內耳由專司聽覺的耳蝸和專司平衡功能(包括凝視穩定,姿勢控制和空間導航)的前庭器官組成。這兩個系統司職不同功能,但具有相同的發育起源,并且都依賴機械敏感性毛細胞。與其他感覺系統(例如視覺,軀體感覺系統等)相比,我們對內耳神經元的分子多樣性及其對形態,生理和功能分化的影響所知甚少。博后期間我發現了聽覺系統的初級神經元可分為三種有顯著分子差異的亞型。這三種亞型表現出相應的形態與電生理特性。亞型的分化在出生后完成,并依賴聽覺系統的感官活動,為聽覺系統的研究提供了重要的理論基礎與全新的視角。
前庭系統司職平衡覺。其功能失衡導致的平衡障礙影響成年人口的15%,尤其是老年人。而與聽覺等其他感覺系統相比,我們對這神秘的“第六感”了解極其有限。前庭神經節神經元支配五個獨特的終末器官,以實現姿勢控制、空間導航和自主調節等各類功能。相應的,其形態與生理特性均有明顯差異。我們將從前庭神經節神經元的分子多樣性著手,利用單細胞測序、光遺傳與化學遺傳學、鈣成像、行為分析等方法闡釋前庭系統形態、生理與功能多樣性形成的分子機制。
The inner ear consists of the cochlea,
dedicated to hearing and the vestibular organs, dedicated to balance functions,
including gaze stabilization, postural control and spatial navigation. These
two systems share the same developmental origin and mechanosensitive hair cells
are used by both but to achieve distinct functions. Comparing to other sensory
systems (e.g. visual, somatosensory), the molecular heterogeneity of neurons in
the inner ear and how they contribute to the morphological, physiological and
functional diversity have not been well-established and appreciated. I demonstrated,
during my postdoc, that type I SGNs consist of three molecularly distinct
subtypes (named type Ia, type Ib and type Ic), which exhibit anatomical and
physiological differences. Specification of the subtypes is finished
postnatally in an activity dependent manner. These results can provide new
angles for the mechanistic understanding of sensory coding in the auditory
system.
The vestibular system is critical to our sense of balance and spatial orientation.
Malfunctions of the system lead to balance disorders that can affect 15 percent
of the adult population, especially the elderly. Comparing to other sensory
systems, such as the auditory system, this second part of the inner ear has
drawn less public or scientific attention. Vestibular ganglion neurons (VGNs)
innervate five distinctive end organs to carry out diverse functions ranging
from gaze stabilization and spatial navigation to cognitive functions and
autonomic regulations. Accordingly, VGNs exhibit pronounced anatomical and
physiological diversity. We plan to begin the characterization of the
vestibular circuitries with the molecular and cellular diversity of the
vestibular ganglion neurons.
發表文章
1. Sun S, Siebald C, Mueller U. (2021) Subtype Maturation of Spiral Ganglion Neurons. Current Opinion in Otolaryngology &
Head and Neck Surgery 29(5):391-399.
2. Sun S*, Babola T*, Palermo A*, So K, Nguyen M, Su S,
Palermo A, Bergles D, Burns J, Mueller U. (2018) Hair Cell Mechanotransduction
Regulates Spontaneous Activity and Spiral Ganglion Subtype Specification in the
Auditory System. Cell 174(5):1246-1632. *contributed equally
to this work.
Highlighted/previewed in:
Whalley, Nature Review Neuroscience.
19,579 (2018)
Kandler, Neuron. 2018.07.043
Fekete, F1000.
3. Sun S*, Xu Q*, Guo C, Guan Y,
Liu Q and Dong X. (2017) Leaky gate model: intensity-dependent coding of pain
and itch in the spinal cord. Neuron, 93(4):840-853. *contributed equally
to this work.
Highlighted/previewed in:
Pereira and Lerner, Neuron. 2017.02.016
4. Sun S, Dong X. (2016) Trp channels and itch. Seminars in immunopathology 38(3), 293-307.
5. Reddy
VB*, Sun S*, Azimi E, Elmariah SB,
Dong X, Lerner EA. (2015) Redefining the concept of protease-activated
receptors: cathepsin S evokes itch via activation of Mrgprs. Nature communications, 6:7864. *contributed equally to this work.
6. Li Z, Tseng P.-Y, Tiwari
V, Xu Q, He S.-Q, Wang Y, Zheng Q, Han L, Wu Z, Blobaum A.L, Cui Y, Tiwari V, Sun
S, Cheng Y, Huang-Lionnet J.H.Y, Geng Y, Xiao B, Peng J, Hopkins C, Raja
S.N, Guan Y, Dong X. (2017) Targeting human Mas-related G protein-coupled
receptor X1 to inhibit persistent pain. Proc. Natl. Acad. Sci, 114(10): E1996-2005.
7. Kim YS, Chu Y, Han L, Li M, Li Z, Lavinka PC, Sun S, Tang Z, Park K, Caterina MJ, Ren
K, Dubner R, Wei F, Dong X. (2014) Central terminal sensitization of TRPV1 by
descending serotonergic facilitation modulates chronic pain. Neuron, 81(4):873-87.
8. Liu Q, Sikand P, Ma C, Tang Z, Han L, Li Z, Sun S, LaMotte RH, Dong X. (2012)
Mechanisms of itch evoked by β-alanine. J
Neurosci.3509-12.
Invited Book Chapters
Itch and Pain: Similarities,
Interactions and Differences
Chapter: Interneurons and Their Roles
in Itch and Pain, Author: Shuohao Sun
International Association for the Study
of Pain Press (2020年7月)