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Cellular Mechanism of Obsessive-Compulsive Disorder

dc.contributor.advisor Feng, Guoping Tee, Louis Yunshou 2015-05-12T20:43:59Z 2017-04-03T04:30:04Z 2015
dc.description.abstract <p>Obsessive-compulsive disorder (OCD) is a devastating illness that afflicts around 2% of the world's population with recurrent distressing thoughts (obsessions) and repetitive ritualistic behaviors (compulsions). While dysfunction at excitatory glutaminergic excitatory synapses leading to hyperactivity of the orbitofrontal cortex and head of the caudate - brain regions involved in reinforcement learning - are implicated in the pathology of OCD, clinical studies involving patients are unable to dissect the molecular mechanisms underlying this cortico-striatal circuitry defect. Since OCD is highly heritable, recent studies using mutant mouse models have shed light on the cellular pathology mediating OCD symptoms. These studies point toward a crucial role for deltaFosB, a persistent transcription factor that accumulates with chronic neuronal activity and is involved in various diseases of the striatum. Furthermore, elevated deltaFosB levels results in the transcriptional upregulation of Grin2b, which codes GluN2B, an N-methyl-D-aspartate glutamate receptor (NMDAR) subunit required for the formation and maintenance of silent synapses. Taken together, the current evidence indicates that deltaFosB-mediated expression of aberrant silent synapses in caudate medium spiny neurons (MSNs), in particular D1 dopamine-receptor expressing MSNs (D1 MSNs), mediates the defective cortico-striatal synaptic transmission that underlies compulsive behavior in OCD.</p>
dc.subject Neurosciences
dc.subject Psychobiology
dc.subject Cellular biology
dc.subject cellular mechanism
dc.subject deltaFosB
dc.subject NMDA receptor
dc.subject obsessive-compulsive disorder
dc.subject Sapap3 mutant mouse
dc.subject silent synapse
dc.title Cellular Mechanism of Obsessive-Compulsive Disorder
dc.type Dissertation
dc.department Neurobiology
duke.embargo.months 23

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