title: Fear signaling in the prelimbic-amygdala circuit: a computational modeling and recording study.
abstract: The acquisition and expression of conditioned fear depends on prefrontal-amygdala circuits. Auditory fear conditioning increases the tone responses of lateral amygdala neurons, but the increase is transient, lasting only a few hundred milliseconds after tone onset. It was recently reported that that the prelimbic (PL) prefrontal cortex transforms transient lateral amygdala input into a sustained PL output, which could drive fear responses via projections to the lateral division of basal amygdala (BL). To explore the possible mechanisms involved in this transformation, we developed a large-scale biophysical model of the BL-PL network, consisting of 850 conductance-based Hodgkin-Huxley-type cells, calcium-based learning, and neuromodulator effects. The model predicts that sustained firing in PL can be derived from BL-induced release of dopamine and norepinephrine that is maintained by PL-BL interconnections. These predictions were confirmed with physiological recordings from PL neurons during fear conditioning with the selective β-blocker propranolol and by inactivation of BL with muscimol. Our model suggests that PL has a higher bandwidth than BL, due to PL's decreased internal inhibition and lower spiking thresholds. It also suggests that variations in specific microcircuits in the PL-BL interconnection can have a significant impact on the expression of fear, possibly explaining individual variability in fear responses. The human homolog of PL could thus be an effective target for anxiety disorders.
authors.affiliation: Department of Electrical and Computer Engineering, University of Missouri, Columbia, Missouri 65211, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Pendyam
authors.forename: Christian
authors.initials: C
authors.lastname: Bravo-Rivera
authors.forename: Anthony
authors.initials: A
authors.lastname: Burgos-Robles
authors.forename: Francisco
authors.initials: F
authors.lastname: Sotres-Bayon
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Quirk
authors.forename: Satish S
authors.initials: SS
authors.lastname: Nair
mesh_terms: D000161:Acoustic Stimulation; D000679:Amygdala / Q000502:physiology*; D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology*; D008297:Male; D008959:Models, Neurological; D009434:Neural Pathways; D009474:Neurons / Q000502:physiology*; D017397:Prefrontal Cortex / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: fear conditioning; muscimol; neuromodulator; tone response