Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation
- Fudan Univeristy, China
- Fudan University, China
Abstract
One reported mechanism for morphine activation of dopamine (DA) neurons of the ventral tegmental area (VTA) is the disinhibition model of VTA-DA neurons. Morphine inhibits GABA inhibitory neurons, which shifts the balance between inhibitory and excitatory input to VTA-DA neurons in favor of excitation and then leads to VTA-DA neuron excitation. However, it is not known whether morphine has an additional strengthening effect on excitatory input. Our results suggest that glutamatergic input to VTA-DA neurons is inhibited by GABAergic interneurons via GABAB receptors and that morphine promotes presynaptic glutamate release by removing this inhibition. We also studied the contribution of the morphine-induced disinhibitory effect on the presynaptic glutamate release to the overall excitatory effect of morphine on VTA-DA neurons and related behavior. Our results suggest that the disinhibitory action of morphine on presynaptic glutamate release might be the main mechanism for morphine-induced increase in VTA-DA neuron firing and related behaviors.
Article and author information
Author details
Reviewing Editor
- Wolfram Schultz, University of Cambridge, United Kingdom
Ethics
Animal experimentation: All experimental procedures conformed to Fudan University as well as international guidelines on the ethical use of animals and all efforts were made to minimize the number of animals used and their suffering.
Version history
- Received: June 8, 2015
- Accepted: July 24, 2015
- Accepted Manuscript published: July 24, 2015 (version 1)
- Version of Record published: August 17, 2015 (version 2)
Copyright
© 2015, Chen 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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Morphine disinhibits glutamatergic input to VTA dopamine neurons and promotes dopamine neuron excitation
eLife 4:e09275.
https://doi.org/10.7554/eLife.09275
Further reading
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- Neuroscience
Probing memory of a complex visual image within a few hundred milliseconds after its disappearance reveals significantly greater fidelity of recall than if the probe is delayed by as little as a second. Classically interpreted, the former taps into a detailed but rapidly decaying visual sensory or ‘iconic’ memory (IM), while the latter relies on capacity-limited but comparatively stable visual working memory (VWM). While iconic decay and VWM capacity have been extensively studied independently, currently no single framework quantitatively accounts for the dynamics of memory fidelity over these time scales. Here, we extend a stationary neural population model of VWM with a temporal dimension, incorporating rapid sensory-driven accumulation of activity encoding each visual feature in memory, and a slower accumulation of internal error that causes memorized features to randomly drift over time. Instead of facilitating read-out from an independent sensory store, an early cue benefits recall by lifting the effective limit on VWM signal strength imposed when multiple items compete for representation, allowing memory for the cued item to be supplemented with information from the decaying sensory trace. Empirical measurements of human recall dynamics validate these predictions while excluding alternative model architectures. A key conclusion is that differences in capacity classically thought to distinguish IM and VWM are in fact contingent upon a single resource-limited WM store.
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- Neuroscience
Our ability to recall details from a remembered image depends on a single mechanism that is engaged from the very moment the image disappears from view.
