Anxiety disorders that develop in adolescence represent a significant burden and are particularly challenging to treat, due in no small part to the high occurrence of relapse in this age group following exposure therapy. This pattern of persistent fear is preserved across species; relative to those younger and older, adolescents consistently show poorer extinction, a key process underpinning exposure therapy. This suggests that the neural processes underlying fear extinction are temporarily but profoundly compromised during adolescence. The formation, retrieval, and modification of fear- and extinction-associated memories are regulated by a forebrain network consisting of the prefrontal cortex (PFC), the amygdala, and the hippocampus. These regions undergo robust maturational changes in early life, with unique alterations in structure and function occurring throughout adolescence. In this review, we focus primarily on two of these regions—the PFC and the amygdala—and discuss how changes in plasticity, synaptic transmission, inhibition/excitation, and connectivity (including modulation by hippocampal afferents to the PFC) may contribute to transient deficits in extinction retention. We end with a brief consideration of how exposure to stress during this adolescent window of vulnerability can permanently disrupt neurodevelopment, leading to lasting impairments in pathways of emotional regulation.

Perineuronal nets (PNNs) are extracellular matrix structures that preferentially surround mature GABAergic neurons that express the calcium-binding protein parvalbumin (PV). It has been suggested that aberrant PNN formation in humans may contribute to psychological disorders, many of which emerge during childhood and adolescence. The present experiment investigated the normative developmental trajectory of PNN formation in the medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) in juvenile (P24), adolescent (P35-36), and adult (∼P70) rats. Dual-immunofluorescence staining revealed that there was a marked increase in the number of PNNs in both the prelimbic and infralimbic regions of the mPFC across the transition from the juvenile to adolescent period. Although there were no differences in the number of PV neurons across age groups, adolescent and adult rats had more PNNs surrounding PV neurons than juveniles. In contrast to the mPFC, juvenile and adolescent rats had similar total numbers of PNNs in the BLA, and total numbers of PNNs were even higher in adults in this region. In the BLA, adults had more PNNs around non-PV cells whereas the number of PV cells with PNNs did not differ across ages. However, expression patterns differed within subregions of the BLA such that adults had the most PNNs around both PV and non-PV cells in the lateral nucleus, with no age differences observed in the basal nucleus. These findings demonstrate that the juvenile to adolescent developmental period is an important time for the formation of prefrontal PNNs and the maturation of PV inhibitory neurons. (PsycINFO Database Record

Adolescent rats exhibit impaired extinction retention compared to pre-adolescent and adult rats. A single nonreinforced exposure to the conditioned stimulus (CS; a retrieval trial) given shortly before extinction has been shown in some circumstances to reduce the recovery of fear after extinction in adult animals. This study investigated whether a retrieval–extinction procedure would reduce the recovery of extinguished fear in adolescent rats. Furthermore, the effect of the retrieval–extinction sequence on fear recovery was examined by presenting the retrieval trial following extinction to some animals. In Experiment 1 adolescent rats received one nonreinforced CS presentation (a retrieval trial) or equivalent context exposure (no retrieval) 10 min before fear extinction. A retrieval trial shortly before extinction reduced overall levels of fear in both test contexts (i.e., it improved extinction retention and reduced renewal). In Experiment 2 a weakening of renewal was observed with a retrieval–extinction manipulation, regardless of whether the retrieval trial occurred in the training or extinction context. A key result was that a retrieval trial 10 min, but not 6 h,afterextinction led to reduced overall levels of fear similar to that observed if the retrieval trial was given before extinction (Experiments 3 and 4), inconsistent with the current interpretation of the reduction in relapse being due to a disruption of reconsolidation. Together, these findings show that the impaired extinction retention observed in adolescents can be ameliorated by a very simple behavioral manipulation, but also raise some questions about the mechanisms underlying the retrieval–extinction effect.