Fear is a normal reaction to danger, but when fear response are routinely expressed inappropriately, a fear or anxiety disorder exists. One of the leading ideas is that anxiety disorders reflect malfunctions in the brain system that evolved to detect danger and execute defense responses. Many of the stimuli that activate this system, the fear system, in humans are not hard-wired into the brain s circuitry, but instead are learned about through experience. The proposed research is thus aimed at understanding how the brain learns and stores information about danger. Classical fear conditioning is used as a behavioral procedure through which an innocuous stimulus (a conditioned stimulus) when associated with an aversive event (an unconditioned stimulus), acquires the capacity to elicit fear reactions. The hypothesis being tested is that the amygdala plays an essential role in the plasticity that underlies fear conditioning. This hypothesis is supported by considerable evidence, but some fundamental questions concerning its validity remain unanswered.
The aims of this proposal are to clarify issues concerning the neural pathways which an acoustic conditioned stimulus is transmitted to the amygdala, the patterns of information flow within the amygdala, the necessity of the amygdala for the acquisition and storage process, and the nature of neural coding in various components of the circuitry. Together, these studies represent an integrated, multidisciplinary research program aimed at understanding the nature of fear and will hopefully provide information that will be useful in preventing or treating disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37MH038774-17
Application #
6391875
Study Section
Cognitive Functional Neuroscience Review Committee (CFN)
Program Officer
Anderson, Kathleen C
Project Start
1989-09-01
Project End
2003-05-31
Budget Start
2001-06-01
Budget End
2002-05-31
Support Year
17
Fiscal Year
2001
Total Cost
$302,859
Indirect Cost
Name
New York University
Department
Neurology
Type
Schools of Arts and Sciences
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
Dallérac, Glenn; Graupner, Michael; Knippenberg, Jeroen et al. (2017) Updating temporal expectancy of an aversive event engages striatal plasticity under amygdala control. Nat Commun 8:13920
Cowansage, Kiriana K; Bush, David E A; Josselyn, Sheena A et al. (2013) Basal variability in CREB phosphorylation predicts trait-like differences in amygdala-dependent memory. Proc Natl Acad Sci U S A 110:16645-50
Isogawa, Koichi; Bush, David E A; LeDoux, Joseph E (2013) Contrasting effects of pretraining, posttraining, and pretesting infusions of corticotropin-releasing factor into the lateral amygdala: attenuation of fear memory formation but facilitation of its expression. Biol Psychiatry 73:353-9
Schiller, Daniela; Raio, Candace M; Phelps, Elizabeth A (2012) Extinction training during the reconsolidation window prevents recovery of fear. J Vis Exp :e3893
Hoeffer, Charles A; Cowansage, Kiriana K; Arnold, Elizabeth C et al. (2011) Inhibition of the interactions between eukaryotic initiation factors 4E and 4G impairs long-term associative memory consolidation but not reconsolidation. Proc Natl Acad Sci U S A 108:3383-8
Diaz-Mataix, Lorenzo; Debiec, Jacek; LeDoux, Joseph E et al. (2011) Sensory-specific associations stored in the lateral amygdala allow for selective alteration of fear memories. J Neurosci 31:9538-43
Debiec, Jacek; Bush, David E A; LeDoux, Joseph E (2011) Noradrenergic enhancement of reconsolidation in the amygdala impairs extinction of conditioned fear in rats--a possible mechanism for the persistence of traumatic memories in PTSD. Depress Anxiety 28:186-93
Johnson, Luke R; Hou, Mian; Prager, Eric M et al. (2011) Regulation of the Fear Network by Mediators of Stress: Norepinephrine Alters the Balance between Cortical and Subcortical Afferent Excitation of the Lateral Amygdala. Front Behav Neurosci 5:23
Schiller, Daniela; Monfils, Marie-H; Raio, Candace M et al. (2010) Preventing the return of fear in humans using reconsolidation update mechanisms. Nature 463:49-53
Nedelescu, Hermina; Kelso, Catherine M; Lázaro-Muñoz, Gabriel et al. (2010) Endogenous GluR1-containing AMPA receptors translocate to asymmetric synapses in the lateral amygdala during the early phase of fear memory formation: an electron microscopic immunocytochemical study. J Comp Neurol 518:4723-39

Showing the most recent 10 out of 100 publications