Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium
- Oregon Health and Science University, United States
- Oregon Health & Science University, United States
- United States Department of Veterans Affairs, United States
- Massachusetts Institute of Technology, United States
Abstract
D2 autoreceptors regulate dopamine release throughout the brain. Two isoforms of the D2 receptor, D2S and D2L, are expressed in midbrain dopamine neurons. Differential roles of these isoforms as autoreceptors are poorly understood. By virally expressing the isoforms in dopamine neurons of D2 receptor knockout mice, this study assessed the calcium-dependence and drug-induced plasticity of D2S and D2L receptor-dependent GIRK currents. The results reveal that D2S, but not D2L receptors, exhibited calcium-dependent desensitization similar to that exhibited by endogenous autoreceptors. Two pathways of calcium signaling that regulated D2 autoreceptor-dependent GIRK signaling were identified, which distinctly affected desensitization and the magnitude of D2S and D2L receptor-dependent GIRK currents. Previous in vivo cocaine exposure removed calcium-dependent D2 autoreceptor desensitization in wild type, but not D2S-only mice. Thus, expression of D2S as the exclusive autoreceptor was insufficient for cocaine-induced plasticity, implying a functional role for the co-expression of D2S and D2L autoreceptors.
Article and author information
Author details
Ethics
Animal experimentation: All studies were conducted in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and were approved by the Institutional Animal Care and Use Committees at the VA Portland Health Care System (#2577-12) and Oregon Health & Science University (IS01394).
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Metrics
-
- 2,944
- views
-
- 555
- downloads
-
- 36
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
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)
Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium
eLife 4:e09358.
https://doi.org/10.7554/eLife.09358
Further reading
-
- Neuroscience
This work proposes µGUIDE: a general Bayesian framework to estimate posterior distributions of tissue microstructure parameters from any given biophysical model or signal representation, with exemplar demonstration in diffusion-weighted magnetic resonance imaging. Harnessing a new deep learning architecture for automatic signal feature selection combined with simulation-based inference and efficient sampling of the posterior distributions, µGUIDE bypasses the high computational and time cost of conventional Bayesian approaches and does not rely on acquisition constraints to define model-specific summary statistics. The obtained posterior distributions allow to highlight degeneracies present in the model definition and quantify the uncertainty and ambiguity of the estimated parameters.
-
- Computational and Systems Biology
- Neuroscience
The basolateral amygdala (BLA) is a key site where fear learning takes place through synaptic plasticity. Rodent research shows prominent low theta (~3–6 Hz), high theta (~6–12 Hz), and gamma (>30 Hz) rhythms in the BLA local field potential recordings. However, it is not understood what role these rhythms play in supporting the plasticity. Here, we create a biophysically detailed model of the BLA circuit to show that several classes of interneurons (PV, SOM, and VIP) in the BLA can be critically involved in producing the rhythms; these rhythms promote the formation of a dedicated fear circuit shaped through spike-timing-dependent plasticity. Each class of interneurons is necessary for the plasticity. We find that the low theta rhythm is a biomarker of successful fear conditioning. The model makes use of interneurons commonly found in the cortex and, hence, may apply to a wide variety of associative learning situations.
