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False True False.Synaptic plasticity in the adult central nervous system is a fundamental property of neural circuits which controls learning and memory and is disrupted in many psychiatric and neurological diseases, including major depressive disorder (MDD). The proposed experiments use the mouse model of MDD, chronic social defeat stress (CSDS) to examine the role of dysregulation of neuronal nitric oxide synthase (nNOS) and associated downstream signaling mechanisms in the pathogenesis of depression. Our recent studies indicate that nNOS-derived NO promotes maturation of inhibitory synapses, which enhances synaptic strength. We hypothesize that disruption of the NO-LTP pathway causes a loss of inhibitory control over excitatory synapses, which contributes to the pathophysiology of depression. A number of studies have shown that the serotonin transporter (SERT) plays a critical role in antidepressant action. We hypothesize that NO-LTP inhibition of the SERT provides a novel mechanism by which antidepressants exert their action. We also hypothesize that NO-LTP inhibition of the SERT in the amygdala is responsible for the heightened anxiety observed in CSDS mice. The overarching goal of this project is to reveal the role of the NO-LTP pathway in the pathogenesis of depression, using mouse models of MDD. In Specific Aim 1, we will investigate whether inhibition of the NO-LTP pathway causes loss of inhibitory control over excitatory synapses, and contributes to the development of depression-like behavior. In Specific Aim 2, we will determine the role of the NO-LTP pathway in the regulation of the serotonin transporter, and its role in regulating depression-like behavior in mice exposed to CSDS. Finally, in Specific Aim 3, we will determine whether suppression of the NO-LTP pathway can serve as a potential target for the development of novel treatments for depression. PUBLIC HEALTH RELEVANCE: This research will use mouse models to investigate the role of a novel signaling pathway in the pathophysiology of major depressive disorder, using genetic and pharmacological approaches. The results from the proposed experiments will help to identify novel drug targets for the treatment of depression.Gambling is, of course, legal for the first time in many years. But the idea of getting into debt to play the slots on Las Vegas’ Strip is an idea that never went away.
When Congress set up the Federal Reserve, it set up a law that allowed banks to create money with the stroke of a pen. It created the ability of individuals to make unlimited loans to each other. We call this “fractional reserve banking.” The Fed just sits and waits for the bankers to create money. It is a system that is remarkably similar to the system that existed before the 1929 crash that began the Great Depression.
For example, JPMorgan Chase is allowed to make money by borrowing money from you and me. We can’t do that ourselves, but
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