Volume 17, Number 16,
Issue of August 15, 1997
pp. 6424-6433
Copyright ©1997 Society for Neuroscience
Role of the Septum in the Excitatory Effect of
Corticotropin-Releasing Hormone on the Acoustic Startle Reflex
Received Jan. 13, 1997; revised May 21, 1997; accepted May 29, 1997.
Younglim Lee and
Michael Davis
Department of Psychiatry, Yale University, New Haven, Connecticut
06508
Intracerebroventricular administration of corticotropin-releasing
hormone (CRH) elicits a constellation of behavioral, autonomic, and
endocrinological changes typically observed in stress. One of the
behavioral changes after intracerebroventricular CRH is a profound
increase of startle amplitude (CRH-enhanced startle). The present study
examined the role of the septum in CRH-enhanced startle. The septum has
direct and indirect connections to the amygdala and inhibits the
amygdala. Electrophysiological data show that CRH in the septum is
inhibitory. Therefore, it has been hypothesized that
intracerebroventricular CRH inhibits the septum, which in turn
disinhibits the amygdala, resulting in a constellation of changes via
activation of amygdala efferent targets. In testing this hypothesis, it
was found that electrolytic lesions of the medial septum, but not the
lateral septum, blocked CRH-enhanced startle. However, fiber-sparing
chemical lesions of the medial septum did not block CRH-enhanced
startle, suggesting that the blockade seen with the electrolytic
lesions was caused by damage to fibers of passage. A major fiber bundle
passing through the medial septum is the fornix, the primary efferent
pathway for the hippocampus. Fimbria transection blocked CRH-enhanced
startle almost completely, whereas the large electrolytic lesions of
the dorsal hippocampus did not block CRH-enhanced startle. Taken
together, these data suggest that perhaps the ventral hippocampus and
its efferent target areas, which communicate via the fimbria, may be
critically involved in CRH-enhanced startle.
Key words:
septum;
fimbria;
hippocampus;
corticotropin-releasing
hormone (CRH);
startle;
stress