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Parasite found to use sexy trick to fool rats into becoming cat food

Aug. 22, 2011
Courtesy of Stanford University
and World Science staff

A nor­mal male rat shows signs of fear when it smells cat urine. That makes sense, as a deadly pred­a­tor may be in the ar­ea. 

But a male rat in­fected with the par­a­site Tox­o­plasma re­acts to that same odor dif­fer­ent­ly, re­search­ers have found: a part of its brain be­comes ac­tive that char­ac­ter­is­tic­ally does so in the pres­ence of an ap­peal­ing female rat. 

Is it time to dim the lights and cue the Rach­ma­ni­noff for some cross-species canoodling?

Toxoplasma par­a­sites (green) are shown in­vad­ing nerve cells (red) in this lab­o­ra­to­ry set­up where flu­o­res­cently glow­ing mo­le­cules are used to color the cells and their parts. (Credit: I-Ping Lee)

Not real­ly, the re­search­ers say. In­stead, it seems the par­a­site is driv­ing the rat in­to the claws of a hun­gry cat. That en­ables the par­a­site to get in­to the fe­line gut, its breed­ing grounds.

"It's pos­si­ble the [rat] be­hav­ior we are see­ing in re­sponse to cat urine is sex­u­al at­trac­tion be­hav­ior, but we don't know that," said Pat­rick House, a doc­tor­al can­di­date in neu­ro­sci­ence at Stan­ford Uni­vers­ity in Cal­i­for­nia. "I would not say that they are de­fin­i­tively at­tracted, but they are cer­tainly less afraid. Re­gard­less, see­ing ac­ti­vity in the at­trac­tion path­way [of the rat brain] is bizarre."

A cat's small in­tes­tine is the only en­vi­ron­ment in which Tox­o­plasma can re­pro­duce sex­u­ally. Thus it ben­e­fits the par­a­site to trick its host rat in­to put­ting it­self in po­si­tion to get eat­en by the cat. No fear, no flight – and kit­ty's din­ner is served.

House, the lead au­thor of a pa­per on the find­ings pub­lished in the Aug. 17 is­sue of the re­search jour­nal PLoS One, works in the lab of Stan­ford neu­rol­o­gist Rob­ert Sapol­sky.

Sci­en­tists have known of Tox­o­plasma's ma­nipula­t­ion of rats for years, in­clud­ing the fact that in­fected rats seemed to lose their fear of cats. It’s an ex­am­ple of what is called the "ma­nipula­t­ion hy­poth­e­sis," which holds that some par­a­sites al­ter the be­hav­ior of their host or­gan­ism in a way that ben­e­fits the par­a­site. There are sev­er­al doc­u­mented ex­am­ples in in­sects.

But the de­tails of how the lit­tle single-celled pro­to­zo­an Tox­o­plasma, about a hun­dredth of a mil­li­me­ter long, ex­erts con­trol over the far more soph­is­t­icated rat have been a mys­tery.

Sapol­sky's group pre­vi­ously de­ter­mined that al­though the par­a­site in­fects the whole brain, it shows a pref­er­ence for a re­gion of the brain called the amyg­da­la, which is as­so­ci­at­ed with var­i­ous emo­tion­al states. Once in the brain, the par­a­site forms cysts around it­self, in which it es­sen­tially lies dor­mant.

House ran a se­ries of ex­pe­ri­ments with both healthy and Tox­o­plasma-in­fected rats. He ex­posed each male rat to ei­ther cat urine or a female rat in heat for 20 min­utes be­fore an­a­lyz­ing its brains for ev­i­dence of ex­cita­t­ion in the amyg­da­la. He used cat urine pur­chased in bulk from a whole­sal­er. No ac­tu­al cats par­ti­ci­pated in the ex­pe­ri­ments.

House an­a­lyzed cer­tain subre­gions of the amyg­da­la that fo­cus on in­nate fear and in­nate at­trac­tion. In healthy male rats, cat urine was found to ac­tivate the "fear" path­way. But in the in­fected rats, al­though there was still ac­ti­vity in the fear path­way, the urine prompted quite a bit of ac­ti­vity in the "at­trac­tion" path­way as well, he said, "ex­actly what you would see in a nor­mal rat ex­posed to a fema­le.”

"Tox­o­plasma is al­tering these cir­cuits in the amyg­da­la, mud­dling fear and at­trac­tion," he added. The find­ings fit with ob­serva­t­ions House made dur­ing the ex­pe­ri­ments, when he no­ticed that the in­fected rats did­n’t run when they smelled cat urine, but ac­tu­ally seemed drawn to it and spent un­usu­al amounts of time in­ves­ti­gat­ing it.

Al­though House said he does­n’t know how the cysts in the rats' brains are caus­ing the be­hav­ioral changes, he is im­pressed with what Tox­o­plasma can ac­com­plish. "There are not many or­gan­isms that can get in­to the brain, stay there and spe­cif­ic­ally per­turb your be­hav­ior," he said. "In some ways, Tox­o­plasma knows more about the neuro­bi­ol­o­gy of fear than we do, be­cause it can spe­cif­ic­ally al­ter it.”

Be­cause Tox­o­plasma re­pro­duces in the small in­tes­tine of cats, the par­a­sites are ex­cret­ed in fe­ces, which is pre­sumably how rats get in­fected. Rats are known to be ex­tremely cu­ri­ous, tast­ing al­most eve­ry­thing they come in con­tact with. Tox­o­plasma is al­so fre­quently found in fer­ti­liz­er and can in­fect vir­tu­ally any mam­mal.

About a third of all peo­ple har­bor Tox­o­plasma. For most, it seems harm­less, though it can be fa­tal in peo­ple with com­pro­mised im­mune sys­tems. It al­so can cross the pla­cen­tal bar­ri­er in a preg­nant wom­an and cre­ate many com­plica­t­ions, which is why preg­nant wom­en are ad­vised not to clean cat lit­ter boxes.

House said hu­mans ac­quire the par­a­site by eat­ing un­der­cooked meat or "eat­ing lit­tle bits of cat po­o­p, which I sus­pect hap­pens more of­ten than peo­ple want to ad­mit." Or know.

"There are a cou­ple doz­en stud­ies in the last few years show­ing that if you have schiz­o­phre­nia, you are more likely to have Tox­o­plasma. The stud­ies have­n't shown cause and ef­fect, but it's pos­si­ble," House said. "Hu­mans have amyg­da­lae too. We are afraid of and at­tracted to things – it's si­m­i­lar cir­cuit­ry."

* * *

A normal male rat shows signs of fear when it smells cat urine. That makes sense, as a deadly predator may be in the area. But a male rat infected with the parasite Toxoplasma reacts to that same odor differently, researchers have found: a part of its brain becomes active that characteristically does so in the presence of an appealing female rat. Is it time to dim the lights and cue the Rachmaninoff for some cross-species canoodling? Not really, the researchers say. Instead, it seems the parasite is driving the rat into the claws of a hungry cat. That enables the parasite to get into the feline gut, its breeding grounds. "It's possible the [rat] behavior we are seeing in response to cat urine is sexual attraction behavior, but we don't know that," said Patrick House, a doctoral candidate in neuroscience at Stanford University in California. "I would not say that they are definitively attracted, but they are certainly less afraid. Regardless, seeing activity in the attraction pathway [of the rat brain] is bizarre." A cat's small intestine is the only environment in which Toxoplasma can reproduce sexually. Thus it benefits the parasite to trick its host rat into putting itself in position to get eaten by the cat. No fear, no flight – and kitty's dinner is served. House, the lead author of a paper on the findings published in the Aug. 17 issue of the research journal PLoS One, works in the lab of Stanford neurologist Robert Sapolsky. Scientists have known of Toxoplasma's manipulation of rats for years, including the fact that infected rats seemed to lose their fear of cats. It’s an example of what is called the "manipulation hypothesis," which holds that some parasites alter the behavior of their host organism in a way that benefits the parasite. There are several documented examples in insects. But the details of how the little single-celled protozoan Toxoplasma, about a hundredth of a millimeter long, exerts control over the far more sophisticated rat have been a mystery. Sapolsky's group previously determined that although the parasite infects the whole brain, it shows a preference for a region of the brain called the amygdala, which is associated with various emotional states. Once in the brain, the parasite forms cysts around itself, in which it essentially lies dormant. House ran a series of experiments with both healthy and Toxoplasma-infected rats. He exposed each male rat to either cat urine or a female rat in heat for 20 minutes before analyzing its brains for evidence of excitation in the amygdala. He used cat urine purchased in bulk from a wholesaler. No actual cats participated in the experiments. House analyzed certain subregions of the amygdala that focus on innate fear and innate attraction. In healthy male rats, cat urine was found to activate the "fear" pathway. But in the infected rats, although there was still activity in the fear pathway, the urine prompted quite a bit of activity in the "attraction" pathway as well, he said, "exactly what you would see in a normal rat exposed to a female.” "Toxoplasma is altering these circuits in the amygdala, muddling fear and attraction," he added. The findings fit with observations House made during the experiments, when he noticed that the infected rats didn’t run when they smelled cat urine, but actually seemed drawn to it and spent unusual amounts of time investigating it. Although House said he doesn’t know how the cysts in the rats' brains are causing the behavioral changes, he is impressed with what Toxoplasma can accomplish. "There are not many organisms that can get into the brain, stay there and specifically perturb your behavior," he said. "In some ways, Toxoplasma knows more about the neurobiology of fear than we do, because it can specifically alter it.” Because Toxoplasma reproduces in the small intestine of cats, the parasites are excreted in feces, which is presumably how rats get infected. Rats are known to be extremely curious, tasting almost everything they come in contact with. Toxoplasma is also frequently found in fertilizer and can infect virtually any mammal. About a third of all people harbor Toxoplasma. For most, it seems harmless, though it can be fatal in people with compromised immune systems. It also can cross the placental barrier in a pregnant woman and create many complications, which is why pregnant women are advised not to clean cat litter boxes. House said humans acquire the parasite by eating undercooked meat or "eating little bits of cat poop, which I suspect happens more often than people want to admit." Or know. "There are a couple dozen studies in the last few years showing that if you have schizophrenia, you are more likely to have Toxoplasma. The studies haven't shown cause and effect, but it's possible," House said. "Humans have amygdalae too. We are afraid of and attracted to things – it's similar circuitry."