Dissociable roles of prelimbic and infralimbic cortices, ventral hippocampus, and basolateral amygdala in the expression and extinction of conditioned fear

By Demetrio Sierra-Mercado, Nancy Padilla-Coreano, Gregory J. Quirk. Neuropsychopharmacology, 2010

1,122 citations recorded by the source corpus.

Current models of conditioned fear expression and extinction involve the basolateral amygdala (BLA), ventral medial prefrontal cortex (vmPFC), and the hippocampus (HPC). There is some disagreement with respect to the specific roles of these structures, perhaps due to subregional differences within each area. For example, growing evidence suggests that infralimbic (IL) and prelimbic (PL) subregions of vmPFC have opposite influences on fear expression. Moreover, it is the ventral HPC (vHPC), rather than the dorsal HPC, that projects to vmPFC and BLA. To help determine regional specificity, we used small doses of the GABAA agonist muscimol to selectively inactivate IL, PL, BLA, or vHPC in an auditory fear conditioning and extinction paradigm. Infusions were performed prior to extinction training, allowing us to assess the effects on both fear expression and subsequent extinction memory. Inactivation of IL had no effect on fear expression, but impaired the within-session acquisition of extinction as well as extinction memory. In contrast, inactivation of PL impaired fear expression, but had no effect on extinction memory. Inactivation of the BLA or vHPC impaired both fear expression and extinction memory. Post-extinction inactivations had no effect in any structure. We suggest a model in which amygdala-dependent fear expression is modulated by inputs from PL and vHPC, whereas extinction memory requires extinction-induced plasticity in IL, BLA, and/or vHPC.

Subfields: Behavioral Neuroscience, Cellular and Molecular Neuroscience, Cognitive Neuroscience

View Paper: https://www.semanticscholar.org/paper/e5e16f023c478d04813eef7d522fd3b3504e6faf

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Citations in the corpus

A temporal shift in the circuits mediating retrieval of fear memory (2015, background): “The conditioned group showed a significant increase in freezing compared to controls (F(5,25)= 40.”
Fear Extinction as a Model for Translational Neuroscience: Ten Years of Progress (2012, background): “Hippocampal inactivation reduces the expression of conditioned fear(Sierra-Mercado et al 2011), and prevents the renewal of fear after extinction (Ji & Maren 2005, Hobin et al 2006), both suggesting fear excitation.”
AMYGDALA MICROCIRCUITS CONTROLLING LEARNED FEAR (2014, background): “Extinction training also causes drastic changes in the CS responsiveness of BA neurons, consistent with the finding that BA inactivation impairs extinction (Herry et al., 2008; Amano et al., 2011; Sierra-Mercado et al., 2011; Livneh and Paz, 2012).”
Working Memory: Theories, Models, and Controversies (2015, neutral): “Hippocampal inactivation reduces the expression of conditioned fear (Sierra-Mercado et al. 2011) and prevents the BOLD: blood oxygen level–dependent renewal of fear after extinction (Hobin et al.”
Cannabidiol as a Potential Treatment for Anxiety Disorders (2015, background): “which drives expression of fear responses via connections with the amygdala [94], CBD had more complex effects: in unstressed rats, CBD was anxiogenic in the EPM, partially”