Ca 2+ -dependent phosphodiesterase 1 regulates the plasticity of striatal spiny projection neuron glutamatergic synapses

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 glutamatergi...

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Published in:Cell reports (Cambridge) 2024-08, Vol.43 (8), p.114540
Main Authors: Zhai, Shenyu, Otsuka, Shintaro, Xu, Jian, Clarke, Vernon R J, Tkatch, Tatiana, Wokosin, David, Xie, Zhong, Tanimura, Asami, Agarwal, Hitesh K, Ellis-Davies, Graham C R, Contractor, Anis, Surmeier, D James
Format: Article
Language:English
Subjects:
Animals
Calcium - metabolism
Corpus Striatum - metabolism
Cyclic GMP - metabolism
Cyclic Nucleotide Phosphodiesterases, Type 1 - metabolism
Glutamic Acid - metabolism
Long-Term Synaptic Depression - physiology
Male
Mice
Mice, Inbred C57BL
Neuronal Plasticity - physiology
Neurons - metabolism
Nitric Oxide - metabolism
Synapses - metabolism
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Summary: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 entry through Ca 1.3 Ca 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 -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.
ISSN:2211-1247