Neuromodulation of excitatory synaptogenesis in striatal development
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 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.
Article and author information
Author details
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.
Copyright
© 2015, Kozorovitskiy et al.
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.
Metrics
-
- 3,957
- views
-
- 901
- downloads
-
- 61
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
Recognizing and responding to threat cues is essential to survival. Freezing is a predominant threat behavior in rats. We have recently shown that a threat cue can organize diverse behaviors beyond freezing, including locomotion (Chu et al., 2024). However, that experimental design was complex, required many sessions, and had rats receive many foot shock presentations. Moreover, the findings were descriptive. Here, we gave female and male Long Evans rats cue light illumination paired or unpaired with foot shock (8 total) in a conditioned suppression setting, using a range of shock intensities (0.15, 0.25, 0.35, or 0.50 mA). We found that conditioned suppression was only observed at higher foot shock intensities (0.35 mA and 0.50 mA). We constructed comprehensive temporal ethograms by scoring 22,272 frames across 12 behavior categories in 200-ms intervals around cue light illumination. The 0.50 mA and 0.35 mA shock-paired visual cues suppressed reward seeking, rearing, and scaling, as well as light-directed rearing and light-directed scaling. The shock-paired visual cue further elicited locomotion and freezing. Linear discriminant analyses showed that ethogram data could accurately classify rats into paired and unpaired groups. Using complete ethogram data produced superior classification compared to behavior subsets, including an Immobility subset featuring freezing. The results demonstrate diverse threat behaviors – in a short and simple procedure – containing sufficient information to distinguish the visual fear conditioning status of individual rats.
-
- Neuroscience
The neural noise hypothesis of dyslexia posits an imbalance between excitatory and inhibitory (E/I) brain activity as an underlying mechanism of reading difficulties. This study provides the first direct test of this hypothesis using both electroencephalography (EEG) power spectrum measures in 120 Polish adolescents and young adults (60 with dyslexia, 60 controls) and glutamate (Glu) and gamma-aminobutyric acid (GABA) concentrations from magnetic resonance spectroscopy (MRS) at 7T MRI scanner in half of the sample. Our results, supported by Bayesian statistics, show no evidence of E/I balance differences between groups, challenging the hypothesis that cortical hyperexcitability underlies dyslexia. These findings suggest that alternative mechanisms must be explored and highlight the need for further research into the E/I balance and its role in neurodevelopmental disorders.