G9a influences neuronal subtype specification in striatum

Nature Neuroscience (Impact Factor: 16.1). 03/2014; 17(4). DOI: 10.1038/nn.3670
Source: PubMed


Cocaine-mediated repression of the histone methyltransferase (HMT) G9a has recently been implicated in transcriptional, morphological and behavioral responses to chronic cocaine administration. Here, using a ribosomal affinity purification approach, we found that G9a repression by cocaine occurred in both Drd1-expressing (striatonigral) and Drd2-expressing (striatopallidal) medium spiny neurons. Conditional knockout and overexpression of G9a within these distinct cell types, however, revealed divergent behavioral phenotypes in response to repeated cocaine treatment. Our studies further indicated that such developmental deletion of G9a selectively in Drd2 neurons resulted in the unsilencing of transcriptional programs normally specific to striatonigral neurons and in the acquisition of Drd1-associated projection and electrophysiological properties. This partial striatopallidal to striatonigral 'switching' phenotype in mice indicates a new role for G9a in contributing to neuronal subtype identity and suggests a critical function for cell type-specific histone methylation patterns in the regulation of behavioral responses to environmental stimuli.

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Available from: Melanie J von Schimmelmann, Nov 05, 2014
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    • "Considering that there are two main types of MSNs: those expressing D1-like receptors and those that express D2-like dopamine receptors (Sesack et al., 1994; Hara and Pickel, 2005; D'Ascenzo et al., 2009; Podda et al., 2010), and that these cell subtypes show different responses to cocaine exposure (Lobo et al., 2010; Maze et al., 2014), it would be of interest to establish whether these two neuronal subtypes differentially express D-serine machin- ery. As in other brain areas, the presence of D-serine in the NAc is related to its ability to act as NMDAR co-agonist at synaptic level. "
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