Identification and functional characterization of an oxytocin neuronal population coordinating lactation

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The hypothalamic neuropeptide oxytocin (OT) is an essential molecule for initiation and maintenance of lactation - a unique functional state of offspring nourishing typical for mammals. The central OT system is composed of two distinct cell types - magnocellular and parvocellular OT neurons. Magnocellular OT neurons are the main cellular components of the system due to their unique synchronous bursting activity, eliciting release of OT into blood circulatory system to induce milk let-down from the mammary glands. The basic mechanisms underlying this synchronicity are still, however, largely unknown. Our recent finding in virgin rats demonstrated that the other cellular components of the OT system, the parvocellular OT neurons, can directly control both OT magnocellular neuron activity and systemic OT release in response to sensory stimulation. Following this finding and also based on unpublished preliminary results included in the present proposal, we here aim to demonstrate that the parvocellular OT neurons also contribute to the regulation of magnocellular neuron activity during lactation. In the course of our prospective study we will use complementary expertise of our laboratories in Germany and Switzerland, using newly developed viral vectors for opto- and pharmacogenetic approaches to study the importance of parvocellular OT neurons using in vivo multi-unit opto-electrode recordings in combination with the monitoring of suckling behaviour in lactating rats. These techniques will first be implemented to perform loss-of-function chemo,- and optogenetic experiments to prove the causal relation between the activity of parvocellular OT neurons and changes in weight gain of suckling pups and bursting of magnocellular OT neurons during lactation. Next, in a gain-of-function setup we will rescue changed in breast feeding and magnocellular OT neuron firing activity that are induced by nipple sensory deprivation, via optogenetic activation of parvocellular OT neurons. Finally, applying a cocktail of monosynaptic retrogradely transmitted viruses we will reconstruct the neural pathways between mammary glands and parvocellular OT neurons and with the above described approaches, examine their functional importance for inducing lactation. Collectively, our work will dissect novel OT network initiating and/or maintaining lactation, which will be important to further our understanding of the basic mechanisms of reproductive physiology.