Shaping neocortical networks via maturation of synaptic functions in VIP-positive GABAergic interneurons

GABAergic interneurons (INs) highly impact cortical development. For instance, early postnatal dysregulation of vasoactive intestinal polypeptide (VIP)- expressing GABAergic INs has been shown to impair sensory processing and learning, emerging from adolescence on. Thus, investigating the functional maturation and network integration of VIP-INs is important for understanding brain development. Here, we studied developmental changes in passive and active membrane parameters of VIP-INs and their network integration into the developing neocortex with an emphasised focus on the maturation of their inhibitory connections. We performed patch-clamp recordings on VIP-INs in L2/3 of the somatosensory cortex at three postnatal stages (P8 – P10, P14 – P16, P30 – P36) in a vip x tdTomato reporter mouse line.Passive and active membrane properties revealed a functional maturation of most parameters between the 2nd and 3rd postnatal week. Miniature excitatory postsynaptic currents showed an increased frequency while their kinetics remained unchanged, suggesting a maturation mainly via synaptogenesis. Miniature inhibitory postsynaptic currents (mIPSCs) demonstrated increases in frequency and amplitude, additionally to accelerated kinetics. This indicates that inhibitory connections undergo a more complex maturation, including pre- and postsynaptic tunings. We associate the accelerated postsynaptic mIPSC kinetics with a switch in GABAA receptor subunits. Quantitative analysis of evoked IPSCs yielded an increased presynaptic readily releasable pool size and number of release sites, accompanied with a reduced release probability, suggesting information transfer at higher frequency without synaptic fatigue. In conclusion, inhibitory connections onto VIP-INs mature towards a precise, time-locked synaptic transmission.Supported by the German Research Foundation (DFG, CRC1080, C02) to T.M.