Synaptic plasticity induced by convergent dopaminergic and glutamatergic striatal afferents is a substrate for emotional memory in the brain. We have found that activation of both NMDA-type glutamate receptors and dopamine D1 receptors induces phosphorylation of neuronal nitric oxide synthase (nNOS) at its putative activation site, Ser 1412, and increases accumulation of cyclic GMP (cGMP). The mechanism of D1R activation of the nNOS pathway will be investigated, focusing on the role of Akt in phosphorylation of nNOS. Ramifications for D1R/NMDAR activation of CREB and ERK, proteins important for long-term synaptic plasticity, will be investigated and the role of cGMP in activity changes determined. Assays for changes in surface expression of the AMPA receptor subunit GluR1 in response to D1R and NMDAR-induced cGMP accumulation will be performed. Patch clamp recordings will be performed on cultured striatal neurons, and the effects of D1 R/NMDAR convergence at nNOS in potentiation of mEPSCs will be determined. We hypothesize that activation of nNOS by D1 R/NMDAR stimulation is important for rapidly potentiating synapses by increasing the rate of trafficking of calcium-permeable AMPA receptors to the membrane.
| Tukey, David S; Ziff, Edward B (2013) Ca2+-permeable AMPA (?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors and dopamine D1 receptors regulate GluA1 trafficking in striatal neurons. J Biol Chem 288:35297-306 |
| Tukey, David S; Lee, Michelle; Xu, Duo et al. (2013) Differential effects of natural rewards and pain on vesicular glutamate transporter expression in the nucleus accumbens. Mol Brain 6:32 |
| Tukey, David S; Ferreira, Jainne M; Antoine, Shannon O et al. (2013) Sucrose ingestion induces rapid AMPA receptor trafficking. J Neurosci 33:6123-32 |
| Rameau, Gerald A; Tukey, David S; Garcin-Hosfield, Elsa D et al. (2007) Biphasic coupling of neuronal nitric oxide synthase phosphorylation to the NMDA receptor regulates AMPA receptor trafficking and neuronal cell death. J Neurosci 27:3445-55 |
