Neuroscience
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NMDA receptors are found in neurons both at synapses and in extrasynaptic locations. Extrasynaptic locations are poorly characterized. Here we used preembedding immunoperoxidase and postembedding immunogold electron microscopy and fluorescence light microscopy to characterize extrasynaptic NMDA receptor locations in dissociated hippocampal neurons in vitro and in the adult and postnatal hippocampus in vivo. ⋯ This difference probably indicates that many sites of extrasynaptic NMDA receptors in early postnatal ages represent synapse formation or possibly sites for synapse elimination. At all ages, as suggested in both in vivo and in vitro studies, extrasynaptic NMDA receptors on dendrites or the sides of spines may form complexes with other proteins, in many cases, at stable associations with adjacent cell processes. These associations may facilitate unique functions for extrasynaptic NMDA receptors.
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The perifornical-lateral hypothalamic area (PF-LHA) plays a central role in the regulation of behavioral arousal. The PF-LHA contains several neuronal types including wake-active hypocretin (HCRT) neurons that have been implicated in the promotion and/or maintenance of behavioral arousal. Adenosine is an endogenous sleep factor and recent evidence suggests that activation and blockade of adenosine A(1) receptors within the PF-LHA promote and suppress sleep, respectively. ⋯ CPA significantly suppressed the sleep-wake discharge activity of PF-LHA neurons. Doses of CPA (50 muM) and CPDX (50 muM) that suppressed and induced arousal, respectively, in our earlier study [Alam MN, Kumar S, Rai S, Methippara M, Szymusiak R, McGinty D (2009) Brain Res 1304:96-104], significantly suppressed and increased Fos-IR in HCRT and non-HCRT neurons. These findings suggest that wake-promoting PF-LHA system is subject to increased endogenous adenosinergic inhibition and that adenosine acting via A(1) receptors, in part, inhibits HCRT neurons to promote sleep.
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Extraversion/introversion is a basic dimension of personality that describes individual differences in social behavior and sensory sensitivity. Previous neuroimaging research exclusively relied on self reports for assessing personality traits. In recent years, implicit measures of personality have been developed that aim at assessing the implicit self-concept of personality and complement self report instruments which are thought to measure aspects of the explicit self-concept of personality. ⋯ Neither NEO-FFI extraversion nor IAT effect were significantly related to brain response to masked neutral faces (compared to the no face condition). Taken together, a specific heightened responsivity of the fronto-striatal-thalamic circuit to facial emotions which are arousing stimuli might underlie introverts' preference for avoiding social interactions. Research on the neurobiology of extraversion could benefit from the application of implicit in addition to explicit measurement instruments when automatic neural responses are investigated.
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It has been reported that N-methyl-D-aspartate receptor (NMDAR)-triggered neurotoxicity is related to excessive Ca(2+) loading and an increase in nitric oxide (NO) concentration. However, the molecular mechanisms that underlie these events are not completely understood. NMDARs and neuronal NO synthase each binds to the scaffolding protein postsynaptic density (PSD)-93 through its PDZ domains. ⋯ PSD-93 deficiency reduced the amount of NMDAR subunits NR2A and NR2B in synaptosomal fractions from the cortical neurons and significantly prevented NMDA-stimulated increases in cyclic guanosine 3',5'-monophosphate and Ca(2+) loading in the cortical neurons. These findings indicate that PSD-93 deficiency could block NMDAR-triggered neurotoxicity by disrupting the NMDAR-Ca(2+)-NO signaling pathway and reducing expression of synaptic NR2A and NR2B. Since NMDARs, Ca(2+), and NO play a critical role during the development of brain trauma, seizures, and ischemia, the present work suggests that PSD-93 might contribute to molecular mechanisms of neuronal damage in these brain disorders.
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Platelet-activating factor (PAF) is an important inflammatory lipid mediator affecting neural plasticity. In the present study, we demonstrated how PAF affects synaptic efficacy through activation of protein kinases in the rat hippocampal CA1 region. In cultured hippocampal neurons, 10 to 1000 nM PAF stimulated autophosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) and phosphorylation of synapsin I and myristoylated alanine-rich protein kinase C substrate (MARCKS). ⋯ Phosphorylation of MARCKS (Ser-152/156) and NMDA receptor subunit 1 (NR1) (Ser-896) as PKCalpha substrates also significantly increased after 10 min but had not further increased by 50 min in the CA1 region. Increased of fEPSPs induced by PAF treatment completely and/or partly inhibited by KN93 and/or U0126 treatment. These results suggest that PAF induces synaptic facilitation through activation of CaMKII, PKC and ERK in the hippocampal CA1 region.