Tissue plasminogen activator in the bed nucleus of stria terminalis regulates acoustic startle.
The bed nucleus of stria terminalis is a basal forebrain region involved in regulation of hormonal and behavioral responses to stress. In this report we demonstrate that bed nucleus of stria terminalis has a high and localized expression of tissue plasminogen activator, a serine protease with neuromodulatory properties and implicated in neuronal plasticity. Tissue plasminogen activator activity in the bed nucleus of stria terminalis is transiently increased in response to acute restraint stress or i.c.v. administration of a major stress mediator, corticotropin-releasing factor. We show that tissue plasminogen activator is important in bed nucleus of stria terminalis function using two criteria: 1, Neuronal activation in this region as measured by c-fos induction is reduced in tissue plasminogen activator-deficient mice; and 2, a bed nucleus of stria terminalis-dependent behavior, potentiation of acoustic startle by corticotropin-releasing factor, is attenuated in tissue plasminogen activator-deficient mice. These studies identify a novel site of tissue plasminogen activator expression in the mouse brain and demonstrate a functional role for this protease in the bed nucleus of stria terminalis.
Matys
T
T
Laboratory of Neurobiology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Pawlak
R
R
Strickland
S
S
D000161:Acoustic Stimulation; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D013216:Reflex, Startle / Q000502:physiology*; D012149:Restraint, Physical; D012686:Septal Nuclei / Q000378:metabolism / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
D017395:Plasminogen Activator Inhibitor 1; D016760:Proto-Oncogene Proteins c-fos; D003346:Corticotropin-Releasing Hormone; D010959:Tissue Plasminogen Activator; D003345:Corticosterone