# Presynaptic maturation of inhibitory connections onto vasoactive intestinal polypeptide-expressing GABAergic interneurons in the mouse barrel field

## TL;DR

The study shows how inhibitory connections onto VIP-expressing neurons mature presynaptically in the mouse barrel cortex during development.

## Contribution

The paper reveals presynaptic maturation of inhibitory connections onto VIP-INs, focusing on functional changes in vesicle release and transmission precision.

## Key findings

- Presynaptic release probability and vesicle numbers increase significantly between P9 and P15.
- Synaptic depression decreases at P30–P36 due to faster vesicle replenishment.
- Asynchronous vesicle release decreases, favoring stimulus-locked transmission by P30–P36.

## Abstract

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.

The online version contains supplementary material available at 10.1007/s00424-025-03101-8.