The interaction of Rabphilin-3A (Rph3A) with the NMDA receptor (NMDAR) in hippocampal neurons plays a pivotal role in the synaptic retention of this receptor. The formation of a Rph3A/NMDAR complex is needed for the induction of long-term potentiation and NMDAR-dependent hippocampal behaviors, such as spatial learning. Moreover, Rph3A can also interact with AMPA receptors (AMPARs) through the formation of a complex with myosin Va. Here, we used a confocal imaging approach to show that Rph3A overexpression in primary hippocampal neuronal cultures is sufficient to promote increased dendritic spine density. This morphological event is correlated with an increase in GluN2A-containing NMDARs at synaptic membranes and a decrease in the surface levels of GluA1-containing AMPARs. These molecular and morphological modifications of dendritic spines are sufficient to occlude the spine formation induced by long-term potentiation, but do not prevent the spine loss induced by long-term depression. Overall, our results demonstrate a key role for Rph3A in the modulation of structural synaptic plasticity at hippocampal synapses that correlates with its interactions with both NMDARs and AMPARs.

Rabphilin-3A Drives Structural Modifications of Dendritic Spines Induced by Long-Term Potentiation / L. Franchini, J. Stanic, M. Barzasi, E. Zianni, D. Mauceri, M. Diluca, F. Gardoni. - In: CELLS. - ISSN 2073-4409. - 11:10(2022 May), pp. 1616.1-1616.16. [10.3390/cells11101616]

Rabphilin-3A Drives Structural Modifications of Dendritic Spines Induced by Long-Term Potentiation

L. Franchini
Co-primo
;
J. Stanic
Co-primo
;
M. Barzasi;E. Zianni;D. Mauceri;M. Diluca
Penultimo
;
F. Gardoni
Ultimo
2022

Abstract

The interaction of Rabphilin-3A (Rph3A) with the NMDA receptor (NMDAR) in hippocampal neurons plays a pivotal role in the synaptic retention of this receptor. The formation of a Rph3A/NMDAR complex is needed for the induction of long-term potentiation and NMDAR-dependent hippocampal behaviors, such as spatial learning. Moreover, Rph3A can also interact with AMPA receptors (AMPARs) through the formation of a complex with myosin Va. Here, we used a confocal imaging approach to show that Rph3A overexpression in primary hippocampal neuronal cultures is sufficient to promote increased dendritic spine density. This morphological event is correlated with an increase in GluN2A-containing NMDARs at synaptic membranes and a decrease in the surface levels of GluA1-containing AMPARs. These molecular and morphological modifications of dendritic spines are sufficient to occlude the spine formation induced by long-term potentiation, but do not prevent the spine loss induced by long-term depression. Overall, our results demonstrate a key role for Rph3A in the modulation of structural synaptic plasticity at hippocampal synapses that correlates with its interactions with both NMDARs and AMPARs.
AMPA receptors; NMDA receptors; dendritic spines; long-term potentiation; Animals; Hippocampus; Long-Term Potentiation; Rats; Receptors, AMPA; Adaptor Proteins, Signal Transducing; Dendritic Spines; Nerve Tissue Proteins; Vesicular Transport Proteins
Settore BIO/14 - Farmacologia
PRIN201517FGARD - Targeting early synaptic dysfunctions induced by alpha-synuclein as a novel therapeutic approach in Parkinson's disease - GARDONI, FABRIZIO - PRIN2015 - PRIN bando 2015 - 2017
PRIN201719FGARD_01 - Role of alpha-synuclein and LRRK2 in Levodopa-induced dyskinesia - GARDONI, FABRIZIO - PRIN2017 - PRIN bando 2017 - 2019
11-mag-2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/937731
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