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

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.

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Journal
Pflügers Archiv - European Journal of Physiology
Published
2025-06-24
DOI
https://doi.org/10.1007/s00424-025-03101-8
Primary Topic
Neuroscience and Neuropharmacology Research
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Clara A. Simacek, Thomas Mittmann, Sergei Kirischuk
Pflügers Archiv - European Journal of Physiology
Neuroscience and Neuropharmacology Research
article

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

Clara A. Simacek, Thomas Mittmann, Sergei Kirischuk
article en

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.

Pflügers Archiv - European Journal of PhysiologyVol. 477(8)
Johannes Gutenberg University Mainz (DE), University Medical Center of the Johannes Gutenberg University Mainz (DE)
Deutsche Forschungsgemeinschaft, Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Good health and well-being
Openalex Percentile: Top 84%
Neuroscience and Neuropharmacology Research
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