Toxoplasma gondii infection induces dendritic retraction in basolateral amygdala accompanied by reduced corticosterone secretion

Abstract

Pathological anxiety is thought to reflect a maladaptive state characterized by exaggerated fear. Naturally occurring perturbations that reduce fear can be crucial in the search for new treatments. The protozoan parasite Toxoplasma gondii invades rat brain and removes the fear that rats have of cat odors, a change believed to be parasitic manipulation of host behavior aimed at increasing parasite transmission. It is likely that mechanisms employed by T. gondii can be used as a heuristic tool to understand possible means of fear reduction in clinical settings. Male Long-Evans rats were infected with T. gondii and compared with sham-infected animals 8 weeks after infection. The amount of circulating plasma corticosterone and dendritic arborization of basolateral amygdala principal neurons were quantified. Previous studies have shown that corticosterone, acting within the basolateral amygdala, enhances the fear response to environmental stimuli. Here we show that T. gondii infection causes a dendritic retraction in basolateral amygdala neurons. Such dendritic retraction is accompanied by lower amounts of circulating corticosterone, both at baseline and when induced by an aversive cat odor. The concerted effects of parasitism on two pivotal physiological nodes of the fear response provide an animal model relevant to interactions between stress hormones and amygdalar plasticity.

Fig. 1.

Two-way analysis of variance revealed significant effects of infection and hemisphere of sampling. Values of estimated marginal means are depicted as mean ± s.e.m. Ordinate depicts total dendritic length. *P<0.01 compared with left hemisphere; **P<0.000001 compared with control. Please note that ordinate does not start at zero.

Fig. 2.

Planned comparisons revealed that infection reduced total dendritic length in both left and right hemisphere. Dot and whiskers depict mean ± s.e.m. Box plots depict median, 25th percentile and 75th percentile. *P<0.01, **P<0.0001 compared with controls, using Student’s t-test after Bonferroni correction; n= 18 for control neurons in left hemisphere, 36 for infected left, 48 for control right and 24 for infected right. Neurons were derived from four control and four infected animals (12-32 neurons per animal). Please note that ordinate does not start at zero.

Fig. 3.

Infection reduced animal mean dendritic length, calculated by averaging all neurons from an individual animal. *P<0.05, Student’s t-test; n=4 animals each for control and infected group.

Fig. 4.

Infection did not affect dendritic length of pyriform cortex, thus precluding a generalized retraction all over the brain. Neurons were sampled from right pyriform cortex, using the same brain slices used for quantification of basolateral amygdala neurons. Dot and whiskers depict mean ± s.e.m. Box plots depict median, 25th percentile and 75th percentile; n=28 neurons for control and 16 neurons for infected. Neurons were derived from four control and four infected animals. Please note that ordinate does not start at zero.

Fig. 5.

Infection reduced circulating levels of plasma corticosterone, both at baseline and after exposure to bobcat urine. Dot and whiskers depict mean ± s.e.m. Box plots depict median, 25th percentile and 75th percentile. *P<0.0001, **P<0.01 compared with controls, using post-hoc Student’s t-test; n=8 control and 14 infected animals for baseline, and 8 control and 7 infected animals post-exposure to cat odor. Please note that left and right panel have dissimilar scales.