Skip to main content

Advertisement

SpringerLink
Log in

A Non-canonical Excitatory PV RGC–PV SC Visual Pathway for Mediating the Looming-evoked Innate Defensive Response

  • Original Article
  • Published:
Neuroscience Bulletin Aims and scope Submit manuscript

Abstract

Parvalbumin-positive retinal ganglion cells (PV+ RGCs) are an essential subset of RGCs found in various species. However, their role in transmitting visual information remains unclear. Here, we characterized PV+ RGCs in the retina and explored the functions of the PV+ RGC-mediated visual pathway. By applying multiple viral tracing strategies, we investigated the downstream of PV+ RGCs across the whole brain. Interestingly, we found that the PV+ RGCs provided direct monosynaptic input to PV+ excitatory neurons in the superficial layers of the superior colliculus (SC). Ablation or suppression of SC-projecting PV+ RGCs abolished or severely impaired the flight response to looming visual stimuli in mice without affecting visual acuity. Furthermore, using transcriptome expression profiling of individual cells and immunofluorescence colocalization for RGCs, we found that PV+ RGCs are predominant glutamatergic neurons. Thus, our findings indicate the critical role of PV+ RGCs in an innate defensive response and suggest a non-canonical subcortical visual pathway from excitatory PV+ RGCs to PV+ SC neurons that regulates looming visual stimuli. These results provide a potential target for intervening and treating diseases related to this circuit, such as schizophrenia and autism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Gonchar Y, Wang Q, Burkhalter A. Multiple distinct subtypes of GABAergic neurons in mouse visual cortex identified by triple immunostaining. Front Neuroanat 2007, 1: 3.

    PubMed  Google Scholar 

  2. Nahar L, Delacroix BM, Nam HW. The role of parvalbumin interneurons in neurotransmitter balance and neurological disease. Front Psychiatry 2021, 12: 679960.

    PubMed  PubMed Central  Google Scholar 

  3. Hu Y, Chen Z, Huang L, Xi Y, Li B, Wang H. A translational study on looming-evoked defensive response and the underlying subcortical pathway in autism. Sci Rep 2017, 7: 14755.

    ADS  PubMed  PubMed Central  Google Scholar 

  4. Shang C, Liu Z, Chen Z, Shi Y, Wang Q, Liu S, et al. Brain circuits. A parvalbumin-positive excitatory visual pathway to trigger fear responses in mice. Science 2015, 348: 1472–1477.

    ADS  CAS  PubMed  Google Scholar 

  5. Hong CJH, Siddiqui AM, Sabljic TF, Ball AK. Changes in parvalbumin immunoreactive retinal ganglion cells and amacrine cells after optic nerve injury. Exp Eye Res 2016, 145: 363–372.

    CAS  PubMed  Google Scholar 

  6. Sonoda T, Li JY, Hayes NW, Chan JC, Okabe Y, Belin S, et al. A noncanonical inhibitory circuit dampens behavioral sensitivity to light. Science 2020, 368: 527–531.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  7. Massey SC. Progress in Retinal Research. In: Cell types using glutamate as a neurotransmitter in the vertebrate retina. 11st ed. Elsevier Publishing, 1990: 399–425.

  8. McKee A, McHenry MJ. The strategy of predator evasion in response to a visual looming stimulus in zebrafish (Danio rerio). Integr Org Biol 2020, 2: obaa023.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Yilmaz M, Meister M. Rapid innate defensive responses of mice to looming visual stimuli. Curr Biol 2013, 23: 2011–2015.

    CAS  PubMed  Google Scholar 

  10. Cléry J, Guipponi O, Odouard S, Pinède S, Wardak C, Ben Hamed S. The prediction of impact of a looming stimulus onto the body is subserved by multisensory integration mechanisms. J Neurosci 2017, 37: 10656–10670.

    PubMed  PubMed Central  Google Scholar 

  11. Cappe C, Thut G, Romei V, Murray MM. Selective integration of auditory-visual looming cues by humans. Neuropsychologia 2009, 47: 1045–1052.

    PubMed  Google Scholar 

  12. Wang F, Li E, De L, Wu Q, Zhang Y. OFF-transient alpha RGCs mediate looming triggered innate defensive response. Curr Biol 2021, 31: 2263-2273.e3.

    CAS  PubMed  Google Scholar 

  13. McFadyen J. Investigating the subcortical route to the amygdala across species and in disordered fear responses. J Exp Neurosci 2019, 13: 1179069519846445.

    PubMed  PubMed Central  Google Scholar 

  14. Song SY, Li Y, Zhai XM, Li YH, Bao CY, Shan CJ, et al. Connection input mapping and 3D reconstruction of the brainstem and spinal cord projections to the CSF-contacting nucleus. Front Neural Circuits 2020, 14: 11.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Tsai NY, Wang F, Toma K, Yin C, Takatoh J, Pai EL, et al. Trans-Seq maps a selective mammalian retinotectal synapse instructed by Nephronectin. Nat Neurosci 2022, 25: 659–674.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Huang L, Yuan T, Tan M, Xi Y, Hu Y, Tao Q, et al. A retinoraphe projection regulates serotonergic activity and looming-evoked defensive behaviour. Nat Commun 2017, 8: 14908.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  17. Liu AL, Liu YF, Wang G, Shao YQ, Yu CX, Yang Z, et al. The role of ipRGCs in ocular growth and myopia development. Sci Adv 2022, 8: eabm027.

    Google Scholar 

  18. Sabatini PV, Wang J, Rupp AC, Affinati AH, Flak JN, Li C, et al. tTARGIT AAVs mediate the sensitive and flexible manipulation of intersectional neuronal populations in mice. Elife 2021, 10: e66835.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Lin R, Liang J, Wang R, Yan T, Zhou Y, Liu Y, et al. The raphe dopamine system controls the expression of incentive memory. Neuron 2020, 106(498–514): e498.

    Google Scholar 

  20. Wu M, Deng Q, Lei X, Du Y, Shen Y. Elavl2 regulates retinal function via modulating the differentiation of amacrine cells subtype. Invest Ophthalmol Vis Sci 2021, 62: 1.

    PubMed  PubMed Central  Google Scholar 

  21. Becht E, McInnes L, Healy J, Dutertre CA, Kwok IWH, Ng LG, et al. Dimensionality reduction for visualizing single-cell data using UMAP. Nat Biotechnol 2018, https://doi.org/10.1038/nbt.4314.

    Article  PubMed  Google Scholar 

  22. Chen F, Duan X, Yu Y, Yang S, Chen Y, Gee CE, et al. Visual function restoration with a highly sensitive and fast Channelrhodopsin in blind mice. Signal Transduct Target Ther 2022, 7: 104.

    PubMed  PubMed Central  Google Scholar 

  23. Shi C, Yuan X, Chang K, Cho KS, Xie XS, Chen DF, et al. Optimization of optomotor response-based visual function assessment in mice. Sci Rep 2018, 8: 9708.

    ADS  PubMed  PubMed Central  Google Scholar 

  24. Lee ES, Kim TJ, Jeon CJ. Identification of parvalbumin-containing retinal ganglion cells in rabbit. Exp Eye Res 2013, 110: 113–124.

    CAS  PubMed  Google Scholar 

  25. Yi CW, Yu SH, Lee ES, Lee JG, Jeon CJ. Types of parvalbumin-containing retinotectal ganglion cells in mouse. Acta Histochem Cytochem 2012, 45: 201–210.

    PubMed  PubMed Central  Google Scholar 

  26. Nadal-Nicolás FM, Jiménez-López M, Sobrado-Calvo P, Nieto-López L, Cánovas-Martínez I, Salinas-Navarro M, et al. Brn3a as a marker of retinal ganglion cells: Qualitative and quantitative time course studies in naive and optic nerve-injured retinas. Invest Ophthalmol Vis Sci 2009, 50: 3860–3868.

    PubMed  Google Scholar 

  27. Covington BP, Al Khalili Y. Neuroanatomy, Nucleus Lateral Geniculate. 2th ed. StatPearls Publishing, 2022:1–2.

  28. Liu X, Huang H, Snutch TP, Cao P, Wang L, Wang F. The superior colliculus: Cell types, connectivity, and behavior. Neurosci Bull 2022, 38: 1519–1540.

    PubMed  PubMed Central  Google Scholar 

  29. Saleeba C, Dempsey B, Le S, Goodchild A, McMullan S. A student’s guide to neural circuit tracing. Front Neurosci 2019, 13: 897.

    PubMed  PubMed Central  Google Scholar 

  30. Rutkowski AJ, Erhard F, L’Hernault A, Bonfert T, Schilhabel M, Crump C, et al. Widespread disruption of host transcription termination in HSV-1 infection. Nat Commun 2015, 6: 7126.

    ADS  PubMed  Google Scholar 

  31. Shang C, Chen Z, Liu A, Li Y, Zhang J, Qu B, et al. Divergent midbrain circuits orchestrate escape and freezing responses to looming stimuli in mice. Nat Commun 2018, 9: 1232.

    ADS  PubMed  PubMed Central  Google Scholar 

  32. Guo H, Yuan XS, Zhou JC, Chen H, Li SQ, Qu WM, et al. Whole-brain monosynaptic inputs to hypoglossal motor neurons in mice. Neurosci Bull 2020, 36: 585–597.

    PubMed  PubMed Central  Google Scholar 

  33. Huang Y, Li L, Dong K, Tang H, Yang Q, Jia X, et al. Topological shape changes weaken the innate defensive response to visual threat in mice. Neurosci Bull 2020, 36: 427–431.

    PubMed  Google Scholar 

  34. Smith KS, Bucci DJ, Luikart BW, Mahler SV. DREADDS: Use and application in behavioral neuroscience. Behav Neurosci 2016, 130: 137–155.

    PubMed  PubMed Central  Google Scholar 

  35. Jendryka M, Palchaudhuri M, Ursu D, van der Veen B, Liss B, Kätzel D, et al. Pharmacokinetic and pharmacodynamic actions of clozapine-N-oxide, clozapine, and compound 21 in DREADD-based chemogenetics in mice. Sci Rep 2019, 9: 4522.

    ADS  PubMed  PubMed Central  Google Scholar 

  36. Farrow K, Teixeira M, Szikra T, Viney TJ, Balint K, Yonehara K, et al. Ambient illumination toggles a neuronal circuit switch in the retina and visual perception at cone threshold. Neuron 2013, 78: 325–338.

    CAS  PubMed  Google Scholar 

  37. Kay JN, De la Huerta I, Kim IJ, Zhang Y, Yamagata M, Chu MW, et al. Retinal ganglion cells with distinct directional preferences differ in molecular identity, structure, and central projections. J Neurosci 2011, 31: 7753–7762.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K, Goldman M, et al. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 2015, 161: 1202–1214.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Gautam P, Hamashima K, Chen Y, Zeng Y, Makovoz B, Parikh BH, et al. Multi-species single-cell transcriptomic analysis of ocular compartment regulons. Nat Commun 2021, 12: 5675.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  40. Yan W, Laboulaye MA, Tran NM, Whitney IE, Benhar I, Sanes JR. Mouse retinal cell atlas: Molecular identification of over sixty amacrine cell types. J Neurosci 2020, 40: 5177–5195.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Schweizer N, Viereckel T, Smith-Anttila CJ, Nordenankar K, Arvidsson E, Mahmoudi S, et al. Reduced Vglut2/Slc17a6 gene expression levels throughout the mouse subthalamic nucleus cause cell loss and structural disorganization followed by increased motor activity and decreased sugar consumption. eNeuro 2016, 3: ENEURO.0264–ENEURO.0216.2016.

  42. Saunders A, Granger AJ, Sabatini BL. Corelease of acetylcholine and GABA from cholinergic forebrain neurons. Elife 2015, 4: e06412.

    PubMed  PubMed Central  Google Scholar 

  43. Choi J, Li J, Ferdous S, Liang Q, Moffitt J, Chen R. Spatial organization of the mouse retina at single cell resolution. 2022, bioRxiv 518972. doi:https://doi.org/10.1101/518972.

  44. Tan H, Li X, Huang K, Luo M, Wang L. Morphological and distributional properties of SMI-32 immunoreactive ganglion cells in the rat retina. J Comp Neurol 2022, 530: 1276–1287.

    CAS  PubMed  Google Scholar 

  45. Lee KH, Tran A, Turan Z, Meister M. The sifting of visual information in the superior colliculus. Elife 2020, 9: e50678.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Silverstein DN, Ingvar M. A multi-pathway hypothesis for human visual fear signaling. Front Syst Neurosci 2015, 9: 101.

    PubMed  PubMed Central  Google Scholar 

  47. Pessoa L, Adolphs R. Emotion processing and the amygdala: From a ‘low road’ to ‘many roads’ of evaluating biological significance. Nat Rev Neurosci 2010, 11: 773–783.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Morris JS, Ohman A, Dolan RJ. A subcortical pathway to the right amygdala mediating unseen fear. Proc Natl Acad Sci U S A 1999, 96: 1680–1685.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  49. Klump KE, Zhang AJ, Wu SM, Marshak DW. Parvalbumin-immunoreactive amacrine cells of macaque retina. Vis Neurosci 2009, 26: 287–296.

    PubMed  PubMed Central  Google Scholar 

  50. Kim T, Shen N, Hsiang JC, Johnson KP, Kerschensteiner D. Dendritic and parallel processing of visual threats in the retina control defensive responses. Sci Adv 2020, 6: eabc9920.

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  51. Weng S, Sun W, He S. Identification of ON-OFF direction-selective ganglion cells in the mouse retina. J Physiol 2005, 562: 915–923.

    CAS  PubMed  Google Scholar 

  52. Wu Q, Zhang Y. Neural circuit mechanisms involved in animals’ detection of and response to visual threats. Neurosci Bull 2023, https://doi.org/10.1007/s12264-023-01021-0.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Reinhard K, Li C, Do Q, Burke EG, Heynderickx S, Farrow K. A projection specific logic to sampling visual inputs in mouse superior colliculus. Elife 2019, 8: e50697.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Münch TA, da Silveira RA, Siegert S, Viney TJ, Awatramani GB, Roska B. Approach sensitivity in the retina processed by a multifunctional neural circuit. Nat Neurosci 2009, 12: 1308–1316.

    PubMed  Google Scholar 

  55. Kim T, Soto F, Kerschensteiner D. An excitatory amacrine cell detects object motion and provides feature-selective input to ganglion cells in the mouse retina. Elife 2015, 4: e08025.

    PubMed  PubMed Central  Google Scholar 

  56. Kim T, Kerschensteiner D. Inhibitory control of feature selectivity in an object motion sensitive circuit of the retina. Cell Rep 2017, 19: 1343–1350.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Kim IJ, Zhang Y, Meister M, Sanes JR. Laminar restriction of retinal ganglion cell dendrites and axons: Subtype-specific developmental patterns revealed with transgenic markers. J Neurosci 2010, 30: 1452–1462.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Luo X, Cai D, Shen K, Deng Q, Lei X, Jin S, et al. Superior colliculus-projecting GABAergic retinal ganglion cells mediate looming-evoked flight response. 2020, bioRxiv 090167. https://doi.org/10.1101/090167.

  59. Wei P, Liu N, Zhang Z, Liu X, Tang Y, He X, et al. Processing of visually evoked innate fear by a non-canonical thalamic pathway. Nat Commun 2015, 6: 6756.

    ADS  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the National Key R&D Program of China (2017YFE0103400) and the National Nature Science Foundation of China (81470628).

Author information

Author notes

  1. Man Yuan and Sen Jin contributed equally to this work.

Authors and Affiliations

  1. Eye Center, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, 430060, China

    Man Yuan, Gao Tan, Yizong Liu & Yin Shen

  2. The Brain Cognition and Brain Disease Institute, Shenzhen Key Laboratory of Viral Vectors for Biomedicine, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, National Medical Products Administration Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen Key Laboratory of Quality Control Technology for Virus-Based Therapeutics, Guangdong Provincial Medical Products Administration, Shenzhen, 518055, China

    Sen Jin & Huadong Wang

  3. Jan and Dan Duncan Neurological Research Institute, Baylor College of Medicine, Houston, 77030, USA

    Siyuan Song

  4. State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Innovation Academy for Precision Measurement Science and Technology, CAS, Wuhan, 430071, China

    Sen Jin & Huadong Wang

  5. Frontier Science Center of Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, 430071, China

    Yin Shen

Authors
  1. Man Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sen Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gao Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Siyuan Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yizong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Huadong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yin Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yin Shen.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 4440 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yuan, M., Jin, S., Tan, G. et al. A Non-canonical Excitatory PV RGC–PV SC Visual Pathway for Mediating the Looming-evoked Innate Defensive Response. Neurosci. Bull. 40, 310–324 (2024). https://doi.org/10.1007/s12264-023-01076-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12264-023-01076-z

Keywords

Search

Navigation