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Who moved my worm? Bird-food study by Cornell biologists shows role of brain's cannabinoid chemicals in dealing with change

ITHACA, N.Y. -- Some birds' already-amazing memories -- for the thousands of different spots where they cached their food -- can be further improved by blocking natural brain chemicals called cannabinoids, which resemble the active ingredient THC in marijuana.

But improved memory can be a liability for cannabinoid-free birds, Cornell University researchers have discovered: When their food is moved, birds without benefit of cannabinoids have trouble imagining where else the food might be.

The discovery is reported in the British journal, Proceedings of the Royal Society: Biological Sciences (Vol. 271, No. 1552, Oct. 7, 2004) under the title, "Cannabinoid Inhibition Improves Memory in Food-storing Birds."

Timothy J. DeVoogd, the Cornell professor of psychology and of neurobiology and behavior who led the study, comments: "Since marijuana is known to impair formation of new memories in people, perhaps an anti-cannabinoid drug like the one we used in this research might improve the retention of a new memory in people, just as it does in birds. However, this research suggests that enhanced memory retention might come with a cost -- the loss of the ability to change the memory. Perhaps the reason cannabinoid sensitivity exists in the brain is to provide a balance in memory, between accuracy and flexibility."

The Cornell biologists' study focused on food storage by black-capped chickadees (Poecile atricapilla ) and examined the function of a cannabinoid receptor called CB1-R in the bird's hippocampus, the same area of the brain used by humans for storing memories. CB1-R receptors react to changing levels of so-called endogenous cannabinoids, the natural hormones such as anadamide, circulating inside animals' bodies.

Cannabinoids were named for cannabis plants where the hormones were first identified. Since then, studies in other laboratories have suggested a variety of roles for the body's endogenous cannabinoid system -- ranging from pain control, reproduction, vision and immune function to learning, memory formation and retention. In the Cornell study, endogenous cannabinoids were blocked from reaching the birds' CB1-R receptors with a cannabinoid-antagonist drug called SR141716A.

For chickadees treated with anti-cannabinoid drugs and for "control" birds receiving a placebo treatment that allowed endogenous cannabinoids to reach their brain receptors, the assigned task was a simpler form of a food-storage exercise wild birds perform thousands of times each season -- remembering where bits of food were hidden. First the chickadees were allowed to find a mealworm that scientists had placed in one of 19 identical feeding holes. Then the lights went out and the birds returned to their nests. Seventy-two hours later, when the birds were released to visit the feeders, knotted string had been stuffed in all 19 feeding holes to conceal the worm.

Birds that had learned while on cannabinoid blockers were more successful at finding the hidden worm on the first try, while birds with endogenous cannabinoids reaching their brain receptors made more errors -- they pulled out several knotted strings before finding the food cache.

Then the scientists changed the game plan. They placed a worm in a different feeding hole, allowed all the birds to find the new location, and repeated the exercise. This time it was the cannabinoid-blocked birds that made more mistakes. They returned again and again to the hole where the first worm had been hidden. They frantically tugged on nearby knots to look for worms. But they couldn't seem to erase the memory of the first feeding hole and comprehend that the worm had been moved.

However, birds with free-flowing cannabinoids took the change in stride. They wasted little time searching for worms in the first location and easily moved on to the next site. They were better able to do what food-storing birds outside the laboratory do naturally -- "extinguish the previous memory trace and avoid revisiting emptied cache sites," as the biologists explained in their Proceedings report.

Cannabinoid signaling was allowing the control birds to overcome the source of errors made by the cannabinoid-blocked birds, the so-called proactive interference in which an old memory interferes with a new one, such that the birds cannot shift attention to new sites.

"It may be that both states of cannabinoid exposure, which we manipulated separately in our experiments, normally alternate in the same birds with such prodigious memories for food-storage sites," DeVoogd said. "Perhaps the endogenous cannabinoid system switches on and off, briefly reducing exposure to the chemical to help memories form, then increasing cannabinoid levels when the memory is no longer needed."

Also conducting the study, which was funded by the National Institutes of Health, were Alexander Z. Rankin, a Cornell undergraduate who is now in medical school at Loyola University; Michelle L. Tomaszycki, , a research associate at Cornell; and Michael W. Shiflett, who is now a researcher at the University of Pittsburgh.

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