We documented spine loss for the three types of striatal MSNs, in accordance with data obtained for D1 and the D2 MSNs in mice333561, rats606263, monkeys36 and PD patients3738. Interestingly, other studies have suggested that such spine loss may be restricted to the D2 MSNs in mice3132. As mentioned above, DA axons are ideally positioned on the dendritic spine neck to influence the effect of corticostriatal and thalamostriatal glutamatergic input56. It has been hypothesized that the loss of DA afferents may destabilize the morphological integrity of the spine, potentially leading to spine pruning, a phenomenon that might be the result of maladaptive calcium influx through the L-type calcium channels located on MSNs31. Moreover, evidence has recently been gathered regarding the implication of acetylcholine, the level of which is known to be increased in PD6465, in spine pruning of the D2 MSNs through the modulation of Kir2 channels, leading to an increase of dendritic excitability driven by the activation of M1 muscarinic receptor32.
