Simacek Clara A, Kirischuk Sergei, Mittmann Thomas
Institute for Physiology, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany.
Acta Physiol (Oxf). 2025 Feb;241(2):e14265. doi: 10.1111/apha.14265.
Despite dysfunctional vasoactive intestinal polypeptide-positive interneurons (VIP-INs) being linked to the emergence of neurodevelopmental disorders, the temporal profile of VIP-IN functional maturation and cortical network integration remains unclear.
Postnatal VIP-IN development was traced with patch clamp experiments in the somatosensory cortex of Vip-IRES-cre x tdTomato mice. Age groups were chosen during barrel field formation, before and after activation of main sensory inputs, and in adult animals (postnatal days (P) P3-4, P8-10, P14-16, and P30-36).
Changes in passive and active membrane properties show a maturation towards accelerated signal integrations. Excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) showed progressive VIP-IN integration into cortical networks, likely via synaptogenesis: mEPSC frequency increased before P8-10, while mIPSC frequency increased at P14-16. Only mIPSC kinetics became accelerated, and the E/I ratio of synaptic inputs, defined as a ratio of mEPSC to mIPSC charge transfer, remained constant throughout the investigated developmental stages. Evoked (e)EPSCs and (e)IPSCs showed increased amplitudes, while only eIPSCs demonstrated faster kinetics. eEPSCs and eIPSCs revealed a paired-pulse facilitation by P14-16, indicating probably a decrease in the presynaptic release probability (p) and a paired-pulse depression in adulthood. eIPSCs also showed the latter, suggesting a decrease in p for both signal transmission pathways at this time point.
VIP-INs mature towards faster signal integration and pursue different strategies to avoid overexcitation. Excitatory and inhibitory synaptic transmission become stronger and shorter via different pre- and postsynaptic alterations, likely promoting the execution of active whisking.
尽管血管活性肠肽阳性中间神经元(VIP-INs)功能失调与神经发育障碍的出现有关,但VIP-IN功能成熟和皮质网络整合的时间概况仍不清楚。
采用膜片钳实验追踪出生后Vip-IRES-cre x tdTomato小鼠体感皮层中VIP-IN的发育情况。在桶状区形成期间、主要感觉输入激活之前和之后以及成年动物(出生后第(P)3 - 4天、P8 - 10天、P14 - 16天和P30 - 36天)选择年龄组。
被动和主动膜特性的变化表明向加速信号整合的方向成熟。兴奋性和抑制性突触后电流(EPSCs和IPSCs)显示VIP-IN逐渐整合到皮质网络中,可能是通过突触发生:微小兴奋性突触后电流(mEPSC)频率在P8 - 10天之前增加,而微小抑制性突触后电流(mIPSC)频率在P14 - 16天增加。只有mIPSC动力学加快,并且突触输入的兴奋/抑制(E/I)比(定义为mEPSC与mIPSC电荷转移之比)在整个研究的发育阶段保持恒定。诱发的(e)EPSCs和(e)IPSCs振幅增加,而只有eIPSCs显示出更快的动力学。到P14 - 16天,eEPSCs和eIPSCs显示出双脉冲易化,这可能表明突触前释放概率(p)降低,而在成年期出现双脉冲抑制。eIPSCs此时也显示出后者,表明在这个时间点两种信号传递途径的p都降低。
VIP-INs朝着更快的信号整合方向成熟,并采取不同策略避免过度兴奋。兴奋性和抑制性突触传递通过不同的突触前和突触后改变变得更强且更短,这可能促进了主动触须运动的执行。