Oxytocin is an evolutionarily conserved neuromodulator that is implicated in social and maternal behaviors in animals, as well as autism spectrum disorders and schizophrenia in humans. We identified robust expression of oxytocin receptors and oxytocinergic axons in hippocampal area CA2, a distinct region that is critical for social memory and implicated in neurological disorders. In many cases oxytocin exclusively modulates inhibitory cell function, however here we reveal a very different scenario; oxytocin receptor activation dependably excites pyramidal cells in CA2, as well as neighboring fast-spiking, parvalbumin-positive interneurons. We find that oxytocin depolarizes CA2 pyramidal cells and increases total membrane resistance. Additionally, spike configuration is altered to facilitate repetitive spiking and high frequency burst activity. These bursts are sculpted by a concerted set of mechanisms downstream of G-protein coupled receptor activation that lead to modification of both voltage gated potassium and sodium conductances. We show that the resulting high frequency, periodic burst patterns are important for tuning CA2 output onto neighboring CA1 pyramidal cells, the primary target of CA2 axons. Oxytocin shapes the intensity and duration of CA2 spike bursts by modulation of both intrinsic cell properties and local inhibition. This significantly impacts synaptic short-term plasticity and efficacy of information transfer of CA2 output onto CA1.
|Advisor:||Tsien, Richard W.|
|Commitee:||Fishell, Gordon, Froemke, Robert C., Lin, Dayu, Siegelbaum, Steven A.|
|School:||New York University|
|Department:||Basic Medical Science|
|School Location:||United States -- New York|
|Source:||DAI-B 78/08(E), Dissertation Abstracts International|
|Keywords:||Burst firing, CA2 neurons, G-protein coupled receptor, Hippocampus, Oxytocin, Pyramidal cells|
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