Presynaptic maturation of inhibitory connections onto vasoactive intestinal polypeptide-expressing GABAergic...

Vasoactive intestinal polypeptide-expressing inhibitory interneurons (VIP-INs) in the adult barrel cortex are crucial for mediating active whisking (AW) by disinhibiting pyramidal neurons. Past studies have investigated the development of VIP-IN network integration, focusing mainly on the excitatory network or the postsynaptic side of the inhibitory network. Hence, we aimed to explore the inhibitory network integration of VIP-INs, concentrating on the presynaptic side. We addressed this by investigating VIP-INs in three different age groups (postnatal day (P)8-P10, P14-P16, and P30-P36) in Vip-IRES-cre x tdTomato mice with whole-cell patch clamp recordings. By placing a stimulation electrode into L4 of the barrel field, we elicited electrically-evoked inhibitory postsynaptic currents (eIPSCs) in L2/3 VIP-INs following a high-frequency stimulation. We then analysed recorded eIPSCs by applying the binomial model of synaptic transmission. Our results show significant increases in both the number of readily-releasable vesicles and the presynaptic release probability between P9 and P15, suggesting that the inhibitory network integration is at least partially conducted via a presynaptic functional maturation. Despite an increase in the release probability, synaptic depression is decreased at P30-P36 due to an accelerated vesicle replenishment rate within the same time window. Lastly, asynchronous vesicle release decreases in favour of a stimulus-locked signal transmission by P30-P36. Our results suggest a maturation of the inhibitory projections towards a strong, precise, and stimulus-locked inhibition. This can be physiologically relevant to define the temporal precision of AW at the relevant frequencies.