Homer1a drives homeostatic scaling-down of excitatory synapses during sleep

Diering, Graham H.; Nirujogi, Raja Sekhar; Roth, Richard H.; Worley, Paul F.; Pandey, Akhilesh; Huganir, Richard L.

doi:10.1126/science.aai8355

Cited by 409 publications

(477 citation statements)

References 35 publications

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“…Synaptic scaling is also observed in vivo (Desai et al, 2002; Diering et al, 2017; Hengen et al, 2016; Lee and Whitt, 2015). A wide range of intracellular and extracellular molecules and signaling pathways regulate homeostatic scaling.…”

Section: Introductionmentioning

confidence: 88%

Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate Sema3F-Dependent Homeostatic Scaling in Cortical Neurons

Wang

Chiu

Koropouli

et al. 2017

Neuron

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SUMMARY Regulation of AMPA-type glutamate receptor (AMPAR) number at synapses is a major mechanism for controlling synaptic strength during homeostatic scaling in response to global changes in neural activity. We show that the secreted guidance cue semaphorin 3F (Sema3F) and its neuropilin-2 (Npn-2)/plexinA3 (PlexA3) holoreceptor mediate homeostatic plasticity in cortical neurons. Sema3F-Npn-2/PlexA3 signaling is essential for cell surface AMPAR homeostatic downscaling in response to an increase in neuronal activity, Npn-2 associates with AMPARs, and Sema3F regulates this interaction. Therefore, Sema3F-Npn-2/PlexA3 signaling controls both synapse development and synaptic plasticity.

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Section: Introductionmentioning

confidence: 88%

Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate Sema3F-Dependent Homeostatic Scaling in Cortical Neurons

Wang

Chiu

Koropouli

et al. 2017

Neuron

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“…A recent study showed that the removal of AMPA receptors in mouse forebrain during sleep depends on the disruption of group I mGluR signaling scaffolds by Homer1a [112]. It is proposed that this mechanism of homeostatic scaling is coordinated by circadian patterns of noradrenaline and adenosine during the accumulation of sleep need, and which promotes synaptic remodeling for the facilitation of memory consolidation [112]. …”

Section: Functional Plasticitymentioning

confidence: 99%

“…The role of Homer1a in homeostatic synaptic scaling extends to the regulation of AMPA receptors during sleep [112-114]. A recent study showed that the removal of AMPA receptors in mouse forebrain during sleep depends on the disruption of group I mGluR signaling scaffolds by Homer1a [112].…”

Section: Functional Plasticitymentioning

confidence: 99%

Regulation and Function of Activity-Dependent Homer in Synaptic Plasticity

et al. 2019

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Alterations in synaptic signaling and plasticity occur during the refinement of neural circuits over the course of development and the adult processes of learning and memory. Synaptic plasticity requires the rearrangement of protein complexes in the postsynaptic density (PSD), trafficking of receptors and ion channels and the synthesis of new proteins. Activity-induced short Homer proteins, Homer1a and Ania-3, are recruited to active excitatory synapses, where they act as dominant negative regulators of constitutively expressed, longer Homer isoforms. The expression of Homer1a and Ania-3 initiates critical processes of PSD remodeling, the modulation of glutamate receptor-mediated functions, and the regulation of calcium signaling. Together, available data support the view that Homer1a and Ania-3 are responsible for the selective, transient destabilization of postsynaptic signaling complexes to facilitate plasticity of the excitatory synapse. The interruption of activity-dependent Homer proteins disrupts disease-relevant processes and leads to memory impairments, reflecting their likely contribution to neurological disorders.

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“…A recent neurochemical study examining sleep-loss-induced HOMER1a association with synaptic PSD95 protein (14), showed that beta- and alpha-receptor antagonists could prevent the normal NE-mediated inhibition of HOMER1a-PSD95 binding. This provide a correlation between waking induced NE tone and the interference with synaptic PSD95-Homer1a binding.…”

Section: Mechanisms Controlling the Sleep Homeostatic Responsementioning

confidence: 99%

The adenosine-mediated, neuronal-glial, homeostatic sleep response

Greene¹,

Bjorness

Suzuki

2017

Current Opinion in Neurobiology

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Slow wave activity (SWA) during slow wave sleep (SWS) is the best indicator of the sleep homeostasis. The intensity of the SWA observed during SWS that follows prolonged waking is directly correlated with the duration of prior waking and its intensity decays during SWS suggesting a buildup and a resolution of sleep need. This sleep-homeostasis related SWA results from a buildup and decay of extracellular adenosine that acts at neuronal adenosine A1 receptors to facilitate SWA and is metabolized by adenosine kinase found in glia. This local neuronal-glial circuit for homeostatic SWA is primarily under the requisite control of two genes, the Adora1 and Adk, encoding the responsible adenosine receptor and adenosine’s highest affinity metabolizing enzyme.

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Homer1a drives homeostatic scaling-down of excitatory synapses during sleep

Cited by 409 publications

References 35 publications

Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate Sema3F-Dependent Homeostatic Scaling in Cortical Neurons

Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate Sema3F-Dependent Homeostatic Scaling in Cortical Neurons

Regulation and Function of Activity-Dependent Homer in Synaptic Plasticity

The adenosine-mediated, neuronal-glial, homeostatic sleep response

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