# Toxoplasma gondii-induced region-specific disintegration in glutamatergic neurotransmission is linked to cognitive impairments in mice

## TL;DR

This study shows that chronic infection with Toxoplasma gondii disrupts brain communication in mice, leading to cognitive and motor issues that are only partially reversed by treatment.

## Contribution

The paper causally links T. gondii infection to region-specific glutamatergic impairments and treatment-resistant behavioral traits in mice.

## Key findings

- T. gondii infection disrupts glutamatergic signaling in the hippocampus, striatum, and cortex.
- Sulfadiazine treatment only partially restores behavioral and synaptic impairments.
- Infection impairs motor actions, social interaction, and the balance between goal-directed and habitual behaviors.

## Abstract

Chronic infection with the protozoan parasite Toxoplasma gondii (T. gondii) elicits distinct alterations in both the immune and nervous system of the host. Previous studies correlated the persistent neuroinflammatory response triggered by chronic T. gondii infection to specific behavioral alterations. Here, we causally link chronic cerebral T. gondii infection to cognitive and motor impairments in mice, as well as to the altered brain glutamatergic signaling in hippocampus, striatum, and cortex. By combining synaptic composition analysis assessed via flow synaptometry with the standard sulfadiazine treatment, we demonstrated the regional specificity of the detected alterations of cerebral T. gondii infection. Importantly, our behavioral analysis exposed the restoration of behavioral flexibility in shifting between goal-directed and habitual action control, with more motorically demanding skills such as social novelty recognition and locomotion being only partially restored. We argue that the revealed regional effects of both T. gondii and sulfadiazine treatment may be a key factor accounting for treatment-resistant behavioral traits.

•T. gondii causes neuroinflammation and hampers Glu synaptic neurotransmission•Synapses are impaired at structural and functional levels with a regional tropism•T. gondii hinders motor actions, social interaction, goal-directed/habitual balance•Sulfadiazine causes only a partial restoration of neurotransmission and behavior

T. gondii causes neuroinflammation and hampers Glu synaptic neurotransmission

Synapses are impaired at structural and functional levels with a regional tropism

T. gondii hinders motor actions, social interaction, goal-directed/habitual balance

Sulfadiazine causes only a partial restoration of neurotransmission and behavior

Immunology; Parasitology; Neuroscience; Cognitive neuroscience