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The Journal of Neuroscience, April 9, 2008, 28(15):4028-4036; doi:10.1523/JNEUROSCI.2623-07.2008

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Behavioral/Systems/Cognitive
Fear Conditioning and Extinction Differentially Modify the Intrinsic Excitability of Infralimbic Neurons

Edwin Santini,¹ Gregory J. Quirk,^2,3 and James T. Porter¹

¹Department of Pharmacology and Physiology, Ponce School of Medicine, Ponce, Puerto Rico 00732-7004, and Departments of ²Psychiatry and ³Anatomy and Neurobiology, School of Medicine, University of Puerto Rico, San Juan, Puerto Rico 00936

Correspondence should be addressed to Dr. Edwin Santini, Department of Pharmacology, Ponce School of Medicine, P.O. Box 7004, Ponce, Puerto Rico 00732-7004. Email: edsantini{at}yahoo.com

Extinction of conditioned fear is an active learning process involving inhibition of fear expression. It has been proposed that fear extinction potentiates neurons in the infralimbic (IL) prefrontal cortex, but the cellular mechanisms underlying this potentiation remain unknown. It is also not known whether this potentiation occurs locally in IL neurons as opposed to IL afferents. To determine whether extinction enhances the intrinsic excitability of IL pyramidal neurons in layers II/III and V, we performed whole-cell patch-clamp recordings in slices from naive, conditioned, or conditioned-extinguished rats. We observed that conditioning depressed IL excitability compared with slices from naive animals, as evidenced by a decreased number of spikes evoked by injected current and an increase in the slow afterhyperpolarizing potential (sAHP). Extinction reversed these conditioning-induced effects. Furthermore, IL neurons from extinguished rats showed increased burst spiking compared with naive rats, which was correlated with extinction recall. These changes were specific to IL prefrontal cortex and were not observed in prelimbic prefrontal cortex. Together, these findings suggest that IL intrinsic excitability is reduced to allow for expression of conditioning memory and enhanced for expression of extinction memory through the modulation of Ca²⁺-gated K⁺ channels underlying the sAHP. Inappropriate modulation of these intrinsic mechanisms may underlie anxiety disorders, characterized by exaggerated fear and deficient extinction.

Key words: amygdala; prelimbic; fear expression; medial prefrontal cortex; sAHP; bursting

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Received June 8, 2007; revised Feb. 21, 2008; accepted Feb. 22, 2008.

Correspondence should be addressed to Dr. Edwin Santini, Department of Pharmacology, Ponce School of Medicine, P.O. Box 7004, Ponce, Puerto Rico 00732-7004. Email: edsantini{at}yahoo.com

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