Activity-dependent regulation of inhibitory synapse development by Npas4

By Yingxi Lin, Brenda L. Bloodgood, Jessica L. Hauser, A. Lapan, A. Koon, Tae-Kyung Kim, Linda S. Hu, Athar N. Malik, Michael E. Greenberg. Nature, 2008

625 citations recorded by the source corpus.

Neuronal activity regulates the development and maturation of excitatory and inhibitory synapses in the mammalian brain. Several recent studies have identified signalling networks within neurons that control excitatory synapse development. However, less is known about the molecular mechanisms that regulate the activity-dependent development of GABA (γ-aminobutyric acid)-releasing inhibitory synapses. Here we report the identification of a transcription factor, Npas4, that plays a role in the development of inhibitory synapses by regulating the expression of activity-dependent genes, which in turn control the number of GABA-releasing synapses that form on excitatory neurons. These findings demonstrate that the activity-dependent gene program regulates inhibitory synapse development, and suggest a new role for this program in controlling the homeostatic balance between synaptic excitation and inhibition.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/992aeff798e47c8165502bc72edac8d1e72b5e47

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Citations in the corpus

Wiring and Molecular Features of Prefrontal Ensembles Representing Distinct Experiences (2016, neutral): “Indeed, no difference was observed when we examined Npas4 expression in whole-tissue lysates from cocaineand shock-labeled mPFC (Figure 5E), indicating that exposure to cocaine did not lead to an overall long-term increase of Npas4 expression in mPFC.”
Krüppel-Like Factor 9 Is Necessary for Late-Phase Neuronal Maturation in the Developing Dentate Gyrus and during Adult Hippocampal Neurogenesis (2009, result): “Our results, together with a recent study that showed upregulation of Klf-9 expression after membrane depolarization of cultured cortical neurons (Lin et al., 2008), indicate that Klf-9 expression is induced by neuronal activity both in vitro and in vivo.”
Mapping of brain activity by automated volume analysis of immediate early genes (2016, positive): “Npas4 showed modest up-regulation of expression 30 min and 1 hr after stimulation (2.2 and 2.1 respectively) (Figure 2A and B), well within the induction window reported in vivo for the cortex (Lin et al., 2008; Spiegel et al., 2014).”
Editing DNA methylation in the mammalian genome (2016, neutral): “Importantly, the same group of dCas9-Tet1/gRNAs did not induce Npas4 expression (Figure S4F), another neuronal activity-inducible gene (Lin et al., 2008).”
The Angelman Syndrome-associated ubiquitin ligase Ube3A regulates synapse development by ubiquitinating Arc (2010, positive): “…Ube3A knockout brains, suggesting that the increase in Arc in Ube3A knockout mouse brain is not the 708 Cell 140, 704–716, March 5, 2010 ª2010 Elsevier Inc. result of an overall increase in the activity-dependent gene response (Figure 3F and data not shown) (Zhou et al., 2006; Lin et al., 2008).”
REM sleep and dreaming: towards a theory of protoconsciousness (2009, background): “A paradoxical improvement in mood is observed in depressed patients after one night of REM sleep deprivatio”
From synapse to nucleus: calcium-dependent gene transcription in the control of synapse development and function. (2008, background): “A similar process of synapse elimination occurs in the CNS (e.g., the retinogeniculate synapse, the synapse made by retinal ganglion neurons onto thalamic neurons, and the climbing fiber/Purkinje cell synapse in the cerebellum) (Chen and Regehr, 2000; Nishiyama and Linden, 2004).”
Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway (2013, background): “However, Npas4, an important transcriptional component in hippocampal function and a key regulator of activity-induced Bdnf expression (Lin et al., 2008; Ramamoorthi et al., 2011), was not increased in the exercise regimen used here (Figures 1D and 1E).”
Widespread transcription at neuronal activity-regulated enhancers (2010, neutral): “CREB, SRF, and NPAS4 are known activity-regulated TFs that play an important role in various aspects of brain development including neuronal survival, synapse development and synaptic plasticity15,16.”