Graduate Interdisciplinary Program in Neuroscience, University of Arizona, Tucson, United States.
BIO5 Institute, University of Arizona, Tucson, United States.
Elife. 2021 Jun 9;10:e67681. doi: 10.7554/eLife.67681.
is an intracellular parasite that causes a long-term latent infection of neurons. Using a custom MATLAB-based mapping program in combination with a mouse model that allows us to permanently mark neurons injected with parasite proteins, we found that -injected neurons (TINs) are heterogeneously distributed in the brain, primarily localizing to the cortex followed by the striatum. In addition, we determined that cortical TINs are commonly (>50%) excitatory neurons (FoxP2) and that striatal TINs are often (>65%) medium spiny neurons (MSNs) (FoxP2). By performing single neuron patch clamping on striatal TINs and neighboring uninfected MSNs, we discovered that TINs have highly aberrant electrophysiology. As approximately 90% of TINs will die by 8 weeks post-infection, this abnormal physiology suggests that injection with protein-either directly or indirectly-affects neuronal health and survival. Collectively, these data offer the first insights into which neurons interact with and how these interactions alter neuron physiology in vivo.
是一种细胞内寄生虫,可导致神经元的长期潜伏感染。我们使用基于 MATLAB 的定制映射程序和一种可使我们永久标记注入寄生虫蛋白的神经元的小鼠模型,发现-注入神经元(TINs)在大脑中呈异质分布,主要定位于皮层,其次是纹状体。此外,我们确定皮层 TINs 通常 (>50%)为兴奋性神经元(FoxP2),而纹状体 TINs 通常 (>65%)为中型棘突神经元(MSNs)(FoxP2)。通过对纹状体 TINs 和邻近未感染的 MSNs 进行单个神经元膜片钳钳制,我们发现 TINs 的电生理学非常异常。由于大约 90%的 TINs 将在感染后 8 周内死亡,这种异常生理学表明,蛋白的注入——无论是直接还是间接——会影响神经元的健康和存活。总的来说,这些数据首次提供了有关哪些神经元与相互作用以及这些相互作用如何改变体内神经元生理学的见解。