Endoplasmic reticulum visits highly active spines and prevents runaway potentiation of synapses

Pérez-Álvarez, Alberto; Yin, Shuting; Schulze, Christian; Hammer, John A.; Wagner, Wolfgang; Oertner, Thomas G.

doi:10.1038/s41467-020-18889-5

Cited by 59 publications

(52 citation statements)

References 69 publications

(98 reference statements)

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“…We found that Golgi is exclusively labeled in the DD cell bodies ( Figure S1.4A ). In contrast, mitochondria and rough ER are dispersed throughout the main dendritic shaft and near the base of spines ( Figure S1.4B-E ), perhaps suggesting involvement in spine function (Perez-Alvarez et al, 2020) (Z. Li et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components

Oliver

Ramachandran

Philbrook

et al. 2021

Preprint

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A high degree of cell and circuit-specific regulation has complicated efforts to precisely define roles for synaptic adhesion proteins in establishing circuit connectivity. Here, we take advantage of the strengths of C. elegans for cell-specific analyses to investigate molecular coordination of pre- and postsynaptic development. We show that developing dendritic spines emerge from the dendrites of wild type GABAergic motor neurons following the localization of active zone proteins and the formation of immature synaptic vesicle assemblies in presynaptic terminals. Similarly, clusters of postsynaptic receptors and F-actin are visible in GABAergic dendrites prior to spine outgrowth. Surprisingly, these developmental processes occur without a requirement for synaptic activity. Likewise, the initial stages of spine outgrowth and receptor clustering are not altered by deletion of the C. elegans ortholog of the transsynaptic adhesion protein, neurexin/NRX-1. Over time, however, dendritic spines and postsynaptic receptor clusters are destabilized in the absence of presynaptic NRX-1/neurexin and collapse prior to adulthood. The kinesin-3 family member, UNC-104, delivers NRX-1 to presynaptic terminals and ongoing UNC-104 delivery is required into adulthood for the maintenance of postsynaptic structure. Our findings provide novel insights into the temporal order of synapse formation events in vivo and demonstrate a requirement for transsynaptic adhesion in stabilizing mature circuit connectivity.

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Section: Resultsmentioning

confidence: 99%

Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components

Oliver

Ramachandran

Philbrook

et al. 2021

Preprint

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“…Such synapse-specific regulations are in agreement with the non-uniform distribution of SP, which likely serves as a molecular tag enabling individual synapses to undergo potentiation. The appearance of SP clusters likely reflects the elaboration and the stabilization of the spine apparatus (Perez-Alvarez et al, 2020) that is, together with the presence of polyribosomes, predictive of activity-dependent spine enlargement (Chirillo et al, 2019). The fact that SP enables individual synapses to undergo potentiation in both Hebbian and homeostatic forms of plasticity underscores its fundamental role and raises the possibility that both types of plasticity coexist and/or occlude each other at individual synapses, possibly reflecting a shift in homeostatic setpoint and/or LTP sliding threshold (Galanis and Vlachos, 2020; Lee and Kirkwood, 2019; Li et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

mir124-dependent tagging of glutamatergic synapses by synaptopodin controls non-uniform and input-specific homeostatic synaptic plasticity

Dubes

Soula

Benquet

et al. 2021

Preprint

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Homeostatic synaptic plasticity (HSP) is a process by which neurons adjust synaptic strengths to compensate for various perturbations and which allows to stabilize neuronal activity. Yet, whether the highly diverse synapses harboring a neuron respond uniformly to a same perturbation is unclear and the underlying molecular determinants remain to be identified. Here, using patch-clamp recordings, immunolabeling and imaging approaches, we report that the ability of individual synapses to undergo HSP in response to activity-deprivation paradigms depends on the local expression of the spine apparatus related protein synaptopodin (SP) acting as a synaptic tag to promote AMPA receptor synaptic accumulation and spine growth. Gain and loss-of-function experiments indicate that this process relies on the local de-repression of SP translation by miR124 which supports both non-uniform and synapse-autonomous HSP induced by global or input-specific activity deprivation, respectively. Our findings uncover an unexpected synaptic-tagging mechanism for HSP, whose molecular actors are intriguingly shared with Hebbian plasticity and linked to multiple neurological diseases.

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“…Spine apparatus, which is composed of stacked SER, is present in 10–20% of spines. Localizations of these organelles change after LTP induction, and spines containing SER are larger than those without SER ( Chirillo et al, 2019 ; Kulik et al, 2019 ; Perez-Alvarez et al, 2020 ). While mitochondria are abundant in dendritic shafts but rarely present in spines ( Wu et al, 2017 ), synaptic activation relocates mitochondria into spines ( Li et al, 2004 ).…”

Section: Membranous Organellesmentioning

confidence: 99%

The role of molecular diffusion within dendritic spines in synaptic function

Obashi

Taraska

Okabe

2021

Journal of General Physiology

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Spines are tiny nanoscale protrusions from dendrites of neurons. In the cortex and hippocampus, most of the excitatory postsynaptic sites reside in spines. The bulbous spine head is connected to the dendritic shaft by a thin membranous neck. Because the neck is narrow, spine heads are thought to function as biochemically independent signaling compartments. Thus, dynamic changes in the composition, distribution, mobility, conformations, and signaling properties of molecules contained within spines can account for much of the molecular basis of postsynaptic function and regulation. A major factor in controlling these changes is the diffusional properties of proteins within this small compartment. Advances in measurement techniques using fluorescence microscopy now make it possible to measure molecular diffusion within single dendritic spines directly. Here, we review the regulatory mechanisms of diffusion in spines by local intra-spine architecture and discuss their implications for neuronal signaling and synaptic plasticity.

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Endoplasmic reticulum visits highly active spines and prevents runaway potentiation of synapses

Cited by 59 publications

References 69 publications

Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components

Kinesin-3 mediated axonal delivery of presynaptic neurexin stabilizes dendritic spines and postsynaptic components

mir124-dependent tagging of glutamatergic synapses by synaptopodin controls non-uniform and input-specific homeostatic synaptic plasticity

The role of molecular diffusion within dendritic spines in synaptic function

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