Cryo-electron tomographic investigation of native hippocampal glutamatergic synapses

Matsui, Aya; Spangler, Cathy J.; Elferich, Johannes; Shiozaki, Momoko; Jean, Nikki; Zhao, Xiaowei; Qin, Maozhen; Zhong, Haining; Yu, Zhiheng; Gouaux, Eric

doi:10.1101/2024.04.01.587595

Cited by 3 publications

(1 citation statement)

References 43 publications

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“…This study identified the existence of trans-synaptic nanocolumns, which co-organize the pre-synaptic release machinery in register with post-synaptic AMPARs and improve the efficiency of synaptic transmission [87,88] (figure 1b,c). Interestingly, the recent developments in cryo-electron tomography have allowed the ultrastructural visualization of these protein nanodomains and trans-synaptic assemblies [102][103][104][105][106][107][108]. The burning question that thus arose was: what are the underlying molecular elements that bridge pre-and post-synaptic nanodomains?…”

Section: Post-synaptic Nano-organization and Trans-synaptic Complexes...mentioning

confidence: 99%

Activity-dependent diffusion trapping of AMPA receptors as a key step for expression of early LTP

Nowacka,

Getz,

Bessa-Neto

et al. 2024

Phil. Trans. R. Soc. B

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This review focuses on the activity-dependent diffusion trapping of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as a crucial mechanism for the expression of early long-term potentiation (LTP), a process central to learning and memory. Despite decades of research, the precise mechanisms by which LTP induction leads to an increase in AMPAR responses at synapses have been elusive. We review the different hypotheses that have been put forward to explain the increased AMPAR responsiveness during LTP. We discuss the dynamic nature of AMPAR complexes, including their constant turnover and activity-dependent modifications that affect their synaptic accumulation. We highlight a hypothesis suggesting that AMPARs are diffusively trapped at synapses through activity-dependent interactions with protein-based binding slots in the post-synaptic density (PSD), offering a potential explanation for the increased synaptic strength during LTP. Furthermore, we outline the challenges still to be addressed before we fully understand the functional roles and molecular mechanisms of AMPAR dynamic nanoscale organization in LTP. This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.

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Section: Post-synaptic Nano-organization and Trans-synaptic Complexes...mentioning

confidence: 99%

Activity-dependent diffusion trapping of AMPA receptors as a key step for expression of early LTP

Nowacka,

Getz,

Bessa-Neto

et al. 2024

Phil. Trans. R. Soc. B

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Bridging structural biology and clinical research through in-tissue cryo-electron tomography

Kixmoeller,

Creekmore,

Lee

et al. 2024

EMBO J

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Structural biology is a field of research that investigates the structure and organization of macromolecules to decipher their functional mechanisms. Traditionally, it has adopted a reductionist approach out of necessity, focusing on the high-resolution analysis of macromolecules outside their natural cellular contexts. This contrasts sharply with clinical research, which examines human biology holistically through patient studies and cellular disease models, albeit with less detailed structural insights. Recent advancements are bridging this gap, enabling the study of macromolecular structures within more complex biological systems, from single cells to multicellular organisms and primary human tissues. These developments signal a pivotal shift within structural biology from traditional methodologies towards a more integrated understanding of biological complexity. Here, we highlight recent technological advancements that facilitate structural studies in tissue environments, showcasing the discoveries made possible with these approaches and the prospect of their applications in human clinical research.

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Charting the molecular landscape of neuronal organisation within the hippocampus using cryo electron tomography

Glynn,

Smith,

Case

et al. 2024

Preprint

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Cellular cryo-electron tomography (cryoET) enables the capture of detailed structural information within a biologically relevant environment. However, information in more complex samples, such as tissues, is lacking. Importantly, these observations need to be set in context of populations; imaging on the molecular scale to-date is limited to few observations in-situ that struggle to be generalised. This is due to limitations in throughput and versatility employed by current instrumentation. Here, we utilise plasma focused ion beam milling to examine the molecular landscape of mouse hippocampus by cryoET in targeted regions across multiple individuals revealing the complex organisation of macromolecules from the CA1 strata pyramidale (sp) to radiatum (sr). Our data represent a molecular atlas, producing snapshots of hippocampal architecture in adult mouse. The combination of instrumentation and application of technical advancements provides a framework to explore specific structural questions within native tissues in a targeted manner.

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Cryo-electron tomographic investigation of native hippocampal glutamatergic synapses

Cited by 3 publications

References 43 publications

Activity-dependent diffusion trapping of AMPA receptors as a key step for expression of early LTP

Activity-dependent diffusion trapping of AMPA receptors as a key step for expression of early LTP

Bridging structural biology and clinical research through in-tissue cryo-electron tomography

Charting the molecular landscape of neuronal organisation within the hippocampus using cryo electron tomography

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