Neuroligin-3 confines AMPA receptors into nanoclusters, thereby controlling synaptic strength at the calyx of Held synapses
0301 basic medicine
570
0303 health sciences
03 medical and health sciences
Underpinning research
1.1 Normal biological development and functioning
Neurosciences
Brain Disorders
Neuroscience
DOI:
10.1126/sciadv.abo4173
Publication Date:
2022-06-15T17:53:55Z
AUTHORS (7)
ABSTRACT
The subsynaptic organization of postsynaptic neurotransmitter receptors into nanoclusters that are aligned with presynaptic release sites is essential for the high fidelity of synaptic transmission. However, the mechanisms controlling the nanoscale organization of neurotransmitter receptors in vivo remain incompletely understood. Here, we deconstructed the role of neuroligin-3 (Nlgn3), a postsynaptic adhesion molecule linked to autism, in organizing AMPA-type glutamate receptors in the calyx of Held synapse. Deletion of
Nlgn3
lowered the amplitude and slowed the kinetics of AMPA receptor–mediated synaptic responses. Super-resolution microscopy revealed that, unexpectedly, these impairments in synaptic transmission were associated with an increase in the size of postsynaptic PSD-95 and AMPA receptor nanoclusters but a decrease of the densities in these clusters. Modeling showed that a dilution of AMPA receptors into larger nanocluster volumes decreases synaptic strength. Nlgn3, likely by binding to presynaptic neurexins, thus is a key organizer of AMPA receptor nanoclusters that likely acts via PSD-95 adaptors to optimize the fidelity of synaptic transmission.
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