Lack of experience‐dependent intrinsic plasticity in the adolescent infralimbic medial prefrontal cortex

Abstract

Fear extinction, an inhibitory learning that suppresses a previously learned fear memory, is diminished during adolescence. Earlier studies have shown that this suppressed fear extinction during adolescence involves an altered glutamatergic plasticity in infralimbic medial prefrontal cortical (IL‐mPFC) pyramidal neurons. However, it is unclear whether the excitability of IL‐mPFC pyramidal neurons plays a role in this development‐dependent suppression of fear extinction. Therefore, we examined whether fear conditioning and extinction affect the active and passive membrane properties of IL‐mPFC layer 5 pyramidal neurons in preadolescent, adolescent and adult mice. Both preadolescent and adult mice exhibited a bidirectional modulation of the excitability of IL‐mPFC layer 5 pyramidal neurons following fear conditioning and extinction, i.e., fear conditioning reduced membrane excitability, whereas fear extinction reversed this effect. However, the fear conditioning‐induced suppression of excitability was not reversed in adolescent mice following fear extinction training. Neither fear conditioning nor extinction affected GABAergic transmission in IL‐mPFC layer 5 pyramidal neurons, suggesting that GABAergic transmission did not play a role in experience‐dependent modulation of neuronal excitability. Our results suggest that the extinction‐specific modulation of excitability is impaired during adolescence.

Development-Dependent Plasticity in Vasoactive Intestinal Polypeptide Neurons in the Infralimbic Cortex

“…Given that we observed far fewer evoked action potentials in VIPINs ( Fig. 1 B , C ) than in other IL-mPFC neurons ( Koppensteiner et al. 2019a ; Koppensteiner et al.…”

“…Our earlier studies have demonstrated an attenuation of both glutamatergic and intrinsic plasticity in the IL-mPFC pyramidal neurons during adolescence ( Pattwell et al. 2012 ; Koppensteiner et al. 2019b ).…”

“…Female and male preadolescent (postnatal day 24, P24), adolescent (P29), and adult mice (>P60) were used in this study ( Koppensteiner et al. 2019b ; Koppensteiner et al.…”

“…This diminished threat extinction during adolescence is associated with an altered synaptic and intrinsic plasticity in the infralimbic medial prefrontal cortex (IL-mPFC) pyramidal neurons ( Pattwell et al. 2012 ; Koppensteiner et al. 2019a ).…”

Fear Learning Enhances Prefrontal Cortical Suppression of Auditory Thalamic Inputs to the Amygdala in Adults, but Not Adolescents

“…While the PL is believed to be involved in the attention directed at a given stimulus during uncertainty, changes in IL activity direct the context sensitivity of a response, perhaps guided by the strongest CS association (e.g., renewal, and discrimination of over-and under-trained cues) [6,20,23,24]. Many developmental differences are seen between adults and adolescents with regard to IL-dependent behavior [6,25], commonly measured as reduced flexibility in behavioral responding during tasks that require suppression of a learned response, such as fear extinction, and are attributed to the immaturity of IL projections [6,[25][26][27]. IL inputs to the BLA are potentiated following initial fear learning and IL-BLA excitability is increased following extinction in adults [28,29], highlighting that IL inputs can change in many conditions where behavioral flexibility is guided by context or competing environmental cues, whether or not suppression of a behavioral response is required [30].…”