Functional specialization within the central oxytocin system(s) (#33)
Oxytocin (OT), the neuropeptide of sociality, is expressed in parvo- and magnocellular neurons localized in the hypothalamic paraventricular, supraoptic, and accessory nuclei. The plethora of OT effects in distinct brain regions suggests functional and anatomical segregation within the central OT system. Using viral-based and conventional retrograde tracing we showed that magnocellular OT neurons, which innervate different forebrain regions are (in most cases) situated distinct from each other. To further prove the functional segregation within OT system, we developed and applied new genetic technique named “virus-mediated genetic activity-induced tagging” (vGAIT). The use of vGAIT in behaving animals allowed us to genetically tag OT neurons, which were active upon a certain behavioral demand, such as fear response. Combining vGAIT with optogenetics, we found that the associative fear learning activates 15% of OT neurons. Importantly, these neurons (even in small number) are sufficient to drastically attenuate fear response via axonal OT release in the central amygdala. In respect to the parvocellular OT system, it is very likely that these neurons are also differing in their projections and functions. We identified a group of parvocellular OT cells that synapse onto magnocellular OT neurons and simultaneously projects to the spinal cord. Our preliminary results suggest the contribution of this novel “parvo-magno” OT circuit in the regulation of pain perception. In conclusion, our data provide arguments for the specialization within the OT system. Furthermore, we speculate about possible existence of functional OT modules, which have specific input and output, are activated by specific stimuli, and modulate distinct behaviors.