Systems Neuroscience Section, Department of Neuroscience, Primate Research Institute, and Center for the Evolutionary Origins of Human Behavior, Kyoto University, Inuyama, Aichi, 484-8506, Japan.
Department of Functional Brain Imaging, National Institutes for Quantum Science and Technology, Chiba, 263-8555, Japan.
Nat Commun. 2023 Aug 8;14(1):4762. doi: 10.1038/s41467-023-40436-1.
Recent emphasis has been placed on gene transduction mediated through recombinant adeno-associated virus (AAV) vector to manipulate activity of neurons and their circuitry in the primate brain. In the present study, we created a novel vector of which capsid was composed of capsid proteins derived from both of the AAV serotypes 1 and 2 (AAV1 and AAV2). Following the injection into the frontal cortex of macaque monkeys, this mosaic vector, termed AAV2.1 vector, was found to exhibit the excellence in transgene expression (for AAV1 vector) and neuron specificity (for AAV2 vector) simultaneously. To explore its applicability to chemogenetic manipulation and in vivo calcium imaging, the AAV2.1 vector expressing excitatory DREADDs or GCaMP was injected into the striatum or the visual cortex of macaque monkeys, respectively. Our results have defined that such vectors secure intense and stable expression of the target proteins and yield conspicuous modulation and imaging of neuronal activity.
最近的研究重点放在通过重组腺相关病毒（AAV）载体介导的基因转导上，以操纵灵长类动物大脑中神经元及其回路的活性。在本研究中，我们构建了一种新型载体，其衣壳由来自 AAV 血清型 1 和 2（AAV1 和 AAV2）的衣壳蛋白组成。该 mosaic 载体（命名为 AAV2.1 载体）在猕猴额叶皮层注射后，同时表现出优异的转基因表达（针对 AAV1 载体）和神经元特异性（针对 AAV2 载体）。为了探索其在化学遗传学操作和活体钙成像中的适用性，分别将表达兴奋性 DREADDs 或 GCaMP 的 AAV2.1 载体注射到猕猴的纹状体或视皮层中。我们的结果表明，这些载体可以确保靶蛋白的强烈和稳定表达，并产生明显的神经元活动调节和成像。
