Eric Miller ’08 is currently pursuing his Ph.D. in Neuroscience at the University of Minnesota. This past August Eric published a scientific article on my thesis research.
Below is the citation and abstract:
Mol Pharmacol. 2012 Aug;82(2):333-43. Epub 2012 May 17.
Differential modulation of drug-induced structural and functional plasticity of dendritic spines.
Miller EC, Zhang L, Dummer BW, Cariveau DR, Loh H, Law PY, Liao D.
Graduate Program in Neuroscience, Department of Neuroscience, University of Minnesota Medical School, 321 Church St. SE, Minneapolis, MN 55455, USA.
Drug-induced plasticity of excitatory synapses has been proposed to be the cellular mechanism underlying the aberrant learning associated with addiction. Exposure to various drugs of abuse causes both morphological plasticity of dendritic spines and functional plasticity of excitatory synaptic transmission. Chronic activation of μ-opioid receptors (MOR) in cultured hippocampal neurons causes two forms of synaptic plasticity: loss of dendritic spines and loss of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. With use of live imaging, patch-clamp electrophysiology, and immunocytochemistry, the present study reveals that these two forms of synaptic plasticity are mediated by separate, but interactive, intracellular signaling cascades. The inhibition of Ca(2+)/calmodulin-dependent protein kinase II with 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine (KN-62) blocks MOR-mediated structural plasticity of dendritic spines, but not MOR-mediated cellular redistribution of GluR1 and GluR2 AMPA receptor subunits. In contrast, the inhibition of calcineurin with tacrolimus (FK506) blocks both cellular processes. These findings support the idea that drug-induced structural and functional plasticity of dendritic spines is mediated by divergent, but interactive, signaling pathways.