McFarlan Amanda R, Gomez Isabella, Chou Christina Y C, Alcolado Adam, Costa Rui Ponte, Sjöström P Jesper
Centre for Research in Neuroscience, Brain Repair, and Integrative Neuroscience Program, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC, Canada.
Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada.
Front Synaptic Neurosci. 2024 Aug 29;16:1433977. doi: 10.3389/fnsyn.2024.1433977. eCollection 2024.
Short-term plasticity is an important feature in the brain for shaping neural dynamics and for information processing. Short-term plasticity is known to depend on many factors including brain region, cortical layer, and cell type. Here we focus on vasoactive-intestinal peptide (VIP) interneurons (INs). VIP INs play a key disinhibitory role in cortical circuits by inhibiting other IN types, including Martinotti cells (MCs) and basket cells (BCs). Despite this prominent role, short-term plasticity at synapses to and from VIP INs is not well described. In this study, we therefore characterized the short-term plasticity at inputs and outputs of genetically targeted VIP INs in mouse motor cortex. To explore inhibitory to inhibitory (I → I) short-term plasticity at layer 2/3 (L2/3) VIP IN outputs onto L5 MCs and BCs, we relied on a combination of whole-cell recording, 2-photon microscopy, and optogenetics, which revealed that VIP IN→MC/BC synapses were consistently short-term depressing. To explore excitatory (E) → I short-term plasticity at inputs to VIP INs, we used extracellular stimulation. Surprisingly, unlike VIP IN outputs, E → VIP IN synapses exhibited heterogeneous short-term dynamics, which we attributed to the target VIP IN cell rather than the input. Computational modeling furthermore linked the diversity in short-term dynamics at VIP IN inputs to a wide variability in probability of release. Taken together, our findings highlight how short-term plasticity at VIP IN inputs and outputs is specific to synapse type. We propose that the broad diversity in short-term plasticity of VIP IN inputs forms a basis to code for a broad range of contrasting signal dynamics.
短期可塑性是大脑中塑造神经动力学和信息处理的一个重要特征。已知短期可塑性取决于许多因素，包括脑区、皮层层和细胞类型。在这里，我们聚焦于血管活性肠肽（VIP）中间神经元（INs）。VIP中间神经元在皮层回路中通过抑制其他类型的中间神经元，包括马丁诺蒂细胞（MCs）和篮状细胞（BCs），发挥关键的去抑制作用。尽管有这一突出作用，但与VIP中间神经元之间突触的短期可塑性尚未得到充分描述。因此，在本研究中，我们对小鼠运动皮层中基因靶向的VIP中间神经元的输入和输出处的短期可塑性进行了表征。为了探究在第2/3层（L2/3）VIP中间神经元输出到第5层MCs和BCs上的抑制性到抑制性（I→I）短期可塑性，我们结合了全细胞记录、双光子显微镜和光遗传学，结果显示VIP中间神经元→MC/BC突触始终是短期抑制的。为了探究VIP中间神经元输入处的兴奋性（E）→I短期可塑性，我们使用了细胞外刺激。令人惊讶的是，与VIP中间神经元的输出不同，E→VIP中间神经元突触表现出异质性的短期动力学，我们将其归因于目标VIP中间神经元细胞而非输入。计算建模进一步将VIP中间神经元输入处短期动力学的多样性与释放概率的广泛变化联系起来。综上所述，我们的发现突出了VIP中间神经元输入和输出处的短期可塑性如何因突触类型而异。我们提出，VIP中间神经元输入处短期可塑性的广泛多样性构成了编码广泛对比信号动力学的基础。
