An extended amygdala-midbrain circuit controlling cocaine withdrawal-induced anxiety and reinstatement

Guo, Ten-Huei; Hui, May; Macchia, Desiree; Derdeyn, Pieter; Rogers, Alexandra; Hubbard, Elizabeth; Liu, Chengfeng; Vasquez, Jose J; Taniguchi, Lara; Bartas, Katrina; Carroll, Sean; Beier, Kevin T.

doi:10.1016/j.celrep.2022.110775

Cited by 23 publications

(34 citation statements)

References 74 publications

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“…Furthermore, the current study’s correlation analysis showed a significant negative correlation between the NBM-midbrain connectivity and the SAS score. This correlation result was supported by recent studies, which have reported that the midbrain has been critically implicated in anxiety-like behaviors ( 55 , 56 ). The negative correlation in the current study may indicate that the increased NBM-midbrain connectivity reflects a compensatory mechanism to combat the anxiety problem in the ID patient.…”

Section: Discussionsupporting

confidence: 80%

Distinct alterations of functional connectivity of the basal forebrain subregions in insomnia disorder

Jiang

Feng²,

Li³

et al. 2022

Front. Psychiatry

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BackgroundCholinergic basal forebrain (BF) plays an important role in sleep-wake regulation and is implicated in cortical arousal and activation. However, less is known currently regarding the abnormal BF-related neuronal circuit in human patients with insomnia disorder (ID). In this study, we aimed to explore alterations of functional connectivity (FC) in subregions of the BF and the relationships between FC alterations and sleep and mood measures in ID.Materials and methodsOne hundred and two ID patients and ninety-six healthy controls (HC) were included in this study. Each subject underwent both resting-state fMRI and high-resolution anatomical scanning. All participants completed the sleep and mood questionnaires in ID patients. Voxel-based resting-state FC in each BF subregion (Ch_123 and Ch_4) were computed. For the voxel-wise FC differences between groups, a two-sample t-test was performed on the individual maps in a voxel-by-voxel manner. To examine linear relationships with sleep and mood measures, Pearson correlations were calculated between FC alterations and sleep and mood measures, respectively.ResultsThe ID group showed significantly decreased FC between the medial superior frontal gyrus and Ch_123 compared to HC. However, increased FC between the midbrain and Ch_4 was found in ID based on the voxel-wise analysis. The correlation analysis only revealed that the altered FC between the midbrain with Ch_4 was significantly negatively correlated with the self-rating anxiety scale.ConclusionOur findings of decreased FC between Ch_123 and medial superior frontal gyrus and increased FC between midbrain and Ch4 suggest distinct roles of subregions of BF underlying the neurobiology of ID.

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Section: Discussionsupporting

confidence: 80%

Distinct alterations of functional connectivity of the basal forebrain subregions in insomnia disorder

Jiang

Feng²,

Li³

et al. 2022

Front. Psychiatry

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“…This data suggests that the BNST-VTA connection is required for stress-induced reinstatement. Furthermore, the fact that BNST GABA ≫ midbrain ≫ Amygdala pathway regulates cocaine-induced anxiety highlights the significance of cell type- and projection-specific investigations in translational studies (Tian et al, 2022 ). Our analysis of the electrophysiological heterogeneity of the VTA-projecting BNST neurons helps expand the foundation to study their cell-type specific role for designing targeted therapeutics for addiction and anxiety.…”

Section: Discussionmentioning

confidence: 99%

Electrophysiologically distinct bed nucleus of the stria terminalis projections to the ventral tegmental area in mice

Miura

Shanley²,

Urbaez³

et al. 2023

Front. Neural Circuits

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The bed nucleus of the stria terminalis (BNST) is a highly heterogeneous limbic forebrain structure that serves as a relay connecting autonomic, neuroendocrine and behavioral function. It can be divided into over 16 individual subregions with distinct neuronal subpopulations based on receptors, transmitters, and neuropeptides. Specifically, the BNST projection to the ventral tegmental area (VTA), the dopamine hub of the brain, has been shown to have a crucial role in the stress response. However, in mice there is a lack of unbiased data on the functional diversity of this sub-population which serves as an upstream input to the VTA. The dopaminergic neurons in the VTA modify their ion channel activity and intrinsic membrane properties to adapt to stress in part from inputs from BNST projections. Therefore, we aimed to perform a multi-component characterization of the functional diversity of the BNST-VTA pathway. We studied the passive and active electrophysiological properties of virally identified population of BNST neurons that project to the VTA. We used a comprehensive series of in vitro recordings of electrophysiological variables and performed hierarchical clustering to determine the functional diversity of the projection neurons in the BNST-VTA pathway. Our study revealed four subpopulations in the BNST-VTA pathway, all of which differ in their activation profiles and likely have distinct inputs and function in the VTA. Our results will help resolve the discord in interpretation of the various roles of this electrophysiologically diverse projection and builds a foundation for understanding how the different neuronal types integrate signals.

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“…For example, we do not know if RABV labels neurons in proportion to particular properties of connections such as synaptic strength or release probability. While we have obtained some evidence that RABV labeling is sensitive to the relative activity of input populations ( Beier et al, 2017 ; Tian et al, 2022 ), we only assessed how RABV labeled particular inputs before and after an experience. How input activity more generally may affect RABV labeling is not known.…”

Section: Discussionmentioning

confidence: 99%

Modified viral-genetic mapping reveals local and global connectivity relationships of ventral tegmental area dopamine cells

Beier

2022

eLife

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Dopamine cells in the ventral tegmental area (VTADA) are critical for a variety of motivated behaviors. These cells receive synaptic inputs from over 100 anatomically-defined brain regions, which enables control from a distributed set of inputs across the brain. Extensive efforts have been made to map inputs to VTA cells based on neurochemical phenotype and output site. However, all of these studies have the same fundamental limitation that inputs local to the VTA cannot be properly assessed due to non-Cre-dependent uptake of EnvA-pseudotyped virus. Therefore, the quantitative contribution of local inputs to the VTA, including GABAergic, DAergic, and serotonergic, is not known. Here, I used a modified viral-genetic strategy that enables examination of both local as well as long-range inputs to VTADA cells in mice. I found that nearly half of the total inputs to VTADA cells are located locally, revealing a substantial portion of inputs that have been missed by previous analyses. The majority of inhibition to VTADA cells arises from the substantia nigra pars reticulata, with large contributions from the VTA and the substantia nigra pars compacta. In addition to receiving inputs from VTAGABA neurons, DA neurons are connected with other DA neurons within the VTA as well as the nearby retrorubal field. Lastly, I show that VTADA neurons receive inputs from distributed serotonergic neurons throughout the midbrain and hindbrain, with the majority arising from the dorsal raphe. My study highlights the importance of using the appropriate combination of viral-genetic reagents to unmask the complexity of connectivity relationships to defined cells in the brain.

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An extended amygdala-midbrain circuit controlling cocaine withdrawal-induced anxiety and reinstatement

Cited by 23 publications

References 74 publications

Distinct alterations of functional connectivity of the basal forebrain subregions in insomnia disorder

Distinct alterations of functional connectivity of the basal forebrain subregions in insomnia disorder

Electrophysiologically distinct bed nucleus of the stria terminalis projections to the ventral tegmental area in mice

Modified viral-genetic mapping reveals local and global connectivity relationships of ventral tegmental area dopamine cells

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