PBN-PVT projections modulate negative affective states in mice
- Shanghai Jiao Tong University School of Medicine, China
- Tongji University School of Medicine, China
- The First Affiliated Hospital of Guangzhou Medical University, China
Abstract
Long-lasting negative affections dampen enthusiasm for life, and dealing with negative affective states is essential for individual survival. The parabrachial nucleus (PBN) and thalamic paraventricular nucleus (PVT) are critical for modulating affective states in mice. However, the functional roles of PBN-PVT projections in modulating affective states remain elusive. Here, we show that PBN neurons send dense projection fibers to the PVT and form direct excitatory synapses with PVT neurons. Activation of the PBN-PVT pathway induces robust behaviors associated with negative affective states without affecting nociceptive behaviors. Inhibition of the PBN-PVT pathway reduces aversion-like and fear-like behaviors. Furthermore, the PVT neurons innervated by the PBN are activated by aversive stimulation, and activation of PBN-PVT projections enhances the neuronal activity of PVT neurons in response to the aversive stimulus. Consistently, activation of PVT neurons that received PBN-PVT projections induces anxiety-like behaviors. Thus, our study indicates that PBN-PVT projections modulate negative affective states in mice.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file. The behavioral data and imaging analysis results have been made available on Dryad Digital Repository (https://doi:10.5061/dryad.1rn8pk0w4). All MATLAB code has been deposited at: https://github.com/laizishangalali/Xiang/blob/main/zscore_KS_test.m and is publicly available.
-
PBN-PVT projections modulate negative affective states in miceDryad Digital Repository, doi:10.5061/dryad.1rn8pk0w4.
Article and author information
Author details
Funding
National Natural Science Foundation of China (31900717)
- Di Mu
China Association for Science and Technology (2019QNRC001)
- Di Mu
Shanghai Association for Science and Technology (19YF1438700)
- Di Mu
National Natural Science Foundation of China (31571086)
- Ling Zhang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiment procedures were approved by the Animal Care and Use Committee of Shanghai General Hospital (2019AW008).
Copyright
© 2022, Zhu 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
-
- 3,534
- views
-
- 566
- downloads
-
- 34
- 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)
PBN-PVT projections modulate negative affective states in mice
eLife 11:e68372.
https://doi.org/10.7554/eLife.68372
Further reading
-
- Neuroscience
Sequenced reactivations of hippocampal neurons called replays, concomitant with sharp-wave ripples in the local field potential, are critical for the consolidation of episodic memory, but whether replays depend on the brain’s reward or novelty signals is unknown. Here, we combined chemogenetic silencing of dopamine neurons in ventral tegmental area (VTA) and simultaneous electrophysiological recordings in dorsal hippocampal CA1, in freely behaving male rats experiencing changes to reward magnitude and environmental novelty. Surprisingly, VTA silencing did not prevent ripple increases where reward was increased, but caused dramatic, aberrant ripple increases where reward was unchanged. These increases were associated with increased reverse-ordered replays. On familiar tracks this effect disappeared, and ripples tracked reward prediction error (RPE), indicating that non-VTA reward signals were sufficient to direct replay. Our results reveal a novel dependence of hippocampal replay on dopamine, and a role for a VTA-independent RPE signal that is reliable only in familiar environments.
-
- Neuroscience
Active inference integrates perception, decision-making, and learning into a united theoretical framework, providing an efficient way to trade off exploration and exploitation by minimizing (expected) free energy. In this study, we asked how the brain represents values and uncertainties (novelty and variability), and resolves these uncertainties under the active inference framework in the exploration-exploitation trade-off. Twenty-five participants performed a contextual two-armed bandit task, with electroencephalogram (EEG) recordings. By comparing the model evidence for active inference and reinforcement learning models of choice behavior, we show that active inference better explains human decision-making under novelty and variability, which entails exploration or information seeking. The EEG sensor-level results show that the activity in the frontal, central, and parietal regions is associated with novelty, while the activity in the frontal and central brain regions is associated with variability. The EEG source-level results indicate that the expected free energy is encoded in the frontal pole and middle frontal gyrus and uncertainties are encoded in different brain regions but with overlap. Our study dissociates the expected free energy and uncertainties in active inference theory and their neural correlates, speaking to the construct validity of active inference in characterizing cognitive processes of human decisions. It provides behavioral and neural evidence of active inference in decision processes and insights into the neural mechanism of human decisions under uncertainties.
