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  • 1
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    Activity-dependent regulation of inhibitory synapse development by Npas4 (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-09-26
    Description: 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 (gamma-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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637532/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637532/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Yingxi -- Bloodgood, Brenda L -- Hauser, Jessica L -- Lapan, Ariya D -- Koon, Alex C -- Kim, Tae-Kyung -- Hu, Linda S -- Malik, Athar N -- Greenberg, Michael E -- HD18655/HD/NICHD NIH HHS/ -- NS27572/NS/NINDS NIH HHS/ -- NS48276/NS/NINDS NIH HHS/ -- P01 NS047572/NS/NINDS NIH HHS/ -- P01 NS047572-01A10001/NS/NINDS NIH HHS/ -- P01 NS047572-020001/NS/NINDS NIH HHS/ -- P01 NS047572-030001/NS/NINDS NIH HHS/ -- P01 NS047572-040001/NS/NINDS NIH HHS/ -- P01 NS047572-050001/NS/NINDS NIH HHS/ -- R01 MH091220/MH/NIMH NIH HHS/ -- R01 NS048276/NS/NINDS NIH HHS/ -- R01 NS048276-01/NS/NINDS NIH HHS/ -- R01 NS048276-02/NS/NINDS NIH HHS/ -- R01 NS048276-03/NS/NINDS NIH HHS/ -- R01 NS048276-04/NS/NINDS NIH HHS/ -- R01 NS048276-05/NS/NINDS NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- England -- Nature. 2008 Oct 30;455(7217):1198-204. doi: 10.1038/nature07319. Epub 2008 Sep 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉F. M. Kirby Neurobiology Center, Children's Hospital and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18815592" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism ; Brain-Derived Neurotrophic Factor/metabolism ; Cells, Cultured ; Electrophysiology ; Gene Expression Regulation ; Hippocampus/cytology ; Mice ; Neurons/metabolism ; Rats ; Synapses/*metabolism ; Transcription Factors/genetics/*metabolism ; Transfection ; gamma-Aminobutyric Acid/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number (2006)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2006-02-18
    Description: In the mammalian nervous system, neuronal activity regulates the strength and number of synapses formed. The genetic program that coordinates this process is poorly understood. We show that myocyte enhancer factor 2 (MEF2) transcription factors suppressed excitatory synapse number in a neuronal activity- and calcineurin-dependent manner as hippocampal neurons formed synapses. In response to increased neuronal activity, calcium influx into neurons induced the activation of the calcium/calmodulin-regulated phosphatase calcineurin, which dephosphorylated and activated MEF2. When activated, MEF2 promoted the transcription of a set of genes, including arc and synGAP, that restrict synapse number. These findings define an activity-dependent transcriptional program that may control synapse number during development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Flavell, Steven W -- Cowan, Christopher W -- Kim, Tae-Kyung -- Greer, Paul L -- Lin, Yingxi -- Paradis, Suzanne -- Griffith, Eric C -- Hu, Linda S -- Chen, Chinfei -- Greenberg, Michael E -- AG05870/AG/NIA NIH HHS/ -- HD18655/HD/NICHD NIH HHS/ -- NS28829/NS/NINDS NIH HHS/ -- R01 EY013613/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2006 Feb 17;311(5763):1008-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neurobiology Program, Children's Hospital, and Departments of Neurology and Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16484497" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcineurin/metabolism ; Calcium/metabolism ; Cells, Cultured ; Cytoskeletal Proteins/genetics ; Dendrites/physiology/ultrastructure ; Excitatory Postsynaptic Potentials ; GTPase-Activating Proteins/genetics ; Gene Expression Regulation ; Glutamic Acid/metabolism ; Hippocampus/cytology/*physiology ; MEF2 Transcription Factors ; Mutation ; Myogenic Regulatory Factors/genetics/*physiology ; Nerve Tissue Proteins/genetics ; Neurons/*physiology ; Oligonucleotide Array Sequence Analysis ; Phosphorylation ; RNA Interference ; Rats ; Rats, Long-Evans ; Recombinant Fusion Proteins/metabolism ; Synapses/*physiology ; Synaptic Transmission ; Transcription, Genetic ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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