Neuronal glutamate transporters control reciprocal inhibition and gain modulation in D1 medium spiny neurons
- University at Albany, State University of New York, United States
Abstract
Understanding the function of glutamate transporters has broad implications for explaining how neurons integrate information and relay it through complex neuronal circuits. Most of what is currently known about glutamate transporters, specifically their ability to maintain glutamate homeostasis and limit glutamate diffusion away from the synaptic cleft, is based on studies of glial glutamate transporters. By contrast, little is known about the functional implications of neuronal glutamate transporters. The neuronal glutamate transporter EAAC1 is widely expressed throughout the brain, particularly in the striatum, the primary input nucleus of the basal ganglia, a region implicated with movement execution and reward. Here, we show that EAAC1 limits synaptic excitation onto a population of striatal medium spiny neurons identified for their expression of D1 dopamine receptors (D1-MSNs). In these cells, EAAC1 also contributes to strengthen lateral inhibition from other D1-MSNs. Together, these effects contribute to reduce the gain of the input-output relationship and increase the offset at increasing levels of synaptic inhibition in D1-MSNs. By reducing the sensitivity and dynamic range of action potential firing in D1-MSNs, EAAC1 limits the propensity of mice to rapidly switch between behaviors associated with different reward probabilities. Together, these findings shed light on some important molecular and cellular mechanisms implicated with behavior flexibility in mice.
Data availability
All primary data used in this work and complete statistical analyses for each figure have been deposited to the Open Science Framework (https://osf.io/dw5n7/).
Article and author information
Author details
Funding
National Science Foundation (IOS1655365)
- Annalisa Scimemi
National Science Foundation (IOS2011998)
- Annalisa Scimemi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Erin Calipari, Vanderbilt University, United States
Ethics
Animal experimentation: All experimental procedures were performed in accordance with protocols approved by the Institutional Animal Care and Use Committee at the State University of New York (SUNY) Albany and guidelines described in the National Institutes of Health's Guide for the Care and Use of Laboratory Animals.
Version history
- Received: July 13, 2022
- Preprint posted: July 14, 2022 (view preprint)
- Accepted: July 9, 2023
- Accepted Manuscript published: July 12, 2023 (version 1)
- Version of Record published: August 9, 2023 (version 2)
- Version of Record updated: August 17, 2023 (version 3)
Copyright
© 2023, Petroccione 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.
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Neuronal glutamate transporters control reciprocal inhibition and gain modulation in D1 medium spiny neurons
eLife 12:e81830.
https://doi.org/10.7554/eLife.81830
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