(provided by candidate): Neuropathology of hippocampal interneurons due to decreased response can result in run-away activity causing epilepsy, while increased activity eliminates the hippocampal theta rhythm, which is absent in Alzheimer's patients. Therefore, understanding how interneurons activity levels maintain the appropriate feedback control of pyramidal cells is extremely important. Long-term potentiation and depression (LTP/LTD) are activity-dependent synaptic changes that alter neuronal activity, and are mediated by AMPA glutamate receptor movement into or out of a synapse. Surprisingly, despite their obvious importance little is known about the LTD induction mechanism within hippocampal interneurons. This application will test the following aims using whole cell electrophysiology, molecular biology (RT-PCR) and pharmacology: (1) determine the interneuron subclass displaying LTD and whether it occurs in cells lacking GluR2 AMPA receptor subunits, (2) determine the signaling cascade required to trigger this LTD, and (3), establish whether the postsynaptic or presynaptic domain is the site of LTD modification. Collectively, understanding the mechanisms mediating interneuron LTD will be important to correct for interneuron dysfunction in the hippocampus.
|Edwards, Jeffrey G; Gibson, Helen E; Jensen, Tyron et al. (2012) A novel non-CB1/TRPV1 endocannabinoid-mediated mechanism depresses excitatory synapses on hippocampal CA1 interneurons. Hippocampus 22:209-21|