Postnatal development of neurotransmitter systems and their relevance to extinction of conditioned fear

- Relapse-resistant extinction in juvenile rodents may be due to high NMDA-NR2B, mGlu5, and/or nicotinic receptor signaling in the amygdala.
- Extinction deficit in adolescence may be due to low NMDA-NR2B, and/or low D2R relative to D1R signaling in the PFC.
- High corticotropin releasing factor, and/or reduced cannabinoid signaling in the amygdala may be related to impaired extinction in adolescence.
- Changes in the localization of oxytocin receptors in the amygdala may explain transition from effective to ineffective extinction across development.

Remembering and forgetting are fundamental features of an organism. Extinction is a type of forgetting where there is a decrease in the significance and/or the meaning of an associative memory when elements of that memory no longer predict one another. The neural mechanisms underlying extinction of fear memories have been extensively studied in the laboratory because extinction processes are clinically relevant to exposure therapies that treat anxiety disorders. However, only in the last decade have we begun to unveil the similarities and differences in plasticity underlying extinction across development. So far it is clear that extinction is a developmentally dissociated process in behavior and in pharmacology, however there are many large gaps in the literature in understanding how the developmental trajectory of different neurotransmitters contribute to changes in the nature of extinction across development. We attempt to address these gaps in the present review. Major neurotransmitter systems including the glutamatergic and GABAergic systems, the monoamines, the endogenous opioid and cannabinoid systems, acetylcholines, and neuropeptides such as oxytocin have all been identified to play some role in extinction of fear memories and have been covered in this review. We hope to facilitate more research into mechanisms of extinction at different stages of life, especially noting that mental disorders are increasingly classified as neurodevelopmental disorders.