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

Cell Reports (Aug 2024)

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

Affiliations

Shenyu Zhai: Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Shintaro Otsuka: Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Jian Xu: Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Vernon R.J. Clarke: Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Tatiana Tkatch: Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
David Wokosin: Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Zhong Xie: Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Asami Tanimura: Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Hitesh K. Agarwal: Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA
Graham C.R. Ellis-Davies: Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA
Anis Contractor: Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
D. James Surmeier: Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Corresponding author

Journal volume & issue: Vol. 43, no. 8
p. 114540

Abstract

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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 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.

CP: Neuroscience

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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