Postweaning development influences endogenous VPAC1 modulation of LTP induced by theta-burst stimulation: a link to maturation of the hippocampal GABAergic system?

Abstract

Long-term potentiation (LTP) induced by theta-burst stimulation (TBS) undergoes postweaning developmental changes partially linked to GABAergic circuit maturation. Endogenous VIP acting on VPAC1 receptors strongly influences LTP induced by theta-burst stimulation (TBS), an effect dependent on GABAergic transmission. Although VPAC1 receptor levels are developmentally regulated during embryogenesis, its variation along postweaning development is unknow, as is VPAC1 modulation of LTP or its relation to hippocampal GABAergic circuit maturation. As such, we investigated how VPAC1 modulation of LTP adjusts from weaning to adulthood along with GABAergic circuit maturation. As described, LTP induced by TBS (5x4) (5 bursts, 4 pulses delivered at 100Hz) was increasingly greater from weaning to adulthood. The influence of the VPAC1 receptor antagonist PG 97-269 (100nM) on TBS-induced LTP was much larger in juvenile (3-week-old) than in young-adult (6-7-week-old) or adult (12-week-old) rats. This effect was not associated to a developmental decrease in synaptic VPAC1 receptor levels. However, an increase in pre and post synaptic GABAergic synaptic markers, suggests an increase in the number of GABAergic synaptic contacts that is more prominent than the one observed in glutamatergic connections during this period. Conversely, endogenous VPAC2 receptor activation did not significantly influence of TBS-induced LTP. VPAC2 receptor levels enhance pronouncedly during postweaning development, but not at synaptic sites. Given the involvement of VIP interneurons in several aspects of hippocampal-dependent learning, neurodevelopmental disorders, and epilepsy, this could provide important insights into the role of VIP modulation of hippocampal synaptic plasticity during normal and altered brain development potentially contributing to epileptogenesis.