Neural systems involved in fear and anxiety will be studied using changes in the amplitude of the acoustic startle response, a short-latency reflex that can be elicited in all mammals. Acoustic startle can be increased by presentation of a brief light previously paired with shock (fear-potentiated startle), by sustained exposure to the same light even without prior light-shock pairings (light-enhanced startle), or by intraventricular infusion of corticotropin releasing hormone (CRH-enhanced startle). The PI and colleagues found that lesions or chemical inactivation of the bed nucleus of the stria terminalis (BNST) blocked light-enhanced or CRH-enhanced startle but not fear-potentiated startle. Conversely, lesions or chemical inactivation of the central nucleus of the amygdala blocked fear-potentiated startle but had no effect on light-enhanced or CRH-enhanced startle. The proposed experiments will further characterize similarities and differences between these structures in stress-induced enhancement of the startle reflex. Studies will test whether there is additivity of fear-potentiated startle, light-enhanced startle, and CRH-enhanced startle and whether intraventricular or local infusion into the BNST of the CRH antagonist alpha-helical CRH9-41 will block light-enhanced startle. Induction of c-fos in the amygdala vs. the BNST during presentation of a conditioned fear context vs. an unconditioned anxiogenic context will be measured. Other studies will measure how activation of CRH receptors in the BNST may ultimately increase startle at the level of the brainstem. This will be done by first delineating the neural pathway linking the BNST to the nucleus reticularis pontis caudalis. Previously, these investigators found that if rats were first given extensive overtraining and then given amygdala lesions, relearning could occur with further training. Other studies will evaluate whether the BNST can 'take over' for the amygdala in fear-potentiated startle using lesion, chemical inactivation and IC-fosI methodologies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH057250-02
Application #
2675661
Study Section
Psychobiology, Behavior, and Neuroscience Review Committee (PBN)
Project Start
1997-09-20
Project End
1998-08-31
Budget Start
1998-05-09
Budget End
1998-08-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Yale University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Davis, Michael; Walker, David L; Miles, Leigh et al. (2010) Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety. Neuropsychopharmacology 35:105-35
Walker, David; Yang, Yong; Ratti, Emiliangelo et al. (2009) Differential effects of the CRF-R1 antagonist GSK876008 on fear-potentiated, light- and CRF-enhanced startle suggest preferential involvement in sustained vs phasic threat responses. Neuropsychopharmacology 34:1533-42
Zhao, Zuowei; Yang, Yong; Walker, David L et al. (2009) Effects of substance P in the amygdala, ventromedial hypothalamus, and periaqueductal gray on fear-potentiated startle. Neuropsychopharmacology 34:331-40
Walker, D L; Miles, L A; Davis, M (2009) Selective participation of the bed nucleus of the stria terminalis and CRF in sustained anxiety-like versus phasic fear-like responses. Prog Neuropsychopharmacol Biol Psychiatry 33:1291-308
Heldt, Scott A; Davis, Michael; Ratti, Emiliangelo et al. (2009) Anxiolytic-like effects of the neurokinin 1 receptor antagonist GR-205171 in the elevated plus maze and contextual fear-potentiated startle model of anxiety in gerbils. Behav Pharmacol 20:584-95
Walker, David L; Davis, Michael (2008) Role of the extended amygdala in short-duration versus sustained fear: a tribute to Dr. Lennart Heimer. Brain Struct Funct 213:29-42
Walker, David L; Davis, Michael (2008) Amygdala infusions of an NR2B-selective or an NR2A-preferring NMDA receptor antagonist differentially influence fear conditioning and expression in the fear-potentiated startle test. Learn Mem 15:67-74
Lang, Peter J; Davis, Michael (2006) Emotion, motivation, and the brain: reflex foundations in animal and human research. Prog Brain Res 156:3-29
Josselyn, Sheena A; Falls, William A; Gewirtz, Jonathan C et al. (2005) The nucleus accumbens is not critically involved in mediating the effects of a safety signal on behavior. Neuropsychopharmacology 30:17-26
Zhao, Zuowei; Davis, Michael (2004) Fear-potentiated startle in rats is mediated by neurons in the deep layers of the superior colliculus/deep mesencephalic nucleus of the rostral midbrain through the glutamate non-NMDA receptors. J Neurosci 24:10326-34

Showing the most recent 10 out of 44 publications