The research proposes to investigate physiological and pharmacological mechanisms of classical conditioning using the potentiated startle effect, where acoustic startle amplitude in rats is increased in the presence of a light previously paired with a shock. In this paradigm conditioning is measured by the conditioned stimulus's (CS) effect on a reflex (acoustic startle). In the rat, the latency of acoustic startle is 8 msec. in the hindleg. We have delineated the neural pathway that mediates startle. To test where CS presentation modulates transmission along this pathway, startle will be elicited electrically at various points along the startle circuit before and after CS presentation in trained rats or control rats in which lights and shocks were randomly paired. To determine how complex the 'conditioned circuit' might be rats will be conditioned and then in testing the interval between light onset and tone onset will be varied to determine the minimum time the CS has to be on before startle is potentiated. Preliminary evidence indicates that only about 20 msec. may be required. Given retinal delays, this suggests an extraordinarily short transit time between activation of retinal ganglion cells and modification of acoustic startle. Finally, to determine the neurotransmitters involved in the expression of potentiated startle, selected drugs will be administered systemically or locally shortly before testing to see if they block or change potentiated startle.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS018033-07
Application #
3398087
Study Section
Biopsychology Study Section (BPO)
Project Start
1983-01-01
Project End
1989-12-31
Budget Start
1989-01-01
Budget End
1989-12-31
Support Year
7
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Liang, K C; Melia, K R; Miserendino, M J et al. (1992) Corticotropin-releasing factor: long-lasting facilitation of the acoustic startle reflex. J Neurosci 12:2303-12
Liang, K C; Melia, K R; Campeau, S et al. (1992) Lesions of the central nucleus of the amygdala, but not the paraventricular nucleus of the hypothalamus, block the excitatory effects of corticotropin-releasing factor on the acoustic startle reflex. J Neurosci 12:2313-20
Sananes, C B; Davis, M (1992) N-methyl-D-aspartate lesions of the lateral and basolateral nuclei of the amygdala block fear-potentiated startle and shock sensitization of startle. Behav Neurosci 106:72-80
Davis, M (1992) The role of the amygdala in fear and anxiety. Annu Rev Neurosci 15:353-75
Rosen, J B; Hitchcock, J M; Miserendino, M J et al. (1992) Lesions of the perirhinal cortex but not of the frontal, medial prefrontal, visual, or insular cortex block fear-potentiated startle using a visual conditioned stimulus. J Neurosci 12:4624-33
Davis, M (1992) The role of the amygdala in fear-potentiated startle: implications for animal models of anxiety. Trends Pharmacol Sci 13:35-41
Melia, K R; Davis, M (1991) Effects of septal lesions on fear-potentiated startle, and on the anxiolytic effects of buspirone and diazepam. Physiol Behav 49:603-11
Kehne, J H; Boulis, N M; Davis, M (1991) Effects of the phosphodiesterase inhibitor rolipram on the acoustic startle response in rats. Psychopharmacology (Berl) 105:27-36
Campeau, S; Hayward, M D; Hope, B T et al. (1991) Induction of the c-fos proto-oncogene in rat amygdala during unconditioned and conditioned fear. Brain Res 565:349-52
Boulis, N M; Kehne, J H; Miserendino, M J et al. (1990) Differential blockade of early and late components of acoustic startle following intrathecal infusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or D,L-2-amino-5-phosphonovaleric acid (AP-5). Brain Res 520:240-6

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