title: Functional MRI to assess alterations of functional networks in response to pharmacological or genetic manipulations of the serotonergic system in mice.
abstract: Imaging methods that enable the investigation of functional networks both in human and animal brain provide important insights into mechanisms underlying pathologies including psychiatric disorders. Since the serotonergic receptor 1A (5-HT(1A)-R) has been strongly implicated in the pathophysiology of depressive and anxiety disorders, as well as in the action of antidepressant drugs, we investigated brain connectivity related to the 5-HT(1A)-R system by use of pharmacological functional magnetic resonance imaging in mice. We characterized functional connectivity elicited by activation of 5-HT(1A)-R and investigated how pharmacological and genetic manipulations of its function may modulate the evoked connectivity. Functional connectivity elicited by administration of the 5-HT(1A)-R agonist 8-OH-DPAT can be described by networks characterized by small-world attributes with nodes displaying highly concerted response patterns. Circuits identified comprised the brain structures known to be involved in stress-related disorders (e.g. prefrontal cortex, amygdala and hippocampus). The results also highlight the dorsomedial thalamus, a structure associated with fear processing, as a hub of the 5-HT(1A)-R functional network. Administration of a specific 5-HT(1A)-R antagonist or use of heterozygous 5-HT(1A)-R knockout mice significantly reduced functional connectivity elicited by 8-OH-DPAT. Whole brain functional connectivity analysis constitutes an attractive tool to characterize impairments in neurotransmission and the efficacy of pharmacological treatment in a comprehensive manner.
authors: Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland.
authors: Florence
authors: F
authors: Razoux
authors: Christof
authors: C
authors: Baltes
authors: Thomas
authors: T
authors: Mueggler
authors: Aline
authors: A
authors: Seuwen
authors: Holger
authors: H
authors: Russig
authors: Isabelle
authors: I
authors: Mansuy
authors: Markus
authors: M
authors: Rudin
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008297:Male; D001523:Mental Disorders / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics* / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin