The research team from Rockefeller and Columbia universities have found that mast cells, which have an important role to play in immune system, directly influence how mice respond to stressful situations.
Previous study by Columbia University scientists had shown that mast cells travel to the brain from other organs early on in development.
"We now knew that mast cells resided in the brain but we didn't know their function," said Rockefeller University's Donald Pfaff, head of the Laboratory of Neurobiology and Behavior.
"But we know that they synthesize a large number of important chemical mediators that could potentially have severe neurophysiological effects," he added.
The number of mast cells and anxiety levels in mice have been shown to ebb and flow with the onset of stressful conditions, including asthma and food allergies.
During the study, Pfaff and postdoc Ana Ribeiro, and the Columbia team, led by senior author Rae Silver and graduate student Kate Nautiyal bred mice that lacked mast cells and compared their behaviour in stressful situations to the behaviour of mice that had a full or a moderate arsenal of mast cells.
They sought to determine how willing the mice were to navigate open and lit environments and high spaces, which mice find anxiety-producing.
The mice were then placed in an elevated maze with four long arms - two simulated a canyon and the other two a cliff.
They found that mice that lacked mast cells preferred to stay in the canyons, entering and investigating the doors to the cliffs significantly fewer times than mice with mast cells.
When placed in a square box, mast cell-deficient mice preferred to scuttle against the walls, and were more hesitant to venture out to the center of the box than mice with mast cells.
They also defecated more, a physiological sign of anxiety. However, the genetically different mice did not show differences in overall arousal or locomotion, suggesting that their behavioral changes were specific to their anxious state.
In another experiment the researchers used a drug that prevents sack-like granules in mast cells from busting open and releasing the array of mood and immune regulators they contain, such as serotonin, histamine, and various biochemical mediators in the mice that had mast cells.
When the researchers targeted the drug to work specifically on mast cells in the brain, rather than in other organs, the mice showed much higher levels of anxiety-like behaviour during the tests, but showed no difference in other tested physiological responses.
The study appears in the Proceedings of the National Academy of Sciences.