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Dopamine and the Neostriatum A major target for midbrain dopaminergic neurons is the neostriatum (Figure 2). Compared to other brain regions, the neostriatum is remarkably homogeneous. About 95% of all neostriatal neurons have a similar morphology and are referred to as medium-sized spiny neurons. They are the only known projection neurons in the(More)
Dendritic spines receive the vast majority of excitatory synaptic contacts in the mammalian brain and are presumed to contain machinery for the integration of various signal transduction pathways. Protein phosphatase 1 (PP1) is greatly enriched in dendritic spines and has been implicated in both the regulation of ionic conductances and long-term synaptic(More)
The activation of cAMP-dependent protein kinase regulates the physiological activity of AMPA-type glutamate receptors. In this study, phosphorylation of the AMPA receptor subunit GluR1 at Ser(845) was increased in neostriatal slices by activation of D1-type dopamine receptors and by inhibitors of protein phosphatase 1/protein phosphatase 2A. In contrast,(More)
Spinophilin, a protein that interacts with actin and protein phosphatase-1, is highly enriched in dendritic spines. Here, through the use of spinophilin knockout mice, we provide evidence that spinophilin modulates both glutamatergic synaptic transmission and dendritic morphology. The ability of protein phosphatase-1 to regulate the activity of(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)
Estrogen (E) treatment induces axospinous synapses in rat hippocampus in vivo and in cultured hippocampal neurons in vitro. To better explore the molecular mechanisms underlying this phenomenon, we have established a mouse model for E action in the hippocampus by using Golgi impregnation to examine hippocampal dendritic spine morphology,(More)
Spinophilin is a protein phosphatase 1 (PP1)- and actin-binding protein that modulates excitatory synaptic transmission and dendritic spine morphology. We report that spinophilin is phosphorylated in vitro by protein kinase A (PKA). Phosphorylation of spinophilin was stimulated by treatment of neostriatal neurons with a dopamine D1 receptor agonist or with(More)
Prefrontal cortical functioning depends on dopaminergic neurotransmission, which in turn depends on a complex signal transduction pathway including protein phosphatase-1 (PP1). Targeted localization of PP1 by the scaffolding proteins, spinophilin and neurabin, is critical for dopaminergic modulation of glutamate neurotransmission. In this study, we report(More)
The noradrenergic system in the prefrontal cortex (PFC) is involved in many physiological and psychological processes, including working memory and mood control. To understand the functions of the noradrenergic system, we examined the regulation of NMDA receptors (NMDARs), key players in cognition and emotion, by alpha1- and alpha2-adrenergic receptors(More)
The axonal shafts of neurons contain bundled microtubules, whereas extending growth cones contain unbundled microtubule filaments, suggesting that localized activation of microtubule-associated proteins (MAP) at the transition zone may bundle these filaments during axonal growth. Dephosphorylation is thought to lead to MAP activation, but specific molecular(More)