cortex. It coordinates the neural processing of vomeronasal cues, as it receives information from and projects back to each of the structures of the vomeronasal system and shows significant interconnections with the main olfactory system. Also, through its projections to the Me, the ventral hippocampus and the ventral striatum, PMCo directs behavioural responses and contributes to the spatial map of the chemical environment. The Me coordinates the behavioural response to olfactory and vomeronasal cues. It shows a high connectivity among its subdivisions, with the other nuclei of the chemosensory amygdala and with structures of the olfactory system (especially the anterior Me), thus suggesting that the information from these systems is subjected to a complex intrinsic processing before being relayed to other structures. Aside from these, the main efferences of the Me are the bed nucleus of the stria terminalis (BST) and the hypothalamus, through which the subdivisions of the Me mediate different behavioural responses. The anterior and posteroventral subdivisions of the Me are mainly involved in defensive behaviours through its connections with the medial posterointermediate BST and the defensive hypothalamic circuit; and, although less dense, they also innervate reproductive-related nuclei perhaps controling the inhibition of sexual behaviours. The posterodorsal subdivision of the Me mediates reproductive behaviours through its projections to the medial posteromedial BST and the hypothalamic reproductive circuit, although some projections to defensive-related nuclei also exist. The emergence of a coherent behaviour relies on the communication between brain regions that are functionally and anatomically specialised. Communication between the AOB and the other nuclei is mediated by theta oscillations, as the AOB shows high phase coupling with the MOB, Me and PMCo. Furthermore, the circuit responds with different oscillatory rhythms depending on the perceived stimulus. The exploration of a neutral stimulus (absence of vomeronasal cues) induces a prominent theta activity with a peak at 4 - 6 Hz in both olfactory bulbs, the Me and the PMCo; while conspecific-derived stimuli (containing both olfactory and vomeronasal cues) induce oscillatory activity at ~ 7 Hz. The correlated activation of the bulbs suggests a coupling between the stimuli internalization in the nasal cavity (sniffing) and the vomeronasal pumping. Moreover, the Me shows a characteristic theta peak elicited by male-soiled bedding and the PMCo shows a similar theta peak in response to female-derived stimuli, thus indicating a differential processing within the amygdala related to the sex of the conspecific. During the exploration epochs, the AOB and the amygdaloid nuclei show fast-gamma frequency segments (90 - 120 Hz) modulated by the theta waves in AOB; whereas the MOB evidences an increase in the high-gamma band (60 - 80 Hz) that were also modulated by the theta in AOB. Thus, particular theta-gamma patterns in the olfactory network modulate the integration of chemosensory information in the amygdala, allowing the selection of an appropriate behaviour. In summary, the present results show the different levels of convergence of the olfactory and vomeronasal information. We describe the wiring of the amygdaloid structures receiving information from the olfactory bulbs and transferring it to hypothalamic and striatal targets. The different nodes show coupled activity and effective communication, that allow the system to work together as a network for the integration and response to chemosensory cues.