Fast and (sometimes) furious: Oxytocinergic modulation of fast-spiking interneurons in hippocampal CA1 region and caudoputamen of mice

Sociability is an extremely complex behavior that requires the involvement and coordination of different brain areas. The hypothalamic neuropeptide oxytocin (OT) plays a pivotal role in regulating various aspects of social behavior and can reach and modulate many regions of the central nervous system. However, the mechanisms through which it modulates neuronal activity are still unclear, also because this peptide can exert different effects depending on the brain area and on the neuronal type. In this work, we investigated and deepened the action of OT on a specific subpopulation of interneurons, the fast-spiking interneurons (FS-INs), which are widely distributed in the brain. Here, we specifically focused on the FS-INs residing in two regions involved with social behavior, the hippocampus and the caudoputamen. We observed that in the CA1 area of the hippocampus, TGOT, an OT analogous, depolarizes the cells, increases their firing rate and excitability, and modifies their action potential shape. Moreover, linear mixed-effects models demonstrated that all the TGOT-induced effects on CA1 FS-INs are independent of each other. On the other hand, in the caudoputamen the prevalent effect of TGOT was an inhibition of the FS-INs. Altogether, these results reveal new ways in which OT can finely modulate neuronal activity and demonstrate how oxytocinergic neuromodulation is highly precise, up to acting differently on the same neuronal subpopulation in a region-specific manner.