Ca2+-dependent phosphodiesterase 1 regulates the plasticity of striatal spiny projection neuron glutamatergic synapses

Shenyu Zhai; Shintaro Otsuka; Jian Xu; Vernon R.J. Clarke; Tatiana Tkatch; David Wokosin; Zhong Xie; Asami Tanimura; Hitesh K. Agarwal; Graham C.R. Ellis-Davies; Anis Contractor; D. James Surmeier

doi:10.1016/j.celrep.2024.114540

Ca²⁺-dependent phosphodiesterase 1 regulates the plasticity of striatal spiny projection neuron glutamatergic synapses

Shenyu Zhai, Shintaro Otsuka, Jian Xu, Vernon R.J. Clarke, Tatiana Tkatch, David Wokosin, Zhong Xie, Asami Tanimura, Hitesh K. Agarwal, Graham C.R. Ellis-Davies, Anis Contractor, D. James Surmeier^*

^*Corresponding author af dette arbejde

Institut for Biomedicin - Fysiologi og Biofysik

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

1 Citationer (Scopus)

Abstract

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 Ca²⁺ entry through Ca_V1.3 Ca²⁺ channels and phosphodiesterase 1 (PDE1) activation, which blunts intracellular cyclic guanosine monophosphate (cGMP) and NO signaling. Both experimental and simulation studies suggest that this Ca²⁺-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.

Originalsprog	Engelsk
Artikelnummer	114540
Tidsskrift	Cell Reports
Vol/bind	43
Nummer	8
ISSN	2211-1247
DOI	https://doi.org/10.1016/j.celrep.2024.114540
Status	Udgivet - aug. 2024

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10.1016/j.celrep.2024.114540Licens: CC BY-NC

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Citationsformater

Zhai, S., Otsuka, S., Xu, J., Clarke, V. R. J., Tkatch, T., Wokosin, D., Xie, Z., Tanimura, A., Agarwal, H. K., Ellis-Davies, G. C. R., Contractor, A., & Surmeier, D. J. (2024). Ca²⁺-dependent phosphodiesterase 1 regulates the plasticity of striatal spiny projection neuron glutamatergic synapses. Cell Reports, 43(8), Artikel 114540. https://doi.org/10.1016/j.celrep.2024.114540

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title = "Ca2+-dependent phosphodiesterase 1 regulates the plasticity of striatal spiny projection neuron glutamatergic synapses",

abstract = "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 Ca2+ entry through CaV1.3 Ca2+ channels and phosphodiesterase 1 (PDE1) activation, which blunts intracellular cyclic guanosine monophosphate (cGMP) and NO signaling. Both experimental and simulation studies suggest that this Ca2+-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.",

keywords = "autism, cGMP, CP: Neuroscience, L-type Ca channel, low-threshold spiking interneuron, nitric oxide, Parkinson's disease, phosphodiesterase, spiny projection neuron, striatum, synaptic plasticity",

author = "Shenyu Zhai and Shintaro Otsuka and Jian Xu and Clarke, {Vernon R.J.} and Tatiana Tkatch and David Wokosin and Zhong Xie and Asami Tanimura and Agarwal, {Hitesh K.} and Ellis-Davies, {Graham C.R.} and Anis Contractor and Surmeier, {D. James}",

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doi = "10.1016/j.celrep.2024.114540",

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T1 - Ca2+-dependent phosphodiesterase 1 regulates the plasticity of striatal spiny projection neuron glutamatergic synapses

AU - Zhai, Shenyu

AU - Otsuka, Shintaro

AU - Xu, Jian

AU - Clarke, Vernon R.J.

AU - Tkatch, Tatiana

AU - Wokosin, David

AU - Xie, Zhong

AU - Tanimura, Asami

AU - Agarwal, Hitesh K.

AU - Ellis-Davies, Graham C.R.

AU - Contractor, Anis

AU - Surmeier, D. James

PY - 2024/8

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N2 - 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 Ca2+ entry through CaV1.3 Ca2+ channels and phosphodiesterase 1 (PDE1) activation, which blunts intracellular cyclic guanosine monophosphate (cGMP) and NO signaling. Both experimental and simulation studies suggest that this Ca2+-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.

AB - 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 Ca2+ entry through CaV1.3 Ca2+ channels and phosphodiesterase 1 (PDE1) activation, which blunts intracellular cyclic guanosine monophosphate (cGMP) and NO signaling. Both experimental and simulation studies suggest that this Ca2+-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.

KW - autism

KW - cGMP

KW - CP: Neuroscience

KW - L-type Ca channel

KW - low-threshold spiking interneuron

KW - nitric oxide

KW - Parkinson's disease

KW - phosphodiesterase

KW - spiny projection neuron

KW - striatum

KW - synaptic plasticity

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