Fear Conditioning and Extinction Differentially Modify the Intrinsic Excitability of Infralimbic Neurons

Abstract

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 Ca 2ϩ -gated K ϩ channels underlying the sAHP. Inappropriate modulation of these intrinsic mechanisms may underlie anxiety disorders, characterized by exaggerated fear and deficient extinction.

Hippocampal–Prefrontal BDNF and Memory for Fear Extinction

“…Thus, following learning, hippocampal neurons may express BDNF initially, followed by BDNF expression in hippocampal targets such as mPFC and amygdala. Increased excitability in IL following extinction has been shown to predict extinction success (Burgos-Robles et al, 2007;Chang et al, 2010;Knapska and Maren, 2009;Santini et al, 2008). We observed that infusing BDNF into vHPC increased the firing rate of IL neurons, a vHPC target.…”

Dopamine D1versus D4Receptors Differentially Modulate the Encoding of Salient versus Nonsalient Emotional Information in the Medial Prefrontal Cortex

“…Although the present experiments focused primarily on the prelimbic (PLC) division of the mPFC, during the acquisition and expression (recall) phases of emotional associative memory, considerable evidence points to a functional dissociation between the prelimbic and infralimbic divisions of the mPFC during the acquisition versus extinction of emotional memory (Quirk and Mueller, 2008;Santini et al, 2008), such that neurons within the PLC appear critical for emotional memory acquisition whereas infralimbic neurons appear critical for extinction-related learning. The present results, although not directly examining the role of the infralimbic cortex in DA-related emotional memory acquisition and recall, also demonstrate an important role for the PLC in the encoding phase of emotional associative memory.…”

Dissociation of within- and between-Session Extinction of Conditioned Fear

“…Pharmacological blockade of CB1 abolished these effects. This is a striking observation, since the infralimbic cortex undergoes plastic changes during relearning/extinction training (Santini et al, 2008), which are thought to underlie its subsequent involvement in suppression of conditioned fear during extinction recall (Milad and Quirk, 2002). However, in light of the largely intact between-session extinction observed in mice with pharmacological blockade of CB1 (Fig.…”