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

Abstract

SignificanceThe 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.

Oxytocin and vasopressin in the rodent hippocampus

“…Sparse Avpr1a‐EGFP‐positive cells are seen in DG hilar region as well as the stratum oriens, stratum pyramidale and stratum radiatum of CA3, CA2 and CA1 regions, suggesting Avpr1a is present on GABAergic interneurons . Accordingly, ISH in the CA3 region of neonatal rats show colocalization of Avpr1a but not Avpr1b with a Gad1/2 . More detailed descriptions of Avpr1a in specific hippocampal interneuron subpopulations are lacking.…”

“…In fact, pharmacological activation of GABA A receptors during the perinatal period indicate that GABA remains depolarizing throughout this period. Rather, Avp‐induced suppression of hippocampal activity involves a reduction in synchronous discharges in the CA3 region via disruption of rhythmic interneuron activity . Thus, both Oxt and Avp play a critical role in regulating hippocampal activity during birth; however, the underlying mechanisms merit further investigation.…”

“…Moreover, recordings from CA3 principal neurons show that activation of the Oxtr induces a significant membrane depolarization, which may result in enhanced CA3 excitatory output onto other hippocampal regions. Studies examining Avp‐induced changes of CA3 activity in adult rodents are lacking; however, application of Avp does indirectly reduce giant depolarizing potentials of CA3 principal neurons in slices prepared from perinatal rats …”

“…With respect to Avp, only GABAergic transmission in the CA3 region of the perinatal rat brain has been studied. At this stage of development, Avp enhances GABA release onto pyramidal cells via enhancing excitability of Avpr1a‐expressing interneurons of the stratum lacunosum moleculare and stratum radiatum …”

“…Perinatal Avp signaling may also be neuroprotective. Avp excites the perinatal hippocampal interneurons via Avpr1a leading to suppression of network activity, which may reduce energetic demand during hypoxic conditions associated with parturition . Whereas Oxt signaling induces a transient GABA shift from excitatory to inhibitory action, this mechanism is not involved in Avp‐induced suppression of hippocampal activity.…”