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
"'I'll make old vases for you if you want them—will make them just as I made these.' He had visions of a room full of golden brown beard. It was the most appalling thing he had ever witnessed, and there was no trickery about it. The beard had actually grown before his eyes, and it had now reached to the second button of the Clockwork man's waistcoat. And, at any moment, Mrs. Masters might return! "Worth stealing," a Society journalist lounging by remarked. "I could write a novel, only I can never think of a plot. Your old housekeeper is asleep long ago. Where do you carry your latchkey?" "Never lose your temper," he said. "It leads to apoplexy. Ah, my fine madam, you thought to pinch me, but I have pinched you instead." How does that strike you, Mr. Smith? Fancy Jerusha Abbott, (individually) ever pat me on the head, Daddy? I don't believe so-- The confusion was partly inherited from Aristotle. When discussing the psychology of that philosopher, we showed that his active Nous is no other than the idea of which we are at any moment actually conscious. Our own reason is the passive Nous, whose identity is lost in the multiplicity of objects with which it becomes identified in turn. But Aristotle was careful not to let the personality of God, or the supreme Nous, be endangered by resolving it into the totality of substantial forms which constitute Nature. God is self-conscious in the strictest sense. He thinks nothing but himself. Again, the subjective starting-point of305 Plotinus may have affected his conception of the universal Nous. A single individual may isolate himself from his fellows in so far as he is a sentient being; he cannot do so in so far as he is a rational being. His reason always addresses itself to the reason of some one else—a fact nowhere brought out so clearly as in the dialectic philosophy of Socrates and Plato. Then, when an agreement has been established, their minds, before so sharply divided, seem to be, after all, only different personifications of the same universal spirit. Hence reason, no less than its objects, comes to be conceived as both many and one. And this synthesis of contradictories meets us in modern German as well as in ancient Greek philosophy. 216 "I shall be mighty glad when we git this outfit to Chattanoogy," sighed Si. "I'm gittin' older every minute that I have 'em on my hands." "What was his name?" inquired Monty Scruggs. "Wot's worth while?" "Rose, Rose—my dear, my liddle dear—you d?an't mean——" "I'm out of practice, or I shouldn't have skinned myself like this—ah, here's Coalbran's trap. Perhaps he'll give you a lift, ma'am, into Peasmarsh." Chapter 18 "The Fair-pl?ace." "Yes," replied Black Jack, "here they are," drawing a parchment from his pocket. "This is the handwriting of a retainer called Oakley." HoME大桥未久AV手机在线观看
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