Angus C. Nairn

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Proc. Natl. Acad. Sci. U.S.A. 92, 2682 (1995). 29. A. Nishi, G. L. Snyder, P. Greengard, J. Neurosci. 17, 8147 (1997). 30. G. L. Snyder, A. A. Fienberg, R. L. Huganir, P. Greengard, J. Neurosci. 18, 10297 (1998) 31. P. Svenningsson et al., Neurosci. 84, 223 (1998). 32. A. Nishi, G. L. Snyder, A. C. Nairn, P. Greengard, J. Neurochem. 72, 2015 (1999). 33. P.(More)
Amyloid-beta peptide is elevated in the brains of patients with Alzheimer disease and is believed to be causative in the disease process. Amyloid-beta reduces glutamatergic transmission and inhibits synaptic plasticity, although the underlying mechanisms are unknown. We found that application of amyloid-beta promoted endocytosis of NMDA receptors in(More)
striatum, and therefore function to integrate all input to Introduction this brain region. DARPP-32 is expressed in very high Of the many slow-acting neurotransmitters utilized by concentration (z50 mM) in virtually all medium spiny the mammalian central nervous system, dopamine has neurons (Ouimet et al., 1984, 1998) (Figure 2). Medium received by far the(More)
In rat neostriatal neurons, D1 dopamine receptors regulate the activity of cyclic AMP-dependent protein kinase (PKA) and protein phosphatase 1 (PP1). The influence of these signaling elements on high voltage-activated (HVA) calcium currents was studied using whole-cell voltage-clamp techniques. The application of D1 agonists or cyclic AMP analogs reversibly(More)
Many drugs of abuse exert their addictive effects by increasing extracellular dopamine in the nucleus accumbens, where they likely alter the plasticity of corticostriatal glutamatergic transmission. This mechanism implies key molecular alterations in neurons in which both dopamine and glutamate inputs are activated. Extracellular signal-regulated kinase(More)
Dopamine- and cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32), was identified initially as a major target for dopamine and protein kinase A (PKA) in striatum. However, recent advances now indicate that regulation of the state of DARPP-32 phosphorylation provides a mechanism for integrating information arriving at dopaminoceptive neurons, in multiple(More)
Cocaine enhances dopamine-mediated neurotransmission by blocking dopamine re-uptake at axon terminals. Most dopamine-containing nerve terminals innervate medium spiny neurons in the striatum of the brain. Cocaine addiction is thought to stem, in part, from neural adaptations that act to maintain equilibrium by countering the effects of repeated drug(More)
The physiological state of the cell is controlled by signal transduction mechanisms which regulate the balance between protein kinase and protein phosphatase activities. Here we report that a single protein can, depending on which particular amino-acid residue is phosphorylated, function either as a kinase or phosphatase inhibitor. DARPP-32 (dopamine and(More)
Psychostimulant-induced alteration of dendritic spines on dopaminoceptive neurons in nucleus accumbens (NAcc) has been hypothesized as an adaptive neuronal response that is linked to long-lasting addictive behaviors. NAcc is largely composed of two distinct subpopulations of medium-sized spiny neurons expressing high levels of either dopamine D1 or D2(More)
Modulation of AMPA-type glutamate channels is important for synaptic plasticity. Here we provide physiological evidence that the activity of AMPA channels is regulated by protein phosphatase 1 (PP-1) in neostriatal neurons and identify two distinct molecular mechanisms of this regulation. One mechanism involves control of PP-1 catalytic activity by(More)