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Vasopressin excites interneurons to suppress hippocampal network activity across a broad span of brain maturity at birth

  1. Kai Kailaa,b,2
  1. aDepartment of Biosciences, University of Helsinki, 00014 Helsinki, Finland;
  2. bNeuroscience Center, University of Helsinki, 00014 Helsinki, Finland;
  3. cCNC Program, Stanford University, Stanford, CA 94305;
  4. dDepartment of Bioengineering, Stanford University, Stanford, CA 94305;
  5. eDepartment of Bioengineering, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305;
  6. fDepartment of Psychiatry, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305
  1. Contributed by Karl Deisseroth, November 2, 2017 (sent for review October 6, 2017; reviewed by Colin Brown and Enrico Cherubini)


The transition from placental to lung-based oxygen supply at mammalian birth involves an obligatory period of asphyxia, which is further aggravated by complications during delivery. This oxygen deprivation is a major threat to the fetal brain, and, under such conditions, hormonal and cardiovascular mechanisms are activated to enhance brain perfusion. Our work now demonstrates an intrinsic mechanism in the fetal brain whereby vasopressin activates hippocampal interneurons, leading to desynchronization and suppression of neuronal network activity in species (rat and guinea pig) that are born at widely different stages of brain maturation. Silencing of synchronous neuronal activity by vasopressin is expected to decrease neuronal energy demand and prevent maladaptive synaptic plasticity, thus acting as a pan-mammalian neuroprotective mechanism during birth.


During birth in mammals, a pronounced surge of fetal peripheral stress hormones takes place to promote survival in the transition to the extrauterine environment. However, it is not known whether the hormonal signaling involves central pathways with direct protective effects on the perinatal brain. Here, we show that arginine vasopressin specifically activates interneurons to suppress spontaneous network events in the perinatal hippocampus. Experiments done on the altricial rat and precocial guinea pig neonate demonstrated that the effect of vasopressin is not dependent on the level of maturation (depolarizing vs. hyperpolarizing) of postsynaptic GABAA receptor actions. Thus, the fetal mammalian brain is equipped with an evolutionarily conserved mechanism well-suited to suppress energetically expensive correlated network events under conditions of reduced oxygen supply at birth.


  • ?1A.S. and P.S. contributed equally to this work.

  • ?2To whom correspondence may be addressed. Email: deissero{at}stanford.edu or kai.kaila{at}helsinki.fi.
  • Author contributions: A.S., P.S., J.V., K.D., and K.K. designed research; A.S., P.S., I.S., M.A.V., J.L., P.U., M.S., A.K.C., B.H., M.P., and E.R. performed research; A.K.C. and K.D. contributed new reagents/analytic tools; A.S., P.S., I.S., M.A.V., J.L., P.U., A.K.C., B.H., M.P., and E.R. analyzed data; and A.S., P.S., M.P., E.R., K.D., and K.K. wrote the paper.

  • Reviewers: C.B., University of Otago; and E.C., SISSA, Trieste, Italy.

  • The authors declare no conflict of interest.

  • This article contains supporting information online at www.danielhellerman.com/lookup/suppl/doi:10.1073/pnas.1717337114/-/DCSupplemental.

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