Neuromodulation of excitatory synaptogenesis in striatal development

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Abstract

Dopamine is released in striatum during development and impacts the activity of Protein Kinase A (PKA) in striatal spiny projection neurons (SPNs). We examined whether dopaminergic neuromodulation regulates activity-dependent glutamatergic synapse formation in the developing striatum. Systemic in vivo treatment with Gα_s-coupled G-protein receptors (GPCRs) agonists enhanced excitatory synapses on direct pathway striatal spiny projection neurons (dSPNs), whereas rapid production of excitatory synapses on indirect pathway neurons (iSPNs) required the activation of Gα_s GPCRs in SPNs of both pathways. Nevertheless, in vitro Gα_s activation was sufficient to enhance spinogenesis induced by glutamate photolysis in both dSPNs and iSPNs, suggesting that iSPNs in intact neural circuits have additional requirements for rapid synaptic development. We evaluated the in vivo effects of enhanced glutamate release from corticostriatal axons and postsynaptic PKA and discovered a mechanism of developmental plasticity, wherein rapid synaptogenesis is promoted by the coordinated actions of glutamate and postsynaptic Gα_s-coupled receptors.

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Yevgenia Kozorovitskiy

Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Rui Peixoto

Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Wengang Wang

Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Arpiar Saunders

Department of Genetics, Harvard Medical School, Boston, United States

Competing interests
The authors declare that no competing interests exist.
Bernardo L Sabatini

Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States

For correspondence
bernardo_sabatini@hms.harvard.edu

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (03551) of Harvard Medical Area. The protocol was approved by the Harvard Medical Area Standing Committee on Animals. This institution has an approved Animal Welfare Assurance on file with the Office for Laboratory Animal Welfare. The Assurance number on file is A3431-01. All surgery was performed under isoflurane, and every effort was made to minimize suffering.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.