Injection with Toxoplasma gondii protein affects neuron health and survival

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.