DA levels and corticostriatal synaptic plasticity; functional recovery using TAT2A

Noted on Tuesday, Oct 20

Title: Distinct levels of dopaminergic denervation differentially alter striatal synaptic plasticity and NMDA receptor subunit composition: Implications for Parkinson’s disease therapy

Authors: B. PICCONI, V. BAGETTA, V. PAILLÉ, V. GHIGLIERI, C. SGOBIO, I. BARONE, M. DI FILIPPO, M. VISCOMI, F. GARDONI, G. BERNARDI, P. GREENGARD, M. DI LUCA, P. CALABRESI

Sorry for posting this a day late.

Picconi et al. were looking at the interaction between NMDA and DA transmission in the striatum particularly in a model of "early PD", where partial denervation selectively disrupted NMDA-dependant LTP, but not LTD, accompanied by mild motor deficits.  They demonstrated  that corticostraiatal synaptic plasticity actually depends on how much DA levels are decreased.  Furthermore, using TAT2A (a cell-permeable peptide) they were able to rescue the  NMDA receptors, synaptic plasticity, and the motor deficits observed. Since the abundance, structure, and function of striatal receptors are altered by the dopamine depletion in PD, this peptide may offer a novel therapeutic approach by targetting NMDA receptor signaling.