Long-term two-photon imaging of spinal cord in freely behaving mice

Ju, Furong; Jian, Wenling; Han, Yaning; Huang, Tianwen; Liu, Zhiheng; Cai, Shengyuan; Liu, Nan; Wang, Liping; Wei, Pengfei

doi:10.1101/2022.01.09.475306

Cited by 6 publications

(3 citation statements)

References 48 publications

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“…Moreover, the nature of neural transmission also suggests that these endogenous activities probably occur at second or millisecond scales. Thus, a matching ability to readout projection-specific DRG activities in vivo would be required to identify the triggering signals, for example, using emerging long-term DRG calcium imaging techniques 47,48 .…”

Section: Discussionmentioning

confidence: 99%

The role of somatosensory innervation of adipose tissues

Wang

Leung

Zhang

et al. 2022

Nature

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Adipose tissues communicate with the central nervous system to maintain whole-body energy homeostasis. The mainstream view is that circulating hormones secreted by the fat convey the metabolic state to the brain, which integrates peripheral information and regulates adipocyte function through noradrenergic sympathetic output1. Moreover, somatosensory neurons of the dorsal root ganglia innervate adipose tissue2. However, the lack of genetic tools to selectively target these neurons has limited understanding of their physiological importance. Here we developed viral, genetic and imaging strategies to manipulate sensory nerves in an organ-specific manner in mice. This enabled us to visualize the entire axonal projection of dorsal root ganglia from the soma to subcutaneous adipocytes, establishing the anatomical underpinnings of adipose sensory innervation. Functionally, selective sensory ablation in adipose tissue enhanced the lipogenic and thermogenetic transcriptional programs, resulting in an enlarged fat pad, enrichment of beige adipocytes and elevated body temperature under thermoneutral conditions. The sensory-ablation-induced phenotypes required intact sympathetic function. We postulate that beige-fat-innervating sensory neurons modulate adipocyte function by acting as a brake on the sympathetic system. These results reveal an important role of the innervation by dorsal root ganglia of adipose tissues, and could enable future studies to examine the role of sensory innervation of disparate interoceptive systems.

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Section: Discussionmentioning

confidence: 99%

The role of somatosensory innervation of adipose tissues

Wang

Leung

Zhang

et al. 2022

Nature

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“…Repeated imaging through spinal cord-implanted microprism is feasible over at least four weeks. This recording period may enable the study of prolonged structural and functional biological processes, such as disease-or treatment-related dynamics (e.g., amyotrophic lateral or multiple sclerosis progression, transplanted neural stem cell integration, neuropathic pain) 9,10,28,29 . Optical recordings from the spinal ventral horn might be feasible with custom microoptics.…”

Section: Discussionmentioning

confidence: 99%

Multiplex translaminar imaging in the spinal cord of behaving mice

et al. 2023

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While the spinal cord is known to play critical roles in sensorimotor processing, including pain-related signaling, corresponding activity patterns in genetically defined cell types across spinal laminae have remained challenging to investigate. Calcium imaging has enabled cellular activity measurements in behaving rodents but is currently limited to superficial regions. Here, using chronically implanted microprisms, we imaged sensory and motor-evoked activity in regions and at speeds inaccessible by other high-resolution imaging techniques. To enable translaminar imaging in freely behaving animals through implanted microprisms, we additionally developed wearable microscopes with custom-compound microlenses. This system addresses multiple challenges of previous wearable microscopes, including their limited working distance, resolution, contrast, and achromatic range. Using this system, we show that dorsal horn astrocytes in behaving mice show sensorimotor program-dependent and lamina-specific calcium excitation. Additionally, we show that tachykinin precursor 1 (Tac1)-expressing neurons exhibit translaminar activity to acute mechanical pain but not locomotion.

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“…For example, spinal cord flexibility during natural locomotion, exacerbated by breathing, produces motion artifacts in imaging data and hinders quantitative analysis. Not surprisingly, few studies have recorded spinal cord neural activity, long-term in awake animals (Cheng et al, 2016;Sekiguchi et al, 2016;Ju et al, 2022;Shekhtmeyster et al, 2023).…”

Section: Main Textmentioning

confidence: 99%

Long-term optical imaging of the spinal cord in awake, behaving animals

Ahanonu

Crowther

Kania

et al. 2023

Preprint

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Advances in optical imaging approaches and fluorescent biosensors have enabled an understanding of the spatiotemporal and long-term neural dynamics in the brain of awake animals. However, methodological difficulties and the persistence of post-laminectomy fibrosis have greatly limited similar advances in the spinal cord. To overcome these technical obstacles, we combinedin vivoapplication of fluoropolymer membranes that inhibit fibrosis; a redesigned, cost-effective implantable spinal imaging chamber; and improved motion correction methods that together permit imaging of the spinal cord in awake, behaving mice, for months to over a year. We also demonstrate a robust ability to monitor axons, identify a spinal cord somatotopic map, conduct Ca2+imaging of neural dynamics in behaving animals responding to pain-provoking stimuli, and observe persistent microglial changes after nerve injury. The ability to couple neural activity and behavior at the spinal cord level will drive insights not previously possible at a key location for somatosensory transmission to the brain.

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Long-term two-photon imaging of spinal cord in freely behaving mice

Cited by 6 publications

References 48 publications

The role of somatosensory innervation of adipose tissues

The role of somatosensory innervation of adipose tissues

Multiplex translaminar imaging in the spinal cord of behaving mice

Long-term optical imaging of the spinal cord in awake, behaving animals

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