A Single-synapse Resolution Survey of PSD95-positive Synapses in Twenty Human Brain Regions

Overview

Journal Eur J Neurosci

Specialty Neurology

Date 2020 Jun 4

PMID 32492218

Citations 14

Authors

Olimpia E Curran

Zhen Qiu

Colin Smith

Seth G N Grant

Affiliations

Soon will be listed here.

Abstract

Mapping the molecular composition of individual excitatory synapses across the mouse brain reveals high synapse diversity with each brain region showing a distinct composition of synapse types. As a first step towards systematic mapping of synapse diversity across the human brain, we have labelled and imaged synapses expressing the excitatory synapse protein PSD95 in twenty human brain regions, including 13 neocortical, two subcortical, one hippocampal, one cerebellar and three brainstem regions, in four phenotypically normal individuals. We quantified the number, size and intensity of individual synaptic puncta and compared their regional distributions. We found that each region showed a distinct signature of synaptic puncta parameters. Comparison of brain regions showed that cortical and hippocampal structures are similar, and distinct from those of cerebellum and brainstem. Comparison of synapse parameters from human and mouse brain revealed conservation of parameters, hierarchical organization of brain regions and network architecture. This work illustrates the feasibility of generating a systematic single-synapse resolution atlas of the human brain, a potentially significant resource in studies of brain health and disease.

Citing Articles

Limited evidence for anatomical contacts between intestinal GLP-1 cells and vagal neurons in male mice.

Cao N, Merchant W, Gautron L Sci Rep. 2024; 14(1):23666.

PMID: 39390033 PMC: 11467209. DOI: 10.1038/s41598-024-74000-8.

Heat stress induces calcium dyshomeostasis to subsequent cognitive impairment through ERS-mediated apoptosis via SERCA/PERK/eIF2α pathway.

Li H, Pan W, Li C, Cai M, Shi W, Ren Z Cell Death Discov. 2024; 10(1):280.

PMID: 38862478 PMC: 11167007. DOI: 10.1038/s41420-024-02047-7.

Intranasal CEPO-FC prevents attention deficits in streptozotocin-induced rat model of Alzheimer's disease: Focus on synaptic plasticity-related factors.

Mansouri Z, Khodagholi F, Zaringhalam J, Abbaszadeh F, Ghasemi R, Maghsoudi N EXCLI J. 2024; 23:491-508.

PMID: 38741725 PMC: 11089095. DOI: 10.17179/excli2023-6818.

Training-induced circuit-specific excitatory synaptogenesis in mice is required for effort control.

Ulloa Severino F, Lawal O, Sakers K, Wang S, Kim N, Friedman A Nat Commun. 2023; 14(1):5522.

PMID: 37684234 PMC: 10491649. DOI: 10.1038/s41467-023-41078-z.

Cell-Type-Specific Neuroproteomics of Synapses.

Yim Y, Nestler E Biomolecules. 2023; 13(6).

PMID: 37371578 PMC: 10296650. DOI: 10.3390/biom13060998.

References

Nithianantharajah J, Komiyama N, McKechanie A, Johnstone M, Blackwood D, St Clair D . Synaptic scaffold evolution generated components of vertebrate cognitive complexity. Nat Neurosci. 2012; 16(1):16-24. PMC: 4131247. DOI: 10.1038/nn.3276. View

Frank R, Grant S . Supramolecular organization of NMDA receptors and the postsynaptic density. Curr Opin Neurobiol. 2017; 45:139-147. PMC: 5557338. DOI: 10.1016/j.conb.2017.05.019. View

Grant S, Marshall M, Page K, Cumiskey M, Armstrong J . Synapse proteomics of multiprotein complexes: en route from genes to nervous system diseases. Hum Mol Genet. 2005; 14 Spec No. 2:R225-34. DOI: 10.1093/hmg/ddi330. View

Camp M, Feyder M, Ihne J, Palachick B, Hurd B, Karlsson R . A novel role for PSD-95 in mediating ethanol intoxication, drinking and place preference. Addict Biol. 2011; 16(3):428-39. PMC: 3150485. DOI: 10.1111/j.1369-1600.2010.00282.x. View

Carlisle H, Fink A, Grant S, ODell T . Opposing effects of PSD-93 and PSD-95 on long-term potentiation and spike timing-dependent plasticity. J Physiol. 2008; 586(24):5885-900. PMC: 2655416. DOI: 10.1113/jphysiol.2008.163469. View

Fagiolini M, Katagiri H, Miyamoto H, Mori H, Grant S, Mishina M . Separable features of visual cortical plasticity revealed by N-methyl-D-aspartate receptor 2A signaling. Proc Natl Acad Sci U S A. 2003; 100(5):2854-9. PMC: 151430. DOI: 10.1073/pnas.0536089100. View

Husi H, Ward M, Choudhary J, Blackstock W, Grant S . Proteomic analysis of NMDA receptor-adhesion protein signaling complexes. Nat Neurosci. 2000; 3(7):661-9. DOI: 10.1038/76615. View

Komiyama N, Watabe A, Carlisle H, Porter K, Charlesworth P, Monti J . SynGAP regulates ERK/MAPK signaling, synaptic plasticity, and learning in the complex with postsynaptic density 95 and NMDA receptor. J Neurosci. 2002; 22(22):9721-32. PMC: 6757832. View

Emes R, Pocklington A, Anderson C, Bayes A, Collins M, Vickers C . Evolutionary expansion and anatomical specialization of synapse proteome complexity. Nat Neurosci. 2008; 11(7):799-806. PMC: 3624047. DOI: 10.1038/nn.2135. View

10.

Ryan T, Kopanitsa M, Indersmitten T, Nithianantharajah J, Afinowi N, Pettit C . Evolution of GluN2A/B cytoplasmic domains diversified vertebrate synaptic plasticity and behavior. Nat Neurosci. 2012; 16(1):25-32. PMC: 3979286. DOI: 10.1038/nn.3277. View

11.

Migaud M, Charlesworth P, Dempster M, Webster L, Watabe A, Makhinson M . Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein. Nature. 1998; 396(6710):433-9. DOI: 10.1038/24790. View

12.

Roy M, Sorokina O, McLean C, Tapia-Gonzalez S, DeFelipe J, Armstrong J . Regional Diversity in the Postsynaptic Proteome of the Mouse Brain. Proteomes. 2018; 6(3). PMC: 6161190. DOI: 10.3390/proteomes6030031. View

13.

Schnell S, Staines W, Wessendorf M . Reduction of lipofuscin-like autofluorescence in fluorescently labeled tissue. J Histochem Cytochem. 1999; 47(6):719-30. DOI: 10.1177/002215549904700601. View

14.

Koffie R, Meyer-Luehmann M, Hashimoto T, Adams K, Mielke M, Garcia-Alloza M . Oligomeric amyloid beta associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Proc Natl Acad Sci U S A. 2009; 106(10):4012-7. PMC: 2656196. DOI: 10.1073/pnas.0811698106. View

15.

Fromer M, Pocklington A, Kavanagh D, Williams H, Dwyer S, Gormley P . De novo mutations in schizophrenia implicate synaptic networks. Nature. 2014; 506(7487):179-84. PMC: 4237002. DOI: 10.1038/nature12929. View

16.

Fourie C, Kim E, Waldvogel H, Wong J, McGregor A, Faull R . Differential Changes in Postsynaptic Density Proteins in Postmortem Huntington's Disease and Parkinson's Disease Human Brains. J Neurodegener Dis. 2015; 2014:938530. PMC: 4437361. DOI: 10.1155/2014/938530. View

17.

van de Lagemaat L, Stanford L, Pettit C, Strathdee D, Strathdee K, Elsegood K . Standardized experiments in mutant mice reveal behavioural similarity on 129S5 and C57BL/6J backgrounds. Genes Brain Behav. 2016; 16(4):409-418. DOI: 10.1111/gbb.12364. View

18.

Sinclair L, Tayler H, Love S . Synaptic protein levels altered in vascular dementia. Neuropathol Appl Neurobiol. 2015; 41(4):533-43. PMC: 4471617. DOI: 10.1111/nan.12215. View

19.

Krzywinski M, Altman N . Visualizing samples with box plots. Nat Methods. 2014; 11(2):119-20. DOI: 10.1038/nmeth.2813. View

20.

King A, Maekawa S, Bodi I, Troakes C, Curran O, Ashkan K . Simulated surgical-type cerebral biopsies from post-mortem brains allows accurate neuropathological diagnoses in the majority of neurodegenerative disease groups. Acta Neuropathol Commun. 2013; 1:53. PMC: 3893367. DOI: 10.1186/2051-5960-1-53. View