Neuromodulation of excitatory synaptogenesis in striatal development.

Yevgenia Kozorovitskiy,Wengang Wang,Rui Peixoto,Arpiar Saunders,Bernardo L Sabatini

doi:10.7554/elife.10111

Yevgenia Kozorovitskiy, Wengang Wang + Show 3 more

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https://doi.org/10.7554/elife.10111

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Journal: eLife	Publication Date: Nov 9, 2015
Citations: 72	License type: CC BY 4.0

Affiliation: Northwestern University, Howard Hughes Medical Institute

Abstract

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.

Highlights

In the vertebrate basal ganglia, dopamine performs critical functions in motivated, goal-directed learning and behavior, transmitting signals related to rewarding stimuli and other salient experiences (Bromberg-Martin et al, 2010)
Comparisons of dendritic spine density and spontaneous miniature excitatory post-synaptic currents were made between slices prepared from mice injected 1 hr previously with saline or ligands for G-protein receptors (GPCRs) differentially expressed by direct pathway striatal spiny projection neurons (dSPNs) and iSPNs
Our data reveal that neuromodulation, through the activity of Protein Kinase A (PKA), enhances the probability of dendritic spine formation and lowers the amount of glutamate necessary to trigger spinogenesis in the developing striatum. These findings must be integrated into the context of basal ganglia circuitry, where inhibitory outputs of the direct and indirect pathways form functionally complementary loops that provide polysynaptic recurrent positive and negative feedback for excitatory striatal synaptogenesis (Kozorovitskiy et al, 2012)

Summary

Introduction

In the vertebrate basal ganglia, dopamine performs critical functions in motivated, goal-directed learning and behavior, transmitting signals related to rewarding stimuli and other salient experiences (Bromberg-Martin et al, 2010). Classical models of dopaminergic signaling in adult animals propose that the activity of dopamine-producing neurons encodes reward prediction errors and that released dopamine regulates the strength of corticostriatal excitatory glutamatergic inputs. This process is thought to favor the execution of a specific action that previously led to reward, at the expense of competing motor programs. Less is known about the function of dopamine in the postnatal development of basal ganglia, when goal-oriented motor programs are first expressed and activity-dependent synapse formation occurs in the striatum.

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