Reduced anxiety and depression-like behavior in synaptotagmin IV (-/-) mice.
Synaptotagmin IV (Syt IV) is a secretory vesicle protein that is broadly expressed in brain and may function as a presynaptic regulator of synaptic release. Because Syt IV and abnormalities in neurotransmission have been implicated in psychiatric disease, we examined Syt IV (-/-) mice in animal models of mood-related behavior. We report that Syt IV (-/-) mice display lower levels of anxiety-like behavior in the elevated plus maze and enhanced locomotion in the open field. Syt IV (-/-) mice also exhibit reduced depression-like behavior and are highly sensitive to the effects of the anti-depressant imipramine in a modified Porsolt forced swim test. However, the physical restraint-induced stress hormone response is normal in Syt IV (-/-) mice. As judged by immunohistochemical criteria, the synaptic structure and connectivity of the hippocampus and raphe nucleus in Syt IV (-/-) mice are indistinguishable from wild-type littermates. These results indicate that Syt IV plays a role in rodent mood-related behavior and suggests Syt IV regulates synaptic function in the neuronal networks that modulate these behaviors.
Ferguson
Gregory D
GD
Department of Pharmacology, Health Sciences Building, University of Washington, Seattle, WA, Box 357280, 98195-7280, USA. gferguso@u.washington.edu
Herschman
Harvey R
HR
Storm
Daniel R
DR
D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D003863:Depression / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D007099:Imipramine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D050857:Synaptotagmins
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C494293:Syt4 protein, mouse; D050857:Synaptotagmins; D007099:Imipramine