Simacek Clara A, Kirischuk Sergei, Mittmann Thomas
Institute for Physiology, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany.
Pflugers Arch. 2025 Jun 25. doi: 10.1007/s00424-025-03101-8.
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.
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。