Abstract
Once acquired, a fearful memory can persist for a lifetime. Although learned fear can be extinguished, extinction memories are fragile. The resilience of fear memories to extinction may contribute to the maintenance of disorders of fear and anxiety, including post-traumatic stress disorder (PTSD). As such, considerable effort has been placed on understanding the neural circuitry underlying the acquisition, expression, and extinction of emotional memories in rodent models as well as in humans. A triad of brain regions, including the prefrontal cortex, hippocampus, and amygdala, form an essential brain circuit involved in fear conditioning and extinction. Within this circuit, the prefrontal cortex is thought to exert top-down control over subcortical structures to regulate appropriate behavioral responses. Importantly, a division of labor has been proposed in which the prelimbic (PL) and infralimbic (IL) subdivisions of the medial prefrontal cortex (mPFC) regulate the expression and suppression of fear in rodents, respectively. Here, we critically review the anatomical and physiological evidence that has led to this proposed dichotomy of function within mPFC. We propose that under some conditions, the PL and IL act in concert, exhibiting similar patterns of neural activity in response to aversive conditioned stimuli and during the expression or inhibition of conditioned fear. This may stem from common synaptic inputs, parallel downstream outputs, or cortico-cortical interactions. Despite this functional covariation, these mPFC subdivisions may still be coding for largely opposing behavioral outcomes, with PL biased towards fear expression and IL towards suppression.
Highlights
Pavlovian fear conditioning is a form of learning that serves as a robust model to explore the neurobiological underpinnings of disorders of fear and anxiety, including post-traumatic stress disorder (PTSD)
While Quirk et al (2000) suggest that IL neural activity is importantly involved in the consolidation of extinction memories, similar experiments have not replicated these effects insofar as medial prefrontal cortex (mPFC) lesions do not yield deficits in either conditioned inhibition or extinction learning under some conditions (Gewirtz et al, 1997; Garcia et al, 2006)
These findings suggest a high degree of similarity between both the structural and functional components of PL and IL, lending support to the hypothesis that these regions may covary as noted in several other reports (Baeg et al, 2001; Herry and Mons, 2004; Kim et al, 2010; Holmes et al, 2012; Halladay and Blair, 2015)
Summary
Pavlovian fear conditioning is a form of learning that serves as a robust model to explore the neurobiological underpinnings of disorders of fear and anxiety, including post-traumatic stress disorder (PTSD). While learned fear serves an adaptive purpose aiding survival, pathological fear states are thought to underlie various stress and trauma-related disorders such as PTSD, which has a lifetime prevalence of nearly 8% in the general population (Kessler et al, 1995, 2005). Not surprisingly, this number increases to as high as 30% in combat-exposed veterans (Koenen et al, 2008), amplifying the need for more effective therapies. We critically review the anatomical and physiological evidence that has led to this proposed dichotomy of function within mPFC, comparing results from rodents with those in humans
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