Impaired Hippocampal Long-Term Potentiation and Memory Deficits upon Haploinsufficiency of MDGA1 Can Be Rescued by Acute Administration of D-Cycloserine DOI Open Access

Daiki Ojima,

Yoko Tominaga,

Takashi Kubôta

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9674 - 9674

Published: Sept. 6, 2024

The maintenance of proper brain function relies heavily on the balance excitatory and inhibitory neural circuits, governed in part by synaptic adhesion molecules. Among these, MDGA1 (MAM domain-containing glycosylphosphatidylinositol anchor 1) acts as a suppressor synapse formation interfering with Neuroligin-mediated interactions, crucial for maintaining excitatory–inhibitory (E/I) balance. Mdga1−/− mice exhibit selectively enhanced their hippocampal pyramidal neurons, leading to impaired long-term potentiation (LTP) hippocampus-dependent learning memory function; however, it has not been fully investigated yet if reduction protein levels would alter function. Here, we examined behavioral consequences reduced Mdga1+/− mice. As observed mice, exhibited significant deficits tasks, such Morris water maze contextual fear-conditioning tests, along deficit Schaffer collateral CA1 synapses. acute administration D-cycloserine, co-agonist NMDAR (N-methyl-d-aspartate receptor), significantly ameliorated impairments restored LTP specifically while having no effect These results highlight critical role regulating E/I cognitive findings may also suggest potential therapeutic strategies targeting imbalance alleviate associated neuropsychiatric disorders.

Language: Английский

A correlative workflow streamlines synaptic imaging by cryo-electron tomography DOI Creative Commons
Thanh Thao, Antje Siegert, Florelle Domart

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Abstract Despite decades of intense research, the molecular organization synapse is not well understood. To address this issue, we sought to develop a method for systematic imaging synapses by cryo-electron tomography (cryo-ET), technology capable mapping cellular architecture at resolution. Thinning samples cryo-focused ion beam milling prerequisite high-quality cryo-ET imaging, but process needs be guided structures interest. allow robust synaptic targeting, established correlative cryo-light/electron microscopy approach which are fluorescently labeled in minimally invasive manner, using synthetic binder postsynaptic scaffold PSD-95 and antibodies against presynaptic protein Synaptotagmin-1. Cryo-ET sites colocalization consistently revealed excitatory synapses. Our allows structural studies complexes situ , facilitating investigations

Language: Английский

Citations

0
The diverse roles of complex glycans in synapse development and function DOI Creative Commons
H. Peter Lu,

Ling‐Yu Bao,

Peng Zhang

et al.

Current Opinion in Neurobiology, Journal Year: 2025, Volume and Issue: 93, P. 103038 - 103038

Published: May 10, 2025

Protein glycosylation is a critical post-translational modification that mediates myriad of biological functions, including neuronal development in the brain. Stages include neurogenesis, migration, axonal guidance, synapse formation, and activity-dependent synaptic remodeling plasticity. Among these, formation plasticity are essential to establish maintain circuits for proper brain function. Yet, physiological role glycans at synapses remains poorly understood. This especially true complex glycans, known decades be present on cell surface or extracellular matrix, microenvironment around synapses. In this review, we highlight recent examples illustrate their roles Based these advances, propose three principal models categorize all our discussion. We hope will beneficial field begin discussion conceptual framework underlying

Language: Английский

Citations

0
Signaling by latrophilin adhesion-GPCRs in synapse assembly DOI

Thomas C. Südhof

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Impaired Hippocampal Long-Term Potentiation and Memory Deficits upon Haploinsufficiency of MDGA1 Can Be Rescued by Acute Administration of D-Cycloserine DOI Open Access

Daiki Ojima,

Yoko Tominaga,

Takashi Kubôta

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9674 - 9674

Published: Sept. 6, 2024

The maintenance of proper brain function relies heavily on the balance excitatory and inhibitory neural circuits, governed in part by synaptic adhesion molecules. Among these, MDGA1 (MAM domain-containing glycosylphosphatidylinositol anchor 1) acts as a suppressor synapse formation interfering with Neuroligin-mediated interactions, crucial for maintaining excitatory–inhibitory (E/I) balance. Mdga1−/− mice exhibit selectively enhanced their hippocampal pyramidal neurons, leading to impaired long-term potentiation (LTP) hippocampus-dependent learning memory function; however, it has not been fully investigated yet if reduction protein levels would alter function. Here, we examined behavioral consequences reduced Mdga1+/− mice. As observed mice, exhibited significant deficits tasks, such Morris water maze contextual fear-conditioning tests, along deficit Schaffer collateral CA1 synapses. acute administration D-cycloserine, co-agonist NMDAR (N-methyl-d-aspartate receptor), significantly ameliorated impairments restored LTP specifically while having no effect These results highlight critical role regulating E/I cognitive findings may also suggest potential therapeutic strategies targeting imbalance alleviate associated neuropsychiatric disorders.

Language: Английский

Citations

1