Whole-Brain Connectome of GABAergic Neurons in the Mouse Zona Incerta

Yang, Yang; Jiang, Tao; Jia, Xueyan; Yuan, Jing; Li, Xiangning; Gong, Hui

doi:10.1007/s12264-022-00930-w

Cited by 27 publications

(30 citation statements)

References 47 publications

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“…First, to determine the connections between ZI and PVT, we injected the retrograde tracer 594 retroBeads into PVT of C57BL/6J mice ( Figure 1 A). We found that the retrograde labeled neurons mainly occupied the ZIR and were rarely observed in the other parts of ZI ( Figure 1 C,D), which is consistent with previous study [ 19 ].…”

Section: Resultssupporting

confidence: 92%

“…Since the PVT is lacks of the GABAergic inhibitory neurons, the modulation of PVT function relies on inhibitory afferents for excitation and inhibition balance in neurotransmission [ 18 ]. It is noted that ZIR is one of GABAergic source to PVT [ 19 ], recent studies demonstrated that the GABAergic ZIR neurons project to PVT neurons and contribute to conditioned feeding behavior [ 6 , 20 ]. However, the roles of the ZIR–PVT pathway in nociceptive neurotransmission have not been fully addressed.…”

Section: Introductionmentioning

confidence: 99%

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Projections from the Rostral Zona Incerta to the Thalamic Paraventricular Nucleus Mediate Nociceptive Neurotransmission in Mice

Chen

et al. 2023

Metabolites

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Zona incerta (ZI) is an integrative subthalamic region in nociceptive neurotransmission. Previous studies demonstrated that the rostral ZI (ZIR) is an important gamma–aminobutyric acid-ergic (GABAergic) source to the thalamic paraventricular nucleus (PVT), but whether the ZIR–PVT pathway participates in nociceptive modulation is still unclear. Therefore, our investigation utilized anatomical tracing, fiber photometry, chemogenetic, optogenetic and local pharmacological approaches to investigate the roles of the ZIRGABA+–PVT pathway in nociceptive neurotransmission in mice. We found that projections from the GABAergic neurons in ZIR to PVT were involved in nociceptive neurotransmission. Furthermore, chemogenetic and optogenetic activation of the ZIRGABA+–PVT pathway alleviates pain, whereas inhibiting the activities of the ZIRGABA+-PVT circuit induces mechanical hypersensitivity and partial heat hyperalgesia. Importantly, in vivo pharmacology combined with optogenetics revealed that the GABA-A receptor (GABAAR) is crucial for GABAergic inhibition from ZIR to PVT. Our data suggest that the ZIRGABA+–PVT pathway acts through GABAAR-expressing glutamatergic neurons in PVT mediates nociceptive neurotransmission.

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Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Projections from the Rostral Zona Incerta to the Thalamic Paraventricular Nucleus Mediate Nociceptive Neurotransmission in Mice

Chen

et al. 2023

Metabolites

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“…In a previous mapping study of input and output connections of ZI GABAergic neurons, rabies virus-enabled monosynaptic retrograde tracing has labeled many ZI-projecting cells in the SNpc and SNpr. 67 Given the fact that SN DA neurons are mainly located in the SNpc, although further cellular phenotyping of those ZI-projecting SNpc cells is lacking in that study, we would interpret that the observed ZIprojecting SNpc neurons in Yang et al (2022) are likely to be dopaminergic. In addition, previous study has suggested the existence of D1R and D2R modulation in the ZI and shown that DA injected into the medial ZI exerts a weak inhibitory effect on food intake through dominant D2R over D1R modulation.…”

Section: Discussionmentioning

confidence: 83%

A nigroincertal projection mediates aversion and enhances coping responses to potential threat

Ho,

Hsiao,

Chiu

et al. 2023

The FASEB Journal

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Recent studies have shown that the non‐DA neurons in the ventral tegmental area (VTA) and substantia nigra (SN) not only modulate motivational behaviors but also regulate defensive behaviors. While zona incerta (ZI) is a threat‐responsive substrate and receives innervations from the ventral midbrain, the function of the ventral midbrain‐to‐ZI connection remains poorly defined. Here, we demonstrate that the ZI receives heterogenous innervations from the ventral midbrain. By utilizing a retrograde AAV preferentially labeling non‐DA neurons in the ventral midbrain, we found that ZI‐projecting non‐DA cells in the ventral midbrain are activated by restraint stress. We focused on the SN and found that SN‐to‐ZI GABAergic input is engaged by a predatory odor. Sustained pan‐neuronal SN‐to‐ZI activation results in aversion and enhances defensive behaviors, likely through a disinhibition mechanism to recruit downstream brain regions that regulate defensive behaviors. Collectively, our results reveal a novel role of nigroincertal projection in mediating negative valence and regulating defensive behaviors.

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“…As the most complex organ, the brain contains trillion-level neurons, glia and other types of cells with complex connectivity. It implies that the functional states of different cells vary across distant regions, requiring large-scale investigations 5 , 6 . The whole-organ mapping efforts are building the foundations for the understanding of tissue architecture at the mesoscopic level 7 .…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional mapping in multi-samples with large-scale imaging and multiplexed post staining

Chen

Liu²,

Li³

et al. 2023

Commun Biol

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Dissection of the anatomical information at the single-cell level is crucial for understanding the organization rule and pathological mechanism of biological tissues. Mapping the whole organ in numerous groups with multiple conditions brings the challenges in imaging and analysis. Here, we describe an approach, named array fluorescent micro-optical sectioning tomography (array-fMOST), to identify the three-dimensional information at single-cell resolution from multi-samples. The pipeline contains array embedding, large-scale imaging, post-imaging staining and data analysis, which could image over 24 mouse brains simultaneously and collect the slices for further analysis. With transgenic mice, we acquired the distribution information of neuropeptide somatostatin neurons during natural aging and compared the changes in the microenvironments by multi-component labeling of serial sections with precise co-registration of serial datasets quantitatively. With viral labeling, we also analyzed the input circuits of the medial prefrontal cortex in the whole brain of Alzheimer’s disease and autism model mice. This pipeline is highly scalable to be applied to anatomical alterations screening and identification. It provides new opportunities for combining multi-sample whole-organ imaging and molecular phenotypes identification analysis together. Such integrated high-dimensional information acquisition method may accelerate our understanding of pathogenesis and progression of disease in situ at multiple levels.

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Whole-Brain Connectome of GABAergic Neurons in the Mouse Zona Incerta

Cited by 27 publications

References 47 publications

Projections from the Rostral Zona Incerta to the Thalamic Paraventricular Nucleus Mediate Nociceptive Neurotransmission in Mice

Projections from the Rostral Zona Incerta to the Thalamic Paraventricular Nucleus Mediate Nociceptive Neurotransmission in Mice

A nigroincertal projection mediates aversion and enhances coping responses to potential threat

Three-dimensional mapping in multi-samples with large-scale imaging and multiplexed post staining

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