A large-scale nanoscopy and biochemistry analysis of postsynaptic dendritic spines

Helm, Martin S.; Dankovich, Tal M.; Mandad, Sunit; Rammner, Burkhard; Jähne, Sebastian; Salimi, Vanessa; Koerbs, Christina; Leibrandt, Richard; Urlaub, Henning; Schikorski, Thomas; Rizzoli, Silvio O.

doi:10.1038/s41593-021-00874-w

Cited by 83 publications

(86 citation statements)

References 73 publications

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“…Mushroom spines, the ones with large head and thin neck, are considered to be responsible for memory formation and learning processes ( Bourne and Harris, 2007 , Hayashi and Majewska, 2005 ). They have larger postsynaptic density (PSD) then other types which help them form strong synaptic connections ( Helm et al, 2021 ). A decrease in mushroom spines makes these synapses functionally weaker which leads to cognitive impairment ( Tackenberg et al, 2009 ).…”

Section: Resultsmentioning

confidence: 99%

CaMKIIβ knockdown decreases store-operated calcium entry in hippocampal dendritic spines

Zernov

Bezprozvanny

Попугаева

2022

IBRO Neuroscience Reports

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Calcium/calmodulin-dependent protein kinase II (CaMKII) and neuronal store-operated calcium entry (nSOCE) have been implicated in the development of Alzheimer's disease (AD). nSOCE is involved in regulation of dendritic spine shape, particularly in stability of mushroom spines that play role in formation of strong synapses. CaMKII is involved in regulation of induction of long-term potentiation, that is needed for shaping of memory. In the present study, we demonstrated that inhibition of kinase activity of CaMKII by KN-62 decreases nSOCE amplitude in soma of primary hippocampal neurons. We have shown that knockdown of CaMKIIβ leads to the downregulation of nSOCE in dendritic spines. In agreement with previously published data, we have also observed that CaMKIIβ knockdown causes mushroom spine loss in primary hippocampal culture. The effect of CaMKIIβ knockdown on the nSOCE may be associated with a decrease of dendritic spine head size.

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Section: Resultsmentioning

confidence: 99%

CaMKIIβ knockdown decreases store-operated calcium entry in hippocampal dendritic spines

Zernov

Bezprozvanny

Попугаева

2022

IBRO Neuroscience Reports

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“…The role of stubby dendritic spines is still poorly understood, and they are considered formed, mainly due to the disappearance of mushroom spines. Recent studies have shown that stubby and mushroom spines have similar mean protein copy numbers and topology [ 57 ], which also suggests that stubby spine density is related to changes in mushroom density.…”

Section: Discussionmentioning

confidence: 99%

Synaptamide Improves Cognitive Functions and Neuronal Plasticity in Neuropathic Pain

Tyrtyshnaia

Bondar

Konovalova

et al. 2021

IJMS

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Neuropathic pain arises from damage or dysfunction of the peripheral or central nervous system and manifests itself in a wide variety of sensory symptoms and cognitive disorders. Many studies demonstrate the role of neuropathic pain-induced neuroinflammation in behavioral disorders. For effective neuropathic pain treatment, an integrative approach is required, which simultaneously affects several links of pathogenesis. One promising candidate for this role is synaptamide (N-docosahexaenoylethanolamine), which is an endogenous metabolite of docosahexaenoic acid. In this study, we investigated the activity of synaptamide on mice behavior and hippocampal plasticity in neuropathic pain induced by spared nerve injury (SNI). We found a beneficial effect of synaptamide on the thermal allodynia and mechanical hyperalgesia dynamics. Synaptamide prevented working and long-term memory impairment. These results are probably based on the supportive effect of synaptamide on SNI-impaired hippocampal plasticity. Nerve ligation caused microglia activation predominantly in the contralateral hippocampus, while synaptamide inhibited this effect. The treatment reversed dendritic tree degeneration, dendritic spines density reduction on CA1-pyramidal neurons, neurogenesis deterioration, and hippocampal long-term potentiation (LTP) impairment. In addition, synaptamide inhibits changes in the glutamatergic receptor expression. Thus, synaptamide has a beneficial effect on hippocampal functioning, including synaptic plasticity and hippocampus-dependent cognitive processes in neuropathic pain.

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“…SMLM was later used to investigate the nanoclustering behaviour of individual molecular players at the presynapse in vivo and in vitro [69][70][71][72]. STED as well as SMLM have been used to image dendritic spines and postsynaptic structures in cultured cells and brain slices [73][74][75][76][77][78][79]. Recently, STED has been employed to illuminate spine dynamics in living mice [80][81][82][83][84][85][86].…”

Section: Super-resolution Methodsmentioning

confidence: 99%

Super-resolution imaging to reveal the nanostructure of tripartite synapses

Aleksejenko

Heller

2021

Neuronal Signaling

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Even though neurons are the main drivers of information processing in the brain and spinal cord, other cell types are important to mediate adequate flow of information. These include electrically-passive glial cells such as microglia and astrocytes, which recently emerged as active partners facilitating proper signal transduction. In disease, these cells undergo pathophysiological changes that propel disease progression and change synaptic connections and signal transmission. In the healthy brain, astrocytic processes contact pre- and postsynaptic structures. These processes can be nanoscopic, and therefore only electron microscopy has been able to reveal their structure and morphology. However, electron microscopy is not suitable in revealing dynamic changes, and it is labour- and time-intensive. The dawn of super-resolution microscopy, techniques that ‘break’ the diffraction limit of conventional light microscopy, over the last decades has enabled researchers to reveal the nanoscopic synaptic environment. In this review, we highlight and discuss recent advances in our understanding of the nano-world of the so-called tripartite synapses, the relationship between pre- and postsynapse as well as astrocytic processes. Overall, novel super-resolution microscopy methods are needed to fully illuminate the intimate relationship between glia and neuronal cells that underlies signal transduction in the brain and that might be affected in diseases such as Alzheimer’s disease and epilepsy.

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A large-scale nanoscopy and biochemistry analysis of postsynaptic dendritic spines

Cited by 83 publications

References 73 publications

CaMKIIβ knockdown decreases store-operated calcium entry in hippocampal dendritic spines

CaMKIIβ knockdown decreases store-operated calcium entry in hippocampal dendritic spines

Synaptamide Improves Cognitive Functions and Neuronal Plasticity in Neuropathic Pain

Super-resolution imaging to reveal the nanostructure of tripartite synapses

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