Fear signaling in the prelimbic-amygdala circuit: a computational modeling and recording study

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...

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Bibliographic Details
Published in:Journal of neurophysiology 2013-08, Vol.110 (4), p.844-861
Main Authors: Pendyam, Sandeep, Bravo-Rivera, Christian, Burgos-Robles, Anthony, Sotres-Bayon, Francisco, Quirk, Gregory J, Nair, Satish S
Format: Article
Language:English
Subjects:
Acoustic Stimulation
Amygdala - physiology
Animals
Conditioning, Psychological - physiology
Fear - physiology
Male
Models, Neurological
Neural Pathways
Neurons - physiology
Prefrontal Cortex - physiology
Rats
Rats, Sprague-Dawley
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Summary: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.
ISSN:0022-3077
1522-1598
DOI:10.1152/jn.00961.2012