Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats.

Abstract

The emotional reactivity of rats with lesions of the dorsal portion of medial prefrontal cortex (mPFC) was examined using a classical fear conditioning paradigm. Conditioned fear behavior (freezing responses) was measured during both the acquisition and extinction phases of the task. Lesions enhanced fear reactivity to both the conditioned stimlulus (CS) and contextual stimuli during both phases, suggesting that dorsal mPFC lesions produce a general increase in fear reactivity in response to fear conditioning. M. A. Morgan, L. M. Romanski, and J. E. LeDoux (1993) found that lesions just ventral to the present lesions had no effect during acquisition of the same task and prolonged the fear response to the CS (but not the context) during extinction. Thus, both dorsal and ventral regions of mPFC are involved in the fear system, but each modulates different aspects of fear responsivity. The prefrontal cortex contains a number of anatomically and functionally distinct subregions, one of which is the midline area, the medial prefrontal cortex (mPFC; see Kolb, 1990, for review). There is now strong evidence that mPFC is involved in emotional processes (Divac, Mogenson, Blanchard,

Systemic administration of the benzodiazepine receptor partial inverse agonist FG‐7142 disrupts corticolimbic network interactions

“…These results suggest that both descending corticoamygdaloid and ascending amygdalocortical pathways play a critical role in forming affectively significant associations during aversive learning (Laviolette et al, 2005). Interestingly, prior acute or chronic stress interferes with the subsequent extinction of fear conditioning or the recall of extinction learning (Izquierdo et al, 2006;Miracle et al, 2006), processes mediated by both mPFC (Milad and Quirk, 2002;Morgan and LeDoux, 1995;Quirk et al, 2000) and BLA (Chhatwal et al, 2005;Falls et al, 1992;Walker et al, 2002). Thus, the FG-7142-induced disruption of synchronized activity within and between mPFC and BLA reported in the present study may provide a useful model for examining the effects of stressors on corticolimbic interactions.…”

Prefrontocortical Dopamine Loss in Rats Delays Long-Term Extinction of Contextual Conditioned Fear, and Reduces Social Interaction Without Affecting Short-Term Social Interaction Memory

“…Among these regions, the medial prefrontal cortex (mPFC) has extensive bidirectional connections with the hippocampus and amygdala, which supports a role of this structure on mnesic processes (Goldman-Rakic et al, 1984;von Hoesen et al, 1972von Hoesen et al, , 1975. Thus, the medial part has been proposed to participate in short-term object memory in rats and monkeys (Kowalska et al, 1991), and the lesion of this region is also known to interfere with the extinction of cued conditioned fear responses (Morgan et al, 1993;Morgan and LeDoux, 1995;Quirk et al, 2000), although negative results have also been reported (Gewirtz et al, 1997). The role of the mPFC in contextual conditioned fear, a type of memory that is dependent on both hippocampal and amygdala function, has been little explored, and it is known that prefrontocortical lesions do not affect acquisition and extinction of contextual conditioned fear (Morgan et al, 1993).…”

The neurobiology of retinoic acid in affective disorders

“…Patients with orbitofrontal damage also have impairments in impulse control with increased violent aggression and impairments in emotional regulation (Bechara et al 1994;Berlin et al 2004). Animals with lesions of the medial prefrontal cortex have an impaired ability to regulate emotional responding (Morgan and LeDoux 1995;Morgan et al 1993). Patients with depression were found to have a loss of glia and/or neurons in the orbitofrontal cortex (Rajkowska et al 1999) and other related parts of the medial prefrontal cortex, including subgenual cortex (Ongur et al 1998).…”