The role of the basolateral amygdala and infralimbic cortex in (re)learning extinction

Abstract

The basolateral amygdala complex (BLA) and infralimbic region of the prefrontal cortex (IL) play distinct roles in the extinction of Pavlovian conditioned fear in laboratory rodents. In the past decade, research in our laboratory has examined the roles of these brain regions in the re-extinction of conditioned fear: i.e., extinction of fear that is restored through re-conditioning of the conditioned stimulus (CS) or changes in the physical and temporal context of extinction training (i.e., extinction of renewed or spontaneously recovered fear). This paper reviews this research. It has revealed two major findings. First, in contrast to the acquisition of fear extinction, which usually requires neuronal activity in the BLA but not IL, the acquisition of fear re-extinction requires neuronal activity in the IL but can occur independently of neuronal activity in the BLA. Second, the role of the IL in fear extinction is determined by the training history of the CS: i.e., if the CS was novel prior to its fear conditioning (i.e., it had not been trained), the acquisition of fear extinction does not require the IL; if, however, the prior training of the CS included a series of CS-alone exposures (e.g., if the CS had been pre-exposed), the acquisition of fear extinction was facilitated by pharmacological stimulation of the IL. Together, these results were taken to imply that a memory of CS-alone exposures is stored in the IL, survives fear conditioning of the CS, and can be retrieved and strengthened during extinction or re-extinction of that CS (regardless of whether the extinction is first- or second-learned). Hence, under these circumstances, the initial extinction of fear to the CS can be facilitated by pharmacological stimulation of the IL, and re-extinction of fear to the CS can occur in the absence of a functioning BLA.

Know safety, no fear

“…The neural circuitry and molecular mechanisms involved in fear extinction have already been reviewed in depth in several recent reviews (e.g. 10,81,[91][92][93] ). Here we will provide a brief summary, highlighting findings within the amygdalo-cortico-hippocampal circuit.…”

Editorial: the psychopharmacology of extinction—from theory to therapy

“…But how does relearning extinction differ from extinguishing fear for the first time? Westbrook and colleagues (Lingawi et al 2019) review key neural and pharmacological differences between extinction and re-extinction that have major implications for repeated rounds of prolonged exposure therapy.…”

Cortical-subcortical structural connections support transcranial magnetic stimulation engagement of the amygdala

“…It is possible, however, that enhancing amygdala activity may prove beneficial in some contexts. Increases in amygdala neuronal activity are required, for example, for the extinction of conditioned fear ( 4 , 48 , 49 ). Although TMS pulses reduced amygdala activity in most participants, about one quarter of the study sample did experience a sizeable positive amygdala evoked response, providing evidence for variability in neural responses that could potentially extend to variability in TMS treatment responses.…”