The plasticity of inhibitory interneurons (INs) plays an important role in the organization and maintenance of cortical microcircuits. Given the many different IN types, there is an even greater diversity in synapse-type-specific plasticity learning rules at excitatory to excitatory (E→I), I→E, and I→I synapses. I→I synapses play a key disinhibitory role in cortical circuits. Because they typically target other INs, vasoactive intestinal peptide (VIP) INs are often featured in I→I→E disinhibition, which upregulates activity in nearby excitatory neurons. VIP IN dysregulation may thus lead to neuropathologies such as epilepsy. In spite of the important activity regulatory role of VIP INs, their long-term plasticity has not been described. Therefore, we characterized the phenomenology of spike-timing-dependent plasticity (STDP) at inputs and outputs of genetically defined VIP INs. Using a combination of whole-cell recording, 2-photon microscopy, and optogenetics, we explored I→I STDP at layer 2/3 (L2/3) VIP IN outputs onto L5 Martinotti cells (MCs) and basket cells (BCs). We found that VIP IN→MC synapses underwent causal long-term depression (LTD) that was presynaptically expressed. VIP IN→BC connections, however, did not undergo any detectable plasticity. Conversely, using extracellular stimulation, we explored E→I STDP at inputs to VIP INs which revealed long-term potentiation (LTP) for both causal and acausal timings. Taken together, our results demonstrate that VIP INs possess synapse-type-specific learning rules at their inputs and outputs. This suggests the possibility of harnessing VIP IN long-term plasticity to control activity-related neuropathologies such as epilepsy.

中文翻译：

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运动皮层 VIP 中间神经元的尖峰时间依赖性可塑性

抑制性中间神经元（IN）的可塑性在皮质微电路的组织和维护中发挥着重要作用。考虑到许多不同的 IN 类型，兴奋性到兴奋性 (E→I)、I→E 和 I→I 突触的突触类型特异性可塑性学习规则存在更大的多样性。 I→I 突触在皮质回路中发挥着关键的去抑制作用。因为它们通常以其他 IN 为目标，所以血管活性肠肽 (VIP) IN 通常以 I→I→E 去抑制为特征，从而上调附近兴奋性神经元的活动。 VIP IN 失调可能会导致神经病理学，例如癫痫。尽管 VIP IN 具有重要的活动调节作用，但其长期可塑性尚未被描述。因此，我们对基因定义的 VIP IN 的输入和输出处的尖峰时间依赖性可塑性 (STDP) 现象进行了表征。结合全细胞记录、2 光子显微镜和光遗传学，我们探索了 L5 Martinotti 细胞 (MC) 和篮子细胞 (BC) 2/3 (L2/3) VIP IN 输出上的 I→I STDP。我们发现 VIP IN→MC 突触经历了突触前表达的因果性长期抑制 (LTD)。然而，VIP IN→BC 连接没有经历任何可检测到的可塑性。相反，使用细胞外刺激，我们探索了 VIP IN 输入处的 E→I STDP，这揭示了因果时间和非因果时间的长期增强（LTP）。总而言之，我们的结果表明 VIP IN 在其输入和输出处具有突触类型特定的学习规则。这表明利用 VIP 的长期可塑性来控制与活动相关的神经病理学（例如癫痫）的可能性。