Abstract
Affective disorders, which include anxiety and depression, are highly prevalent and have overwhelming emotional and physical symptoms. Despite human brain imaging studies, which have implicated the prefrontal cortex including the anterior cingulate cortex (ACC), little is known about the ACC in anxiety disorders. Here we show that the ACC does modulate anxiety-like behavior in adult mice, and have identified a protein that is critical for this modulation. Absence of neurabin, a cytoskeletal protein, resulted in reduced anxiety-like behavior and increased depression-like behavior. Selective inhibition of neurabin in the ACC reproduced the anxiety but not the depression phenotype. Furthermore, loss of neurabin increased the presynaptic release of glutamate and cingulate neuronal excitability. These findings reveal novel roles of the ACC in anxiety disorders, and provide a new therapeutic target for the treatment of anxiety disorders.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anxiety / physiopathology*
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Anxiety Disorders / drug therapy
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Anxiety Disorders / physiopathology*
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Behavior, Animal
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Cells, Cultured
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Depressive Disorder / physiopathology
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GABA Modulators / pharmacology
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Gene Knockdown Techniques
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Gyrus Cinguli / cytology
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Gyrus Cinguli / physiology*
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Humans
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Male
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Mice
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Mice, Inbred C57BL
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism*
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Microinjections
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Midazolam / pharmacology
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neurons / cytology
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Neurons / metabolism
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Neuropsychological Tests
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Patch-Clamp Techniques
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Selective Serotonin Reuptake Inhibitors / therapeutic use
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Synaptic Transmission / physiology
Substances
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GABA Modulators
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Microfilament Proteins
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Nerve Tissue Proteins
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RNA, Small Interfering
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Serotonin Uptake Inhibitors
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neurabin
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Midazolam