Toxoplasma gondii 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 Toxoplasma-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 Toxoplasma protein— either directly or indirectly— affects neuronal health and survival. Collectively, these data offer the first insights into which neurons interact with Toxoplasma and how these interactions alter neuron physiology in vivo.
Data for Figures 1,2,3,5,6,7 is provided.
- Oscar A Mendez
- Emiliano Flores Machado
- Anita Koshy
- Anita Koshy
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All mouse studies and breeding were carried out in accordance with the Public Health Service Policy on Human Care and Use of Laboratory Animals. The protocol was approved by the University of Arizona Institutional Animal Care and Use Committee. (#A-3248-01, protocol #12-391).
- Malcolm J McConville, The University of Melbourne, Australia
- Received: February 18, 2021
- Accepted: June 9, 2021
- Accepted Manuscript published: June 9, 2021 (version 1)
© 2021, Mendez et al.
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