The missing link: Opioid modulation of AMPA receptors

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Major Depressive Disorder is a leading cause of global disability; however, current standard treatments are ineffective. The Lambert lab discovered that in the mouse hippocampus the pro-cognitive atypical antidepressant tianeptine employs a novel receptor crosstalk, activating delta-opioid receptors (DORs), increasing excitatory glutamatergic neurotransmission via calcium-permeable AMPA receptors (CP-AMPARs). However, the underlying biochemical signalling pathway is yet to be elucidated. Preliminary evidence implicates an involvement of CAMKII and PKA with a putative upstream involvement of the MAPK signalling pathway.This project will investigate the interactions between opioid and CP-AMPA receptors at the molecular, cellular and systems level using biochemical and electrophysiological techniques to gain a deeper understanding into this receptor crosstalk. Furthermore, this crosstalk has been implicated in synaptic plasticity, Events that lead to the release of endogenous opioids, such as mild stress or physical exercise, can enhance long-term potentiation (LTP) of synaptic strength. Therefore, the potential relationship between opioid receptors, CP-AMPARs and synaptic plasticity will be investigated.