Synaptic plasticity in hippocampal interneurons: cellular mechanisms. (360G-Wellcome-078117_Z_05_Z)

We have recently found that NMDA receptor-dependent long-term potentiation (LTP) occurs in about half of GABAergic feed-forward inhibitory interneurons in stratum radiatum of the hippocampus. This is only detected if interneurons are recorded in perforated-patch mode, and is not seen if whole-cell pipettes are used, possibly explaining why the phenomenon has not previously been reported. LTP in aspiny interneurons has extensive repercussions for the interaction between memory encoding and information processing in the corticalmicrocircuitry. However, the focus of this application is the underlying cellular mechanisms. Are postsynaptic action potentials required for LTP induction? Can LTP-competent interneurons be identified electrophysiologicallyor anatomically? Can interneurons switch from LTP-incompetence to LTP-competence? What is the role of tyrosine phosphorylation of NMDA receptors? What is the induction cascade downstream of NMDA receptors? How do sub-cellular Ca2+ microdomains relate to pathway-specific LTP in aspiny cells?Do interneurons exhibit NMDA receptor-dependent long-term depression (LTD)? What are the roles of NR2A- and NR2B-containing NMDA receptors, Ca2+/calmodulin kinases, and calcineurin in LTP (and LTD) in interneurons?