Article

NMDA receptor-independent control of transcription factors and gene expression

Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, NC 27709, USA.
Neuroreport (Impact Factor: 1.64). 09/2009; 20(16):1429-33. DOI: 10.1097/WNR.0b013e3283311db6
Source: PubMed

ABSTRACT Consolidation of synaptic plasticity seems to require transcription, but how the nucleus is informed in this context remains unknown. As NMDA receptor antagonists have been shown to interfere with action potential generation, the issue of whether or not a synaptically generated signal is required for nuclear signaling is currently unresolved. Here, we show that pharmacological maintenance of action potentials during NMDA receptor blockade allows for NMDA receptor-independent transcription factor binding and arc gene expression, both of which were previously thought to be NMDA receptor dependent. These data suggest that types of signaling in the nucleus previously attributed to NMDA-receptor-dependent synapse-to-nucleus signals can be initiated in the absence of NMDA receptor-dependent synaptic plasticity.

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Available from: Eric Hudgins, Aug 29, 2015
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    • " voltage - dependent Ca 2+ channel , also regulate Arc expression ( Kakizawa et al . , 2000 ; Hashimoto et al . , 2011 ) . To our knowledge , this is the first study to suggest that the regulation of Arc expression through CB1R activity in neonatal and adult mice . Arc tran - scription is also regulated by voltage - sensitive calcium chan - nels ( Adams et al . , 2009 ) , which are negatively regulated by CB1R ( Basavarajappa and Arancio , 2008 ) . Our findings suggest that the ERK1 / 2 - pCREB - Arc pathway is involved in neuronal survival downstream of the CB1Rs in the developing brain and is compromised by ethanol treatment . It is possible that ethanol - induced suppression of the ERK1 / 2 - pCRE"
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    • "The transcription, translation, trafficking and turnover of Arc mRNA and protein are tightly regulated and vary according to cell and stimulus type. Within minutes of NMDA receptor (NMDAR) or voltage-gated calcium channel activation, a burst of Arc transcription is initiated in all principal fields of the hippocampus (Adams, Robinson, Hudgins, Wissink, & Dudek, 2009), lasting for hours in the dentate gyrus (Lyford et al., 1995), and subsiding more rapidly in pyramidal neurons (Guzowski et al., 1999). Resulting mRNA is trafficked and targeted to specific synapses in an NMDAR-dependent manner (Farris, Lewandowski, Cox, & Steward, 2014; Moga et al., 2004; Steward et al., 1998), and although it has been widely thought to target recently activated synapses, current evidence indicates that locally translated ARC preferentially accumulates at relatively less active synaptic sites (Okuno et al., 2012). "
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    • "Thus, we considered the possibility that some Ca 2+ -dependent genes regulate CF synapse elimination in the cerebellum. We focused on an immediate early gene, Arc, because its expression is tightly coupled to neural activity downstream of multiple signaling pathways (Bramham et al., 2008; Shepherd and Bear, 2011), including Ca 2+ influx through VDCCs (Adams et al., 2009). Arc messenger RNA (mRNA) is detectable in PCs in the mouse cerebellum at an early postnatal stage, and its expression increases during postnatal development (Allen Brain Atlas; http://mouse.brain-map.org). "
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