Community Research and Development Information Service - CORDIS



Project ID: 303785
Funded under: FP7-PEOPLE
Country: Israel

Final Report Summary - GNRH & REPRODUCTION (Role of GnRH neurons in Reproductive Behavior and Physiology)

This project was designed to explore how chemosensory stimuli modulate neuronal activity in central brain targets of the vomeronasal system, in the context of male mouse reproductive behaviors. The end goal of this project was to record the activity of genetically identified hypothalamic populations in response to various female chemical cues. One of the preliminary stages of the project involved an initial characterization of various female cues, and their ability to elicit responses in earlier stages of the vomeronasal system. As it often, during this initial stage we had made some interesting observations that led us to spend more time than initially planned on this initial stage.
Specifically, we tested the responses of neurons in the first brain processing stage of the vomeronasal system to three types of female secretions: urine, saliva, and vaginal secretions. While urine has been intensively investigated as a stimulus source, much less was known about the capacity of the other two stimuli to convey socially relevant information. One of the conclusions of our study is that all three stimulus sources can provide information about a female mouse’s strain and reproductive state (i.e. whether she is in estrus or not). The significance of this finding is that it expands the set of known natural stimuli that are detected by the vomeronasal system. However, our analysis also highlighted the complexity of extracting behaviorally relevant information from natural chemical secretions, which are typically composed of a very large number of individual components. A key challenge faced by the nervous system is that these natural chemical stimuli may be modulated by various sources of variability. Factors such as stimulus dilution, stimulus sources (e.g. is it saliva or urine?), and the interaction between different trait can modulate the composition of these chemical cues in non-trivial ways. To explore how information can actually be extracted despite these potential confounds, we designed a set of experiments in which we measured the responses of accessory olfactory bulb neurons to a stimulus set from female mice, which represented all these sources of variability. The major conclusion from our study, which has been published in PLOS computational biology, is that information about socially relevant traits is represented using a combinatorial code of AOB neurons. More specifically, the responses of individual neurons are ambiguous with respect to specific traits (an individual’s strain or reproductive state), but the ambiguity can be resolved by using linear classifiers that accept as inputs a small number of neurons. The results from these experiments led to more general insights on the complexity of chemosensory stimulus detection, and the potential solutions under various scenarios. These insights have been published as a Hypothesis & Theory paper in Frontiers in Neuroscience.
Funding for this project has also been important in the context of three collaborative efforts, all closely related to the central via the theme of information processing in the accessory olfactory system. One of these projects highlights the role of urinary acidity in modulating vomeronasal responses and in conveying socially relevant information. In another study, we characterized the bursting activity of accessory olfactory bulb neurons. Both of these studies were performed as part of a collaboration with our German colleagues (Prof. Spehr’s group in Aachen) and published in the Journal of Neuroscience. In another collaborative effort, performed with Israeli colleagues Jerusalem and Haifa (Profs. Yosi Yarom, and Shlomo Wagner) and published in PLOS Biology we focused on the slow temporal dynamics of accessory olfactory responses. Altogether then, we have authored and co-authored several manuscripts with the common theme of information processing in the vomeronasal system, three of which are directly related to communication of social information via the system.
In parallel to these lines of research, we have also made significant progress related to the end goal of the CIG project, namely, to record from genetically identified hypothalamic populations. We have established all the required elements (involving software, hardware, genetic mouse models) and have been conducting these experiments for more than 2 years. After some initial failures to record from GnRH neurons in the hypothalamus, due most likely to their small number and scattered locations, we have focused instead on other hypothalamic neuronal populations that are larger, and hence easier to target. We have been successful in those experiments, and are in the process of assessing the responses of these genetically identified neurons to controlled delivery of socially relevant chemosensory stimuli.

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