Single-Unit Activity in the Medial Prefrontal Cortex during Immediate and Delayed Extinction of Fear in Rats

Abstract

Delivering extinction trials minutes after fear conditioning yields only a short-term fear suppression that fully recovers the following day. Because extinction has been reported to increase CS-evoked spike firing and spontaneous bursting in the infralimbic (IL) division of the medial prefrontal cortex (mPFC), we explored the possibility that this immediate extinction deficit is related to altered mPFC function. Single-units were simultaneously recorded in rats from neurons in IL and the prelimbic (PrL) division of the mPFC during an extinction session conducted 10 minutes (immediate) or 24 hours (delayed) after auditory fear conditioning. In contrast to previous reports, IL neurons exhibited CS-evoked responses early in extinction training in both immediate and delayed conditions and these responses decreased in magnitude over the course of extinction training. During the retention test, CS-evoked firing in IL was significantly greater in animals that failed to acquire extinction. Spontaneous bursting during the extinction and test sessions was also different in the immediate and delayed groups. There were no group differences in PrL activity during extinction or retention testing. Alterations in both spontaneous and CS-evoked neuronal activity in the IL may contribute to the immediate extinction deficit.

Transcranial direct current stimulation may modulate extinction memory in posttraumatic stress disorder

“…Support for this idea can be found in animal studies where inactivation of the rodent vmPFC immediately after extinction training impaired memory for extinction (Burgos‐Robles, Vidal‐Gonzalez, Santini, & Quirk, 2007; Hikind & Maroun, 2008; Laurent & Westbrook, 2008; Sotres‐Bayon, Diaz‐Mataix, Bush, & LeDoux, 2009). Furthermore, extinction success is associated with the amount of high frequency bursting in rodent vmPFC neurons during (Chang, Berke, & Maren, 2010) as well as after extinction training (Burgos‐Robles et al., 2007). Applied to our findings, tDCS immediately following extinction learning may have augmented extinction consolidation, and moderately improved extinction memory observed by slightly lower SCR during early extinction recall.…”

Dopamine D1 Receptor Activation Rescues Extinction Impairments in Low-Estrogen Female Rats and Induces Cortical Layer-Specific Activation Changes in Prefrontal–Amygdala Circuits

“…Previous studies that measured neural activation through immediate-early gene expression (Zeidan et al, 2011), electrophysiological recordings (Milad and Quirk, 2002), or functional imaging (Phelps et al, 2004) indicate a relatively straightforward relationship between activity in IL (in rodents) or vmPFC (in humans) and successful extinction retrieval (but see Chang et al, 2010). In these studies, an increase in IL or vmPFC activity correlated with a decrease in fear expression, suggesting that when activated, IL/vmPFC neurons are more effective at suppressing amygdala activity.…”

Resolving the neural circuits of anxiety

“…By contrast, extinction of the learned fear association increases activity in BA neurons targeting the IL 105 . Fittingly, increased activity in the IL is associated with fear extinction 108 (but see also [109][110][111], and electrical stimulation of IL reduces freezing to the CS, even in animals that are resistant to extinction training 108,112 . In naïve mice, both of these subdivisions of mPFC exert similar levels of excitation and feed-forward inhibition upon BLA principal neurons.…”