Input-Specific Metaplasticity in the Visual Cortex Requires Homer1a-Mediated mGluR5 Signaling

Chokshi, Varun; Gao, Ming; Grier, Bryce D.; Owens, Ashley; Wang, Hui; Worley, Paul F.; Lee, Hey Kyoung

doi:10.1016/j.neuron.2019.08.017

Cited by 29 publications

(38 citation statements)

References 71 publications

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“…Mechanistically, scaling up and down are not the reverse of each other, but rely on distinct molecular signaling. In V1, upscaling of mEPSCs after DE correlates with phosphorylation of GluA1 on S845, synaptic appearance of Ca 2+ -permeable AMPARs (Goel et al, 2006), and mGluR1 (Chokshi et al, 2019), while downscaling is dependent on Arc (Gao et al, 2010), mGluR5, and Homer1a (Chokshi et al, 2019). Although GluA1-S845 is necessary for upscaling, it alone is not sufficient to recapitulate multiplicative scaling (Goel et al, 2011).…”

Section: Demonstration Of Homeostatic Synaptic Plasticity In Vivomentioning

confidence: 99%

“…Consistent with this interpretation, we reported that DE-induced upscaling of mEPSCs reflects potentiation of lateral intracortical (IC) synapses, but feedforward (FF) synapses from L4 to L2/3 are immune to this type of plasticity (Petrus et al, 2015). Similarly, downscaling of mEPSCs with visual experience is also limited to IC synapses (Chokshi et al, 2019). Such input-specific synaptic scaling is observed in L5 of V1 at the level of dendritic spine plasticity.…”

Section: Demonstration Of Homeostatic Synaptic Plasticity In Vivomentioning

confidence: 99%

“…Therefore, the cortical networks can be dynamically reconfigured for processing the most relevant information in the context of overall activity in the circuit. It is of interest to note that input-specific homeostatic plasticity is more prevalent in mature cortex (Goel and Lee, 2007; Ranson et al, 2012; Petrus et al, 2015; Barnes et al, 2017; Chokshi et al, 2019).…”

Section: Different Activity Regime May Recruit Distinct Homeostatic Smentioning

confidence: 99%

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Mechanisms of Homeostatic Synaptic Plasticity in vivo

Lee

Kirkwood

2019

Front. Cell. Neurosci.

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Synapses undergo rapid activity-dependent plasticity to store information, which when left uncompensated can lead to destabilization of neural function. It has been well documented that homeostatic changes, which operate at a slower time scale, are required to maintain stability of neural networks. While there are many mechanisms that can endow homeostatic control, sliding threshold and synaptic scaling are unique in that they operate by providing homeostatic control of synaptic strength. The former mechanism operates by adjusting the threshold for synaptic plasticity, while the latter mechanism directly alters the gain of synapses. Both modes of homeostatic synaptic plasticity have been studied across various preparations from reduced in vitro systems, such as neuronal cultures, to in vivo intact circuitry. While most of the cellular and molecular mechanisms of homeostatic synaptic plasticity have been worked out using reduced preparations, there are unique challenges present in intact circuitry in vivo, which deserve further consideration. For example, in an intact circuit, neurons receive distinct set of inputs across their dendritic tree which carry unique information. Homeostatic synaptic plasticity in vivo needs to operate without compromising processing of these distinct set of inputs to preserve information processing while maintaining network stability. In this mini review, we will summarize unique features of in vivo homeostatic synaptic plasticity, and discuss how sliding threshold and synaptic scaling may act across different activity regimes to provide homeostasis.

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Section: Demonstration Of Homeostatic Synaptic Plasticity In Vivomentioning

confidence: 99%

Section: Demonstration Of Homeostatic Synaptic Plasticity In Vivomentioning

confidence: 99%

Section: Different Activity Regime May Recruit Distinct Homeostatic Smentioning

confidence: 99%

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Mechanisms of Homeostatic Synaptic Plasticity in vivo

Lee

Kirkwood

2019

Front. Cell. Neurosci.

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“…This would favor the long-term expression of the initiated plasticity. These molecular dynamics at synapses explain reported roles of mGlu5-Homer in metaplasticity (37)(38)(39). Importantly, all these studies report Homer1a as the dominant-negative IEG breaking mGlu5-Homer interaction to allow synaptic plasticity.…”

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confidence: 56%

Restoring Glutamate receptosome dynamics at synapses rescues Autism-like deficits in Shank3-deficient mice

Moutin

Sakkaki

Compan

et al. 2020

Preprint

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Shank3 monogenic mutations lead to Autism Spectrum Disorders (ASD). Shank3 is part of the glutamate receptosome that physically links ionotropic NMDA receptors to metabotropic mGlu5 receptors through interactions with scaffolding proteins PSD95-GKAP-Shank3-Homer. A main physiological function of the glutamate receptosome is to control NMDA synaptic function that is required for plasticity induction. Intact glutamate receptosome supports glutamate receptors activation and plasticity induction, while glutamate receptosome disruption blocks receptors activity, preventing the induction of subsequent plasticity. Despite possible impact on metaplasticity and cognitive behaviors, scaffold interaction dynamics and their consequences are poorly defined. Here we used mGlu5-Homer interaction as a biosensor of glutamate receptosome integrity to report changes of NMDA synaptic function. Combining BRET imaging and electrophysiology, we show that a transient neuronal depolarization inducing NMDA-dependent plasticity disrupts glutamate receptosome in a long-lasting manner at synapses and induces signaling required for the expression of the initiated neuronal plasticity such as ERK and mTOR pathways. Glutamate receptosome disruption also decreases NMDA/AMPA currents ratio, freezing the sensitivity of the synapse to subsequent changes of neuronal activity. These data show the importance of a fine-tuning of protein-protein interactions within glutamate receptosome, driven by changes of neuronal activity, to control plasticity. In a mouse model of ASD, a truncated mutant form of Shank3 prevents the integrity of the glutamate receptosome. These mice display altered plasticity, anxiety-like and stereotyped behaviors. Interestingly, repairing the integrity of glutamate receptosome and its sensitivity to the neuronal activity rescued synaptic transmission, plasticity and some behavioral traits of Shank3∆C mice. Altogether, our findings characterize mechanisms by which Shank3 mutations cause ASD and highlight scaffold dynamics as new therapeutic target.

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“…In addition to inducing Hebbian plasticity, alterations in visual experience produce homeostatic plasticity of excitatory synapses in primary visual cortex (V1) of rodents (Kirkwood and Bear, 1994;Kirkwood et al, 1996;Desai et al, 2002;Goel et al, 2006;Keck et al, 2013). Specifically, in L2/3 neurons, removal of visually-driven activity by dark-exposure (DE) increases the amplitude of miniature excitatory postsynaptic currents (mEPSCs), while re-exposing DE mice to light for 2 h (LE) is sufficient to reduce mEPSC amplitudes to basal levels (Goel and Lee, 2007;Gao et al, 2010;Petrus et al, 2014;Chokshi et al, 2019). Mechanistically, the bidirectional homeostatic adaptation of excitatory synaptic strength in V1 is mediated by regulation of αamino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor function (Goel et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Naturalistic Spike Trains Drive State-Dependent Homeostatic Plasticity in Superficial Layers of Visual Cortex

Chokshi

Grier

Dykman

et al. 2021

Front. Synaptic Neurosci.

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The history of neural activity determines the synaptic plasticity mechanisms employed in the brain. Previous studies report a rapid reduction in the strength of excitatory synapses onto layer 2/3 (L2/3) pyramidal neurons of the primary visual cortex (V1) following two days of dark exposure and subsequent re-exposure to light. The abrupt increase in visually driven activity is predicted to drive homeostatic plasticity, however, the parameters of neural activity that trigger these changes are unknown. To determine this, we first recorded spike trains in vivo from V1 layer 4 (L4) of dark exposed (DE) mice of both sexes that were re-exposed to light through homogeneous or patterned visual stimulation. We found that delivering the spike patterns recorded in vivo to L4 of V1 slices was sufficient to reduce the amplitude of miniature excitatory postsynaptic currents (mEPSCs) of V1 L2/3 neurons in DE mice, but not in slices obtained from normal reared (NR) controls. Unexpectedly, the same stimulation pattern produced an up-regulation of mEPSC amplitudes in V1 L2/3 neurons from mice that received 2 h of light re-exposure (LE). A Poisson spike train exhibiting the same average frequency as the patterns recorded in vivo was equally effective at depressing mEPSC amplitudes in L2/3 neurons in V1 slices prepared from DE mice. Collectively, our results suggest that the history of visual experience modifies the responses of V1 neurons to stimulation and that rapid homeostatic depression of excitatory synapses can be driven by non-patterned input activity.

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Input-Specific Metaplasticity in the Visual Cortex Requires Homer1a-Mediated mGluR5 Signaling

Cited by 29 publications

References 71 publications

Mechanisms of Homeostatic Synaptic Plasticity in vivo

Mechanisms of Homeostatic Synaptic Plasticity in vivo

Restoring Glutamate receptosome dynamics at synapses rescues Autism-like deficits in Shank3-deficient mice

Naturalistic Spike Trains Drive State-Dependent Homeostatic Plasticity in Superficial Layers of Visual Cortex

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