Differential nanoscale organization of excitatory synapses onto excitatory vs. inhibitory neurons.
Proc Natl Acad Sci U S A
; 121(17): e2315379121, 2024 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-38625946
ABSTRACT
A key feature of excitatory synapses is the existence of subsynaptic protein nanoclusters (NCs) whose precise alignment across the cleft in a transsynaptic nanocolumn influences the strength of synaptic transmission. However, whether nanocolumn properties vary between excitatory synapses functioning in different cellular contexts is unknown. We used a combination of confocal and DNA-PAINT super-resolution microscopy to directly compare the organization of shared scaffold proteins at two important excitatory synapses-those forming onto excitatory principal neurons (ExâEx synapses) and those forming onto parvalbumin-expressing interneurons (ExâPV synapses). As in ExâEx synapses, we find that in ExâPV synapses, presynaptic Munc13-1 and postsynaptic PSD-95 both form NCs that demonstrate alignment, underscoring synaptic nanostructure and the transsynaptic nanocolumn as conserved organizational principles of excitatory synapses. Despite the general conservation of these features, we observed specific differences in the characteristics of pre- and postsynaptic ExâPV nanostructure. ExâPV synapses contained larger PSDs with fewer PSD-95 NCs when accounting for size than ExâEx synapses. Furthermore, the PSD-95 NCs were larger and denser. The identity of the postsynaptic cell was also represented in Munc13-1 organization, as ExâPV synapses hosted larger Munc13-1 puncta that contained less dense but larger and more numerous Munc13-1 NCs. Moreover, we measured the spatial variability of transsynaptic alignment in these synapse types, revealing protein alignment in ExâPV synapses over a distinct range of distances compared to ExâEx synapses. We conclude that while general principles of nanostructure and alignment are shared, cell-specific elements of nanodomain organization likely contribute to functional diversity of excitatory synapses.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinapses
/
Neurônios
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2024
Tipo de documento:
Article