Threatening or aversive experiences can produce enduring fear memories that last a lifetime. Indeed, rather than normal forgetting, fear memories may incubate becoming more intense as time passes. In addition, the triggers for old fear memories become less specific;as time passes fear becomes increasingly generalized to conditions that differ from the original context of the trauma. These three attributes of fear memory (enduring, incubating and generalizing) are no doubt major contributors to the fact that anxiety disorders are so prevalent in society and so debilitating to the individuals that suffer from them. The research proposed here is directed at the question of how the brain translates an experience into a permanent memory that increases in intensity (incubation) and becomes less specific over time (generalization). Our hypothesis is that, the enduring, incubating and generalizing attributes of fear memory require coordinated activity in several neural structures and it is this coordinated activity that gives traumatic memories these attributes. We propose 3 aims to answer the questions raised by this hypothesis: 1) Where in the overall fear network must activity occur to establish enduring, incubating and generalizing fear memory? To achieve this we will inactivate connections between the brain structures that comprise the network and determine which of these projections contribute to enduring fear. 2) When, in relationship to the threatening experience, must this activity occur? To answer this question we will inactivate the relevant pathways at specific times in relation to the trauma to determine if activity during acquisition, retention or recall is most important for these features of fear memory. 3) What is the nature of the activity that leads to the expression of the 3 attributes of enduring memory? We will image network activity at the single neuron level to determine what patterns of activity give rise to these powerful attributes of fear.

Public Health Relevance

Anxiety disorders are very common and very debilitating to both the individuals, and their families, that suffer from them. The debilitation arises because fear memories last a lifetime, while they increase in intensity and are triggered by less specific events. This grant seeks to determine how the brain creates memories with these attributes.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Neurobiology of Learning and Memory Study Section (LAM)
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Vicentic, Aleksandra
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University of California Los Angeles
Schools of Arts and Sciences
Los Angeles
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Ponnusamy, Ravikumar; Zhuravka, Irina; Poulos, Andrew M et al. (2016) Retrieval and Reconsolidation Accounts of Fear Extinction. Front Behav Neurosci 10:89
Poulos, Andrew M; Mehta, Nehali; Lu, Bryan et al. (2016) Conditioning- and time-dependent increases in context fear and generalization. Learn Mem 23:379-85
Fast, Cynthia D; Flesher, M Melissa; Nocera, Nathanial A et al. (2016) Learning history and cholinergic modulation in the dorsal hippocampus are necessary for rats to infer the status of a hidden event. Hippocampus 26:804-15
Perusini, Jennifer N; Meyer, Edward M; Long, Virginia A et al. (2016) Induction and Expression of Fear Sensitization Caused by Acute Traumatic Stress. Neuropsychopharmacology 41:45-57
Perusini, Jennifer N; Fanselow, Michael S (2015) Neurobehavioral perspectives on the distinction between fear and anxiety. Learn Mem 22:417-25
Poulos, Andrew M; Zhuravka, Irina; Long, Virginia et al. (2015) Sensitization of fear learning to mild unconditional stimuli in male and female rats. Behav Neurosci 129:62-7
Cushman, Jesse D; Moore, Mellissa D; Olsen, Richard W et al. (2014) The role of the δ GABA(A) receptor in ovarian cycle-linked changes in hippocampus-dependent learning and memory. Neurochem Res 39:1140-6
Zelikowsky, Moriel; Hersman, Sarah; Chawla, Monica K et al. (2014) Neuronal ensembles in amygdala, hippocampus, and prefrontal cortex track differential components of contextual fear. J Neurosci 34:8462-6
Kesner, Raymond P; Hui, Xu; Sommer, Taylor et al. (2014) The role of postnatal neurogenesis in supporting remote memory and spatial metric processing. Hippocampus 24:1663-71
Fanselow, Michael S; Zelikowsky, Moriel; Perusini, Jennifer et al. (2014) Isomorphisms between psychological processes and neural mechanisms: from stimulus elements to genetic markers of activity. Neurobiol Learn Mem 108:5-13

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