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小鼠桶状皮质中,向表达血管活性肠肽的γ-氨基丁酸能中间神经元的抑制性连接的突触前成熟。

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

作者信息

Simacek Clara A, Kirischuk Sergei, Mittmann Thomas

机构信息

Institute for Physiology, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany.

出版信息

Pflugers Arch. 2025 Jun 25. doi: 10.1007/s00424-025-03101-8.

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.

摘要

成年桶状皮质中表达血管活性肠肽的抑制性中间神经元(VIP-INs)对于通过解除锥体神经元的抑制来介导主动触须运动(AW)至关重要。过去的研究调查了VIP-IN网络整合的发育情况,主要集中在兴奋性网络或抑制性网络的突触后方面。因此,我们旨在探索VIP-INs的抑制性网络整合,重点关注突触前方面。我们通过在Vip-IRES-cre x tdTomato小鼠的三个不同年龄组(出生后第(P)8 - P10、P14 - P16和P30 - P36)中使用全细胞膜片钳记录来研究VIP-INs,从而解决了这个问题。通过将刺激电极置于桶状区域的L4,我们在高频刺激后在L2/3 VIP-INs中诱发电诱发抑制性突触后电流(eIPSCs)。然后,我们应用突触传递的二项式模型分析记录的eIPSCs。我们的结果表明,在P9和P15之间,易于释放的囊泡数量和突触前释放概率均显著增加,这表明抑制性网络整合至少部分是通过突触前功能成熟来进行的。尽管释放概率增加,但由于在同一时间窗口内囊泡补充速率加快,在P30 - P36时突触抑制减弱。最后,到P30 - P36时,异步囊泡释放减少,有利于刺激锁定信号传递。我们的结果表明,抑制性投射成熟为一种强大、精确且刺激锁定的抑制。这在生理上可能与在相关频率下定义AW的时间精度有关。

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