抑制性中间神经元(INs)的可塑性在皮质微电路的组织和维持中起着重要作用。鉴于许多不同的IN类型,在兴奋性到兴奋性(E→I)时,突触类型特定的可塑性学习规则具有更大的多样性,I→E,我→我突触。I→I突触在皮质回路中起着关键的去抑制作用。因为它们通常以其他INs为目标,血管活性肠肽(VIP)INs通常表现为I→I→E去抑制,上调附近兴奋性神经元的活动。因此,VIPIN失调可导致神经病理学如癫痫。尽管VIPINs具有重要的活动调节作用,它们的长期可塑性尚未被描述。因此,我们在遗传定义的VIPIN的输入和输出处表征了尖峰时间依赖性可塑性(STDP)的现象学。使用全细胞记录的组合,双光子显微镜,光遗传学,我们在第2/3层(L2/3)VIPIN输出上探索了I→ISTDP到L5Martinotti细胞(MC)和篮状细胞(BC)。我们发现VIPIN→MC突触经历了突触前表达的因果长期抑郁(LTD)。VIPIN→BC连接,然而,没有经历任何可检测的可塑性。相反,利用细胞外刺激,我们探索了输入VIPINs时的E→ISTDP,这些输入揭示了因果和绝经期的长期增强(LTP)。一起来看,我们的结果表明VIPIN在其输入和输出处具有突触类型特定的学习规则.这表明在长期可塑性中利用VIP来控制活动相关的神经病理学如癫痫的可能性。
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.