Section: Application Domains

Neuroendocrinology and Neuroscience

We are interested in the complex dynamical processes arising within neuroendocrine axes, with a special focus on the reproductive (hypothalamo-pituitary-gonadal) axis. This axis can be considered as the paragon of neuroendocrine axes, since it both concentrates all remarkable dynamics that can be exhibited by these axes and owns its unique specificities, as gonads are the only organs that host germ cells. Since, in neuroendocrine axes, neural systems are embedded within endocrine feedback loops and interact with peripheral organs, one also needs to get interested in the peripheral dynamics to be able to “close the loop” and account for the effect of peripheral inputs on neural dynamics. In the case of the HPG axis, these dynamics are especially complex, because they involve developmental processes that occur even in adult organisms and combine the glandular function of the gonads with their gametogenic function.

Neuroendocrinology is thus a scientific field at the interface between Neuroscience, Endocrinology and Physiology (and even of Developmental Biology in the case of the HPG axis). On a neuroscience ground, mathematical neuroendocrinology is specifically interested in endocrine neurons, which have the uncommon ability of secreting neurohormones into the blood stream. Neuroendocrine networks are characterized by the emergence of very slow rhythms (on the order of an hour), finite size effects due to their relative small number of neurons (on the order of a few thousands for the Gonadotropin-Releasing-Hormone network) and neuroanatomical particularities, that impact the way they can synchronize and desynchronize. On a physiological ground, gonadal cell biology raises specific cell biology issues on more than one account. First, the gonads are the only organs sheltering the germ cell lines (corresponding to oogenesis in ovaries and spermatogenesis in testes). Hence, the two modes of cell division, mitosis and meiosis are encountered in these tissues. Second, there are intricate interactions between the gonadal somatic cells (granulosa cells in the ovaries, sertoli cells in the testes) and the germ cells. Third, the control of gonadal cell populations is exerted within endocrine feedback loops involving both the hypothalamus and pituitary, which results naturally in multiscale population dynamics coupled with hormonally-controlled cell kinetics.

MYCENAE's research topics in mathematical neuroscience deal with complex oscillations, synchronization and plasticity. We study (i) the emergence of network-level behaviors from individual dynamics of excitable cells (mainly neurons, but not exclusively, as the pituitary cells belong to the family of excitable cells): complete synchronization or synchronization of specific events, effect of the recruitment rate in the synchronization process, dependence on the neuro-anatomical and functional coupling properties; (ii) the control of the different possible configurations of the network depending on external (e.g. daylength) and/or internal inputs (e.g. metabolic status), at the source of plasticity processes in cognitive (vision learning) or neuroendocrine systems (differential sensitivity to gonadal steroids and peptides across the different steps of the reproductive life); (iii) the encoding of neuro-hormonal signals as complex oscillations, on the electrical, ionic (calcium dynamics) and secretory levels; and (iv) the decoding of these signals by their target neuronal or non-neuronal cells.

The biological relevance of our modeling and model-based signal analysis approaches is grounded on our network of collaborations with teams of experimentalist biologists. In particular, we have long standing collaborations with the UMR 6175 (INRA-CNRS-Université François Rabelais-Haras Nationaux) “Physiologie de la Reproduction et des Comportements” that covers most our research topics in reproductive neuroendocrinology. We have especially closed links with the Bingo (Integrative Biology of the ovary) and Bios (Biology and Bioinformatics of Signaling Systems) teams, which were partners of the REGATE LSIA. We have been jointly investigating issues relative to terminal or basal follicular development [5] , [6] , analysis of neurosecretory patterns [13] and modeling of GPCR (G-Protein Coupled Receptors) signaling networks [8] . We also have special links with the Center for Interdisciplinary Research in Biology (CIRB, Collège de France), headed by Alain Prochiantz, that help us get a better understanding of how the brain connectivity develops and how it is functionally organized. An instance of a recent collaborative work is the study of the organization of spatial frequencies in the primary visual cortex [42] .