| First Author | Zhai S | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 8 | Pages | 114540 |
| PubMed ID | 39058595 | Mgi Jnum | J:353799 |
| Mgi Id | MGI:7716357 | Doi | 10.1016/j.celrep.2024.114540 |
| Citation | Zhai S, et al. (2024) Ca(2+)-dependent phosphodiesterase 1 regulates the plasticity of striatal spiny projection neuron glutamatergic synapses. Cell Rep 43(8):114540 |
| abstractText | Long-term synaptic plasticity at glutamatergic synapses on striatal spiny projection neurons (SPNs) is central to learning goal-directed behaviors and habits. Our studies reveal that SPNs manifest a heterosynaptic, nitric oxide (NO)-dependent form of long-term postsynaptic depression of glutamatergic SPN synapses (NO-LTD) that is preferentially engaged at quiescent synapses. Plasticity is gated by Ca(2+) entry through Ca(V)1.3 Ca(2+) channels and phosphodiesterase 1 (PDE1) activation, which blunts intracellular cyclic guanosine monophosphate (cGMP) and NO signaling. Both experimental and simulation studies suggest that this Ca(2+)-dependent regulation of PDE1 activity allows for local regulation of dendritic cGMP signaling. In a mouse model of Parkinson disease (PD), NO-LTD is absent because of impaired interneuronal NO release; re-balancing intrastriatal neuromodulatory signaling restores NO release and NO-LTD. Taken together, these studies provide important insights into the mechanisms governing NO-LTD in SPNs and its role in psychomotor disorders such as PD. |
