NMDA receptor synaptic retention: from synaptic plasticity to Parkinson’s disease- Fabrizio Gardoni- 19/6/2019


NMDA receptor synaptic retention: from synaptic plasticity  to Parkinson’s disease

Prof.  Fabrizio Gardoni (Dept. Pharmacological and Biomolecular Sciences (DiSFeB) University of Milano)


19 JUNE  2019,  12.00 – 13.00

Monterotondo CNR Seminar Room, Building 21



NMDA receptor subunit composition plays a pivotal role in synaptic plasticity at excitatory synapses. Still, the molecular mechanisms responsible for the synaptic retention of NMDA receptor subtypes following induction of synaptic plasticity need to be fully elucidated.

Here we show that Rabphilin3A (Rph3A) is involved in the stabilization of NMDA receptors at synapses through the formation of a complex with the GluN2A subunit. Induction of long-term potentiation (LTP) led to synaptic accumulation of Rph3A and formation of synaptic GluN2A/Rph3A complex. These events were strictly modulated by mGluR5-phospholipase C pathway. Notably, interfering with the GluN2A/Rph3A complex blocks induction of LTP as well as LTP-dependent modifications of dendritic spines. Moreover, in vivo disruption of GluN2A/Rph3A complex led to a profound alteration of spatial memory.

Finally, our findings indicate that Rph3A activity is linked to the aberrant synaptic localization of GluN2A-expressing NMDARs characterizing experimental models of Parkinson’s Disease and L-DOPA-induced dyskinesia. Thus, we suggest that Rph3A/GluN2A complex could represent an innovative therapeutic target for those pathological conditions where NMDAR composition is significantly altered.



  • Rph3A retains NMDA receptors at synaptic sites
  • GluN2A/Rph3A complex is needed for induction of synaptic plasticity and spatial memory
  • Disrupting GluN2A/Rph3A interaction ameliorates L-DOPA-induced dyskinetic behaviour


Host: Dr. Elvira De Leonibus


data evento: 
Mercoledì, 19 Giugno, 2019
Fabrizio Gardoni
tipo evento: 

© Università degli Studi di Roma "La Sapienza" - Piazzale Aldo Moro 5, 00185 Roma