TY - JOUR
T1 - Neuromodulation of excitatory synaptogenesis in striatal development
AU - Kozorovitskiy, Yevgenia
AU - Peixoto, Rui
AU - Wang, Wengang
AU - Saunders, Arpiar
AU - Sabatini, Bernardo L.
N1 - Funding Information:
The authors thank Rachel Pemberton for genotyping, Matt Banghart and Ruchir Shah for help with the SEAP assay, Lai Ding (Harvard NeuroDiscovery Center) for ImageJ macros, and all members of the Sabatini laboratory for helpful discussions. YK was supported by Leonard and Isabelle Goldenson Research Fellowship, the Nancy Lurie Marks Family Foundation, and William N. and Bernice E. Bumpus Foundation Innovation Award. RP was supported by the Alice and Joseph Brooks fellowship and the Nancy Lurie Marks Family Foundation. This work was supported by NS046579 and Howard Hughes Medical Institute (BLS).
Funding Information:
The authors thank Rachel Pemberton for genotyping, Matt Banghart and Ruchir Shah for help with the SEAP assay, Lai Ding (Harvard NeuroDiscovery Center) for ImageJ macros, and all members of the Sabatini laboratory for helpful discussions. YK was supported by Leonard and Isabelle Goldenson Research Fellowship, the Nancy Lurie Marks Family Foundation, and William N. and Bernice E. Bum-pus Foundation Innovation Award. RP was supported by the Alice and Joseph Brooks fellowship and the Nancy Lurie Marks Family Foundation. This work was supported by NS046579 and Howard Hughes Medical Institute (BLS).
Publisher Copyright:
© Kozorovitskiy et al.
PY - 2015/11/9
Y1 - 2015/11/9
N2 - Dopamine is released in the 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 Gαs-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 Gαs GPCRs in SPNs of both pathways. Nevertheless, in vitro Gαs 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 Gαs-coupled receptors.
AB - Dopamine is released in the 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 Gαs-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 Gαs GPCRs in SPNs of both pathways. Nevertheless, in vitro Gαs 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 Gαs-coupled receptors.
UR - http://www.scopus.com/inward/record.url?scp=84955318837&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84955318837&partnerID=8YFLogxK
U2 - 10.7554/eLife.10111.001
DO - 10.7554/eLife.10111.001
M3 - Article
C2 - 26551563
AN - SCOPUS:84955318837
SN - 2050-084X
VL - 4
JO - eLife
JF - eLife
IS - NOVEMBER2015
M1 - e10111
ER -