Trans-synaptic molecular context of NMDA receptor nanodomains DOI Creative Commons
Michael Anderson, Poorna A. Dharmasri, Martina Damenti

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 23, 2023

Tight coordination of the spatial relationships between protein complexes is required for cellular function. In neuronal synapses, many proteins responsible neurotransmission organize into subsynaptic nanoclusters whose trans-cellular alignment modulates synaptic signal propagation. However, these and NMDA receptors (NMDARs), which are learning memory, remain undefined. Here, we mapped relationship key NMDAR subunits to reference in active zone postsynaptic density using multiplexed super-resolution DNA-PAINT microscopy. GluN2A GluN2B formed with diverse configurations that, surprisingly, were not localized near presynaptic vesicle release sites marked by Munc13-1. a subset was configured maintain activation: internally denser, aligned abundant PSD-95, associated closely specific nanodomains. This work reveals new principle regulating signaling suggests that functional architecture depends on assembly multiprotein nanodomains interior construction conditional relationships.

Language: Английский

Contrasting patterns of extrasynaptic NMDAR-GluN2B expression in macaque subgenual cingulate and dorsolateral prefrontal cortices DOI Open Access
Mary Kate P. Joyce,

D. Datta,

J.L. Pérez-Arellano

et al.

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

Published: Feb. 6, 2025

Abstract Expression of the N-methyl-D-aspartate receptor, particularly when containing GluN2B subunit (NMDAR-GluN2B) varies across prefrontal cortex (PFC). In humans, subgenual cingulate (SGC) contains among highest levels NMDAR-GluN2B expression, while dorsolateral (dlPFC) exhibits a more moderate level expression. are commonly associated with ionotropic synaptic function and plasticity, essential to neurotransmission underlying working memory in macaque dlPFC layer III circuits afflicted schizophrenia. However, can also be found at extrasynaptic sites, where they may trigger distinct events, including some linked neurodegenerative processes. The SGC is an early site tau pathology sporadic Alzheimer’s Disease (sAD), which mirrors its high Additionally, hyperactive depression, treated NMDAR antagonists. Given clinical relevance dlPFC, current study used immunoelectron microscopy (immunoEM) quantitatively compare expression patterns excitatory inhibitory neuron dendrites rhesus dlPFC. We larger population dendritic shafts spines putative pyramidal neurons as compared had higher proportion NMDAR-GluN2B. contrast, from both areas, was far frequently observed over These findings provide insight into varying cortical vulnerability alterations excitability forces. Scope Statement receptors that contribute second messenger signaling events. induce diverse array neuronal part due variation composition subcellular localization receptor humans. This highly expressed cingulate, area mood emotion, moderately cortex, cognitive Extrasynaptic NMDAR, often contain subunit, have been detrimental cellular events like neurodegeneration. Here, using resolution electron macaques, we evidence prominent than cortex. Conversely, consistent their contribution firing during memory. help illuminate propensity tonic hyperactivity major depression neurodegeneration disease, explain how rapid acting antidepressants exert therapeutic action neural circuits.

Language: Английский

Citations

0
Regulation of Synaptic NMDA Receptor Activity by Post-Translational Modifications DOI Creative Commons
Emanuel Tahiri, Elisa Corti, Carlos B. Duarte

et al.

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(2)

Published: March 3, 2025

Language: Английский

Citations

0
Contrasting patterns of extrasynaptic NMDAR-GluN2B expression in macaque subgenual cingulate and dorsolateral prefrontal cortices DOI Creative Commons
Mary Kate P. Joyce, Dibyadeep Datta, Jon I. Arellano

et al.

Frontiers in Neuroanatomy, Journal Year: 2025, Volume and Issue: 19

Published: April 4, 2025

Expression of the N-methyl-D-aspartate receptor, particularly when containing GluN2B subunit (NMDAR-GluN2B), varies across prefrontal cortex (PFC). In humans, subgenual cingulate (SGC) contains among highest levels NMDAR-GluN2B expression, while dorsolateral (dlPFC) exhibits a more moderate level expression. are commonly associated with ionotropic synaptic function and plasticity essential to neurotransmission underlying working memory in macaque dlPFC layer III circuits, which humans afflicted schizophrenia. However, can also be found at extrasynaptic sites, where they may trigger distinct events, including some linked neurodegenerative processes. The SGC is an early site tau pathology sporadic Alzheimer’s disease (sAD), mirrors its high Additionally, hyperactive depression, treated NMDAR antagonists. Given clinical relevance dlPFC, current study used immunoelectron microscopy (immunoEM) quantitatively compare expression patterns excitatory inhibitory neuron dendrites rhesus dlPFC. We larger population putative pyramidal neurons as compared had higher proportion NMDAR-GluN2B. contrast, from both areas, was far frequently observed over These findings provide insight into varying cortical vulnerability alterations excitability forces.

Language: Английский

Citations

0
Trans-synaptic molecular context of NMDA receptor nanodomains DOI Creative Commons
Michael Anderson, Poorna A. Dharmasri, Martina Damenti

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 23, 2023

Tight coordination of the spatial relationships between protein complexes is required for cellular function. In neuronal synapses, many proteins responsible neurotransmission organize into subsynaptic nanoclusters whose trans-cellular alignment modulates synaptic signal propagation. However, these and NMDA receptors (NMDARs), which are learning memory, remain undefined. Here, we mapped relationship key NMDAR subunits to reference in active zone postsynaptic density using multiplexed super-resolution DNA-PAINT microscopy. GluN2A GluN2B formed with diverse configurations that, surprisingly, were not localized near presynaptic vesicle release sites marked by Munc13-1. a subset was configured maintain activation: internally denser, aligned abundant PSD-95, associated closely specific nanodomains. This work reveals new principle regulating signaling suggests that functional architecture depends on assembly multiprotein nanodomains interior construction conditional relationships.

Language: Английский

Citations

3