Oxytocin signals via Gi and Gq to drive persistent CA2 pyramidal cell firing and strengthen CA3-CA1 neurotransmission

The oxytocin receptor (OXTR) is concentrated in specific brain regions, exemplified by hippocampal subregion CA2, that support social information processing. Oxytocinergic modulation of CA2 directly affects social behavior, yet how oxytocin regulates activity in CA2 remains incompletely understood. We found that OXTR stimulation acts via closure of M-current potassium channels in all OXT-sensitive CA2 neurons. M-current inhibition was persistent in CA2 pyramidal cells, whose prolonged burst firing required functional coupling of the OXTR to both Gq and Gi proteins. Other neuromodulators acted via distinct patterns of G-protein signaling to induce CA2 pyramidal neuron burst firing, underscoring its likely importance. CA2 burst firing impacted hippocampal subregion CA1 where stratum oriens-resident CA1 interneurons were targeted more strongly than CA1 pyramidal cells. Oxytocinergic modulation of interneurons, via CA2 pyramidal cell input and directly, triggered a long-lasting enhancement of CA3-CA1 transmission. Thus, transient activation of oxytocinergic inputs may initiate long-lasting recording of social information.