The protozoan parasite Toxoplasma gondii blocks the innate aversion of rats for cat urine, instead producing an attraction to the pheromone; this may increase the likelihood of a cat predating a rat. This is thought to reflect adaptive, behavioral manipulation by Toxoplasma in that the parasite, although capable of infecting rats, reproduces sexually only in the gut of the cat. The ''behavioral manipulation'' hypothesis postulates that a parasite will specifically manipulate host behaviors essential for enhancing its own transmission. However, the neural circuits implicated in innate fear, anxiety, and learned fear all overlap considerably, raising the possibility that Toxoplasma may disrupt all of these nonspecifically. We investigated these conflicting predictions. In mice and rats, latent Toxoplasma infection converted the aversion to feline odors into attraction. Such loss of fear is remarkably specific, because infection did not diminish learned fear, anxiety-like behavior, olfaction, or nonaversive learning. These effects are associated with a tendency for parasite cysts to be more abundant in amygdalar structures than those found in other regions of the brain. By closely examining other types of behavioral patterns that were predicted to be altered we show that the behavioral effect of chronic Toxoplasma infection is highly specific. Overall, this study provides a strong argument in support of the behavioral manipulation hypothesis. Proximate mechanisms of such behavioral manipulations remain unknown, although a subtle tropism on part of the parasite remains a potent possibility.behavioral manipulation ͉ fear ͉ parasites ͉ predator T he ''behavioral manipulation'' hypothesis states that a parasite can alter host behavior specifically to increase its own transmission efficiency (1, 2). After an acute infection, the protozoan parasite Toxoplasma gondii latently persists in the brain for the life of an infected host, offering an opportunity to study the behavioral manipulation hypothesis (3). Toxoplasma reproduces sexually in a two-species life cycle (4). The sexual phase of its reproduction occurs in the feline intestine, from which highly stable oocysts are excreted in the feces. Grazing animals, including rodents, can then ingest these oocysts. In these hosts, Toxoplasma forms cysts and persists in the central nervous system. The life cycle is completed when a cat eats an infected animal. Recent reports indicate that the parasite blunts the innate aversion of rats for the urine of cats, converting this aversion to an attraction (5), although it does not interfere with energetically costly behaviors related to mating success and social status (6). These findings agree with the behavioral manipulation hypothesis, which predicts that parasites will alter only behaviors that are beneficial to their transmission while leaving other behaviors intact.Several studies have investigated the innate fear of laboratory rodents toward cat odors (7-11). These studies have delineated a neuroanatomical circuit comprising ...
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