Network model of fear extinction and renewal functional pathways

Bruchey, Aleksandra K.; Shumake, Jason; González-Lima, Francisco

doi:10.1016/j.neuroscience.2006.12.014

Cited by 31 publications

(25 citation statements)

References 96 publications

(104 reference statements)

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“…To test such interpretation requires modeling the causal influences between regions in a network, such as with path analysis (McIntosh and Gonzalez-Lima, 1991 The path analysis approach, also known as structural equation modeling (SEM) was first applied to brain mapping by McIntosh and Gonzalez-Lima (1991) in a study of auditory system FDG uptake following long-term habituation. SEM has since been used to analyze neural network interactions in other mapping studies using FDG, blood flow and fMRI data (e.g., McIntosh and Gonzalez-Lima, 1992, 1993, 1994, 1995Buchel and Friston, 1997;Bruchey et al, 2007). Another leading approach to analyze causal influences in brain networks is dynamic causal modeling (Penny et al 2004;Mechelli et al 2004).…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

“…SEM has since been used to analyze neural network interactions in other mapping studies using FDG, blood flow and fMRI data (e.g., McIntosh and Gonzalez-Lima, 1992, 1993, 1994, 1995Buchel and Friston, 1997;Bruchey et al, 2007). Another leading approach to analyze causal influences in brain networks is dynamic causal modeling (Penny et al 2004;Mechelli et al 2004).…”

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Functional networks underlying latent inhibition learning in the mouse brain

et al. 2007

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The present study reports the first comprehensive map of brain networks underlying latent inhibition learning and the first application of structural equation modeling to cytochrome oxidase data. In latent inhibition, repeated exposure to a stimulus results in a latent form of learning that inhibits subsequent associations with that stimulus. As neuronal energy demand to form learned associations changes, so does the induction of the respiratory enzyme cytochrome oxidase. Therefore, cytochrome oxidase can be used as an endpoint metabolic marker of the effects of experience on regional brain metabolic capacity. Quantitative cytochrome oxidase histochemistry was used to map brain regions in mice trained on a tone-footshock fear conditioning paradigm with either tone preexposure (latent inhibition), conditioning only (acquisition), conditioning followed by tone alone (extinction), or no handling or conditioning (naïve). The ventral cochlear nucleus, medial geniculate, CA1 hippocampus, and perirhinal cortex showed modified metabolic capacity due to latent inhibition. Structural equation modeling was used to determine the causal influences in an anatomical network of these regions and others thought to mediate latent inhibition, including the accumbens and entorhinal cortex. An uncoupling of ascending influences between auditory regions was observed in latent inhibition. There was also a reduced influence on the accumbens from the perirhinal cortex in both latent inhibition and extinction. The results suggest a specific network with a neural mechanism of latent inhibition that appears to involve sensory gating, as evidenced by modifications in metabolic capacity and effective connectivity between auditory regions and reduced perirhinal cortex influence on the accumbens. Keywords latent inhibition; metabolic mapping; structural equation modeling; cytochrome oxidase; sensory gating; perirhinal cortex; learning and memory In latent inhibition (LI), preexposure to a stimulus inhibits subsequent associations with that stimulus (Lubow and Moore, 1959). LI has been demonstrated in several behavioral paradigms in a variety of species, including humans, and is disrupted in schizophrenics (Lubow, 1989). Lesion and pharmacological studies have explored the neural mechanisms underlying LI and have identified several key brain regions. Conditioned drink suppression and eye blink conditioning studies demonstrated that lesions to the entorhinal cortex disrupt LI (Coutureau et al., 1999;Shohamy et al., 2000;Coutureau et al., 2002). Other studies using a conditioned Correspondence should be addressed to: Prof. F. Gonzalez-Lima, University of Texas at Austin, Department of Psychology, 1 University Station A8000, Austin, TX 78712-0187, USA. Phone (512) Fax (512) 471-4728, email: gonzalez-lima@mail.utexas.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will under...

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Functional networks underlying latent inhibition learning in the mouse brain

et al. 2007

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“…This finding may seem surprising since hippocampal function is clearly essential for contextual fear learning and we were studying cue learning. Yet, extinction of cue memories is context dependent and hippocampal activation is crucial for consolidation (transfer from short term to long term memory) of the extinguished memories (Bruchey et al, 2007). Therefore it seems that, in addition to uncoupling the correlation between basal amygdala activation and extinction acquisition, stress during adolescence may also lead to hyper-activation of the hippocampus when the animal undergoes learning in new context.…”

Section: Peri-pubertal Stress Impacts Brain Metabolism During Fear Exmentioning

confidence: 99%

“…The majority of previous rodent studies of metabolic activation during extinction focused on males (Bruchey et al, 2007;Hefner et al, 2008;Herry & Mons, 2004;Muigg et al, 2008). The use of male and female rats in our study enabled us to investigate whether the effects of peri-pubertal stress were sex-specific.…”

Section: Sex-related Differences In Brain Metabolic Activation Duringmentioning

confidence: 99%

“…This is possible because, during glycolysis, 2DG is trapped within active brain cells when it is phosphorylated by hexokinase (Sokoloff et al, 1977). So far, the majority of studies imaging metabolic activation during extinction in rodents have focused on males (mainly adults) (Bruchey, Shumake, & Gonzalez-Lima, 2007;Hefner et al, 2008;Herry & Mons, 2004;Muigg et al, 2008). Yet it is becoming increasingly clear that females differ from males in their morphological and behavioral responses to stress and brain response to various stimuli (Garrett & Wellman, 2009;Maeng, Waddell, & Shors, 2010).…”

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Stress during puberty boosts metabolic activation associated with fear-extinction learning in hippocampus, basal amygdala and cingulate cortex

Toledo-Rodriguez

Paus

Sandi

2012

Neurobiology of Learning and Memory

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a b s t r a c tAdolescence is characterized by major developmental changes that may render the individual vulnerable to stress and the development of psychopathologies in a sex-specific manner. Earlier we reported lower anxiety-like behavior and higher risk-taking and novelty seeking in rats previously exposed to peripubertal stress. Here we studied whether peri-pubertal stress affected the acquisition and extinction of fear memories and/or the associated functional engagement of various brain regions, as assessed with 2-deoxyglucose. We showed that while peri-pubertal stress reduced freezing during the acquisition of fear memories (training) in both sexes, it had a sex-specific effect on extinction of these memories. Moreover hippocampus, basal amygdala and cingulate and motor cortices showed higher metabolic rates during extinction in rats exposed to peri-pubertal stress. Interestingly, activation of the infralimbic cortex was negatively correlated with freezing during extinction only in control males, while only males stressed during puberty showed a significant correlation between behavior during extinction and metabolic activation of hippocampus, amygdala and paraventricular nucleus. No correlations between brain activation and behavior during extinction were observed in females (control or stress). These results indicate that exposure to peri-pubertal stress affects behavior and brain metabolism when the individual is exposed to an additional stressful challenge. Some of these effects are sex-specific.

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Fear Extinction in Rodents

et al. 2009

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Pavlovian conditioning paradigms have become important model systems for understanding the neuroscience of behavior. In particular, studies of the extinction of Pavlovian fear responses are yielding important information about the neural substrates of anxiety disorders in humans. These studies are germane to understanding the neural mechanisms underlying behavioral interventions that suppress fear, including exposure therapy. This chapter described detailed behavioral protocols for examining the nature and properties of fear extinction in laboratory rodents.Extinction of classical fear conditioning refers to a reduction in conditional responding after the repeated presentation of a conditioned stimulus (CS, usually a tone) in the absence of the unconditioned stimulus (US, usually a footshock) with which it was previously paired [see Wehner and Radcliffe (2004) for a chapter concerning fear conditioning procedures]. Interestingly, extinguished fear can be recovered in a number of situations. It can re-emerge with the passage of time after extinction (spontaneous recovery), as a result of a change in experimental context (renewal effect), or from an unsignaled presentation of the US (reinstatement effect). These observations suggest that extinction is a new learning process, and the fear reduction results from inhibition rather than erasure of the original fear memory. Moreover, unlike fear conditioning, extinction is highly context specific (for reference see Bouton et al., 2006;Ji and Maren, 2007).Because knowledge of the conditions that facilitate extinction learning may help to optimize extinction-based exposure therapies for the treatment of anxiety disorders, such as panic disorder and posttraumatic stress disorder (PTSD, the behavioral and neural mechanisms of fear extinction have attracted increasing attention over the last 20 years (Hermans et al., 2006). It has been shown that fear extinction engages several brain structures, including the amygdala, hippocampus and prefrontal cortex (see Ji and Maren, 2007;Quirk and Mueller, 2008). Typical methods for conducting an extinction experiment are presented below. Procedures for fear extinction are first described (see "Basic Protocol"), followed by alternative procedures including renewal (see "Alternative Protocol 1"), spontaneous recovery (see "Alternative Protocol 2"), and reinstatement (see "Alternative Protocol 3"). Basic Protocol: Fear extinction in ratsThis protocol uses freezing behavior in rats to index the acquisition and extinction of learned fear. It is important to point out that the conditioning and extinction of fear exhibits similar properties in several species (e.g., rats, mice, rabbits, cats) and using many different response measures (e.g., acoustic startle, bar press suppression, heart rate, etc.). Typically, extinction experiments require 8 to 16 subjects for appropriate statistical power. The protocol we describe makes use of automated methods for assessing freezing behavior,

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Network model of fear extinction and renewal functional pathways

Cited by 31 publications

References 96 publications

Functional networks underlying latent inhibition learning in the mouse brain

Functional networks underlying latent inhibition learning in the mouse brain

Stress during puberty boosts metabolic activation associated with fear-extinction learning in hippocampus, basal amygdala and cingulate cortex

Fear Extinction in Rodents

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