Reproduction is an essential feature of living organisms and is largely modulated in vertebrates by hypothalamic neuropeptide oxytocin (OT) and its homologs. In mammals, reproductive function is realized by complex socio-sexual (SS) behaviors, which can be modulated by OT. However, precise OT circuits underlying OT effects are far from clear.
Our previous study (Eliava et al., Neuron, 2016) revealed a small fraction of OT neurons (so called “parvocellular” OT neurons), which drives activity of entire population of magnocellular neurons. The efficiency of ~ 100 parvocellular OT neurons to activate ~ 10.000 magnocellular neurons has been demonstrated by us under condition of acute inflammatory pain. Following this discovery we decided to expand this study asking whether the same OT parvocellular neurons can coordinate activity of the central OT system via non-nociceptive stimuli (such as social touch) to promote socio-sexual behaviour.
The present ANR-DFG project was the occasion to bring new technologies to our lab, namely freely moving in vivo calcium imaging, which was used to compliment in vivo electrophysiology recordings. Thus, in order to better tackle the oxytocin-regulated socio-sexual behaviour, we decided to spent significant amount of time to bring these technologies in our lab. The main difficulty relies on the depth of the recorded structures: near 1 cm for both the rats PVN and the SON.
In the course of our study, we obtained the following major results:
4. Oxytocin neurons are activated during social interactions between female rats, principally by direct physical touch.
5. A specific small subpopulation of oxytocin neurons, (parvocellular neurons of the PVN), are preferentially activated by tactile stimulation and these transmit activation to the much larger population of magnocellular oxytocin neurons.
6. Chemogenetic-based selective activation of these parvocellular oxytocin neurons in female rats promoted social interaction with an unfamiliar female. Conversely, the selective inhibition of these neurons suppressed social interactions.
All the results obtained in the course of the project have or will be published in peer reviewed journals.
5 commons articles have been published around this project by the project coordinators
Reproduction is an essential feature of living organisms and is largely modulated in vertebrates by hypothalamic neuropeptide oxytocin (OT) and its homologs. In mammals, reproductive function is realized by complex socio-sexual (SS) behaviors, which can be mechanistically divided into precopulatory and copulatory behaviors, both modulated by OT. However, precise OT circuits underlying OT effects are far from clear. Although there are no doubts that OT promotes sexual behavior, the OT circuits orchestrating precopulatory behavior via forebrain regions are largely unknown. To address these questions, we will employ a recently developed genetic technique (called “virus-based Genetic Activity-Induced Tagging” and abbreviated as vGAIT) to tag only those OT neurons which were activated during precopulatory and copulatory behaviors of rats. Using this technique, we will elucidate spatial distribution of such OT neurons in the hypothalamus, their phenotype and their projections as well as identify structures receiving input from tagged OT neurons in the forebrain, brainstem, and spinal cord. In parallel, in freely moving rats, we will record the activity of these OT neurons to elucidate their properties and excitability during SS behavior. Based on anatomical data, we will stimulate axonal OT release in those forebrain structures which are functionally related with SS behavior. At the end, using optogenetic and pharmacogenetic techniques, we will activate or inhibit entire populations of tagged OT neurons to monitor changes in SS behavior. The expected data will be entirely novel and will provide mechanistic insights into the physiology of the OT system in the context of SS behavior. Our proposal is highly relevant to human health as it will provide a basis for pathogenesis and possible pharmacological intervention in patients experiencing problems with sexual arousal and reproductive function.
Monsieur Alexandre Charlet (CNRS - UPR3212)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
INCI CNRS - UPR3212
DKFZ Schaller Research Group on Neuropeptides, German Cancer Research Center, CellNetwork Cluster of Excellence
Help of the ANR 208,000 euros
Beginning and duration of the scientific project: January 2017 - 36 Months