To measure anxiety in a mouse and suggest it’s similar to anxiety in a person may seem like a stretch, but the metrics sound uncannily familiar. Paralyzed by fear, afraid to leave the house or socialize with others, scared of new places, preferring the dark to the light of day.
Researchers at The Rockefeller University report this week that mice missing a particular gene show a big increase in these symptomatic behaviors. The scientists also show how the gene, Lynx2, alters the way brain cells communicate and say a similar process may underlie anxiety disorders in humans.
“I’d be surprised if these findings are not relevant to humans,” says Nathaniel Heintz, head of the Laboratory of Molecular Biology at Rockefeller, who led the research. “With structures relating to basic functions as evolutionarily ancient as fear and anxiety, I think you can learn a great deal from cross-species studies.”
Lynx2 produces molecules that influence communication between neurons in brain areas associated with anxiety. In prior work, the researchers showed that the gene generates a molecule called a mammalian prototoxin, an evolutionary precursor to snake venom toxins. The prototoxins target the same cells as snake venom but regulate their activity instead of inactivating them completely. To investigate exactly what Lynx2 does, Heintz and colleagues knocked out the gene in a line of mice and compared their behavior — and biochemistry — to that of a normal cohort. The bottom line: Mice lacking Lynx2 had no glaring defects, apart from being a very nervous breed.
Compared to regular mice, the jittery creatures spent less time in brightly illuminated spaces, preferring to hide in the dark. They were slower to explore a mysterious new space when presented the option. They chose to isolate themselves in an empty cage rather than socialize with a companion next door.
To study the brain-based cause of the odd behavior, Heintz, who is also a Howard Hughes Medical Institute investigator, collaborated with Paul Greengard, head of the Laboratory of Molecular and Cellular Neuroscience to perform a series of biochemical tests and single-cell electrical recordings. The results showed that a particular group of neurons in the genetically modified mice became more sensitive to nicotine. These neurons were in a key part of the medial prefrontal cortex, which projects to the amygdala, both brain structures known to be active in anxious people. The researchers speculate that this excitability may cause the anxious behavior in the mice lacking the Lynx2 gene, and that variation in this gene — which humans share — could play a role in human anxiety.
Now the scientists will knock out the gene in certain parts of the complex anxiety circuit in hopes of zeroing in on a single cell-type responsible for the behaviors in mice. “If we can find exactly what part of the circuit is responsible for the generalized anxiety we see here, in-depth studies of those cells might provide new avenues for development of effective treatments for common anxieties or social phobias,” Heintz says.
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Journal reference:
Ayse B. Tekinay, Yi Nong, Julie M. Miwa, Ivo Lieberam, Ines Ibanez-Tallon, Henry A. Lester, Paul Greengard and Nathaniel Heintz. A role for LYNX2 in anxiety-related behavior. Proceedings of the National Academy of Sciences
“You wait till Larry comes and I tell him my theory!” The bids, duly sealed, were given into the keeping of the commissary officer to be put in his safe, and kept until the day of judgment, when all being opened in public and in the presence of the aspirants, the lowest would[Pg 188] get the contract. It was a simple plan, and gave no more opportunity for underhand work than could be avoided. But there were opportunities for all that. It was barely possible—the thing had been done—for a commissary clerk or sergeant, desirous of adding to his pittance of pay, or of favoring a friend among the bidders, to tamper with the bids. By the same token there was no real reason why the commissary officer could not do it himself. Landor had never heard, or known, of such a case, but undoubtedly the way was there. It was a question of having the will and the possession of the safe keys. "Well, I believe our boys 's all right. They're green, and they're friskier than colts in a clover field, but they're all good stuff, and I believe we kin stand off any ordinary gang o' guerrillas. I'll chance it, anyhow. This's a mighty valuable train to risk, but it ought to go through, for we don't know how badly they may need it. You tell your engineer to go ahead carefully and give two long whistles if he sees anything dangerous." "Fine-looking lot of youngsters," he remarked. "They'll make good soldiers." "That's just what he was, the little runt, and we had the devil's own time finding him. What in Sam Hill did the Captain take him for, I'd like to know? Co. Q aint no nursery. Well, the bugler up at Brigade Headquarters blowed some sort of a call, and Skidmore wanted to know what it meant. They told him that it was an order for the youngest man in each company to come up there and get some milk for his coffee tomorrow morning, and butter for his bread. 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They asked why we didn't get the right kind of nurses for our company, that wouldn't let the members stray out of their sight? Why we didn't call the children in when the chickens went to roost, undress 'em, and tuck 'em in their little beds, and sing to 'em after they'd said 'Now I lay me down to sleep?' I stood it all until that big, hulking Pete Nasmith came down with a camp-kettle, which he was making ring like a bell, as he yelled out, 'Child lost! Child lost!' Behind him was Tub Rawlings singing, 'Empty's the cradle, baby's gone.' Then I pulled off my blouse and slung it into my tent, and told 'em there went my chevrons, and I was simply Scott Ralston, and able to lick any man in Co. A. One o' their Lieutenants came out and ordered them back to their quarters, and I deployed the company in a skirmish-line, and started 'em through the brush toward Brigade Headquarters. About three-quarters o' the way Osc Brewster and Ol Perry, when going through a thicket, heard a boy boo-hooing. 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Memory came, rather sick. He remembered the fight, his terror, the flaming straw, the crowd that constricted and crushed him like a snake. His rage and hate rekindled, but this time without focus—he hated just everyone and everything. He hated the wheels which jolted him, his body because it was bruised, the other bodies round him, the stars that danced above him, those unknown footsteps that tramped beside him on the road. Farewell to Jane and Caroline!" HoME大香蕉色人阁
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