Gating of Fear in Prelimbic Cortex by Hippocampal and Amygdala Inputs

• Published in: Neuron (Cambridge, Mass.) Vol. 76; no. 4; pp. 804 - 812
• Main Authors: Sotres-Bayon, Francisco, Sierra-Mercado, Demetrio, Pardilla-Delgado, Enmanuelle, Quirk, Gregory J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.11.2012; Elsevier Limited
• Subjects: Acoustic Stimulation; Action Potentials - drug effects; Amygdala - drug effects; Amygdala - physiology; Analysis of Variance; Animals; Behavior, Animal - drug effects; Brain; Classification; Electrodes; Electroshock - methods; Fear - drug effects; GABA-A Receptor Agonists - pharmacology; Hippocampus - drug effects; Hippocampus - physiology; Male; Muscimol - pharmacology; Neural Pathways - drug effects; Neural Pathways - physiology; Neurons; Neurons - drug effects; Neurons - physiology; Prefrontal Cortex - cytology; Prefrontal Cortex - physiology; Rats; Rats, Sprague-Dawley; Rodents; Sensory Gating - drug effects; Sensory Gating - physiology; Statistics, Nonparametric
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2012.09.028

The prefrontal cortex (PFC) regulates emotional responses, but it is unclear how PFC integrates diverse inputs to select the appropriate response. We therefore evaluated the contribution of basolateral amygdala (BLA) and ventral hippocampus (vHPC) inputs to fear signaling in the prelimbic (PL) cortex, a PFC region critical for the expression of conditioned fear. In conditioned rats trained to press for food, BLA inactivation decreased the activity of projection cells in PL, and reduced PL conditioned tone responses. In contrast, vHPC inactivation decreased activity of interneurons in PL and increased PL conditioned tone responses. Consistent with hippocampal gating of fear after extinction, vHPC inactivation increased fear and PL pyramidal activity in extinguished, but not in conditioned, rats. These results suggest a prefrontal circuit whereby hippocampus gates amygdala-based fear. Thus, deficient hippocampal inhibition of PFC may underlie emotional disorders, especially in light of reduced hippocampal volume observed in depression and PTSD. [Display omitted] ► In behaving rats, BLA excites projection cells and vHPC excites interneurons in PL ► BLA promotes fear-signaling in PL, whereas vHPC inhibits it ► vHPC inhibits fear expression after, but not before, extinction ► vHPC gates fear expression via the PL after, but not before, extinction The prefrontal mechanism that integrates diverse inputs to select appropriate emotional responses is unclear. Sotres-Bayon et al. identify a prefrontal circuit that integrates competing input from the amygdala and hippocampus that is necessary for the control of fear behavior after extinction.