Postsynaptic neuronal activity promotes regeneration of retinal axons

Supraja G Varadarajan; Fei Wang; Onkar S Dhande; Phung Le; Xin Duan; Andrew D Huberman

doi:10.1016/j.celrep.2023.112476

Postsynaptic neuronal activity promotes regeneration of retinal axons

Cell Rep. 2023 May 30;42(5):112476. doi: 10.1016/j.celrep.2023.112476. Epub 2023 May 3.

Authors

Supraja G Varadarajan¹, Fei Wang², Onkar S Dhande³, Phung Le³, Xin Duan⁴, Andrew D Huberman⁵

Affiliations

¹ Department of Neurobiology, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: suprajav@stanford.edu.
² Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA.
³ Department of Neurobiology, Stanford University School of Medicine, Stanford, CA, USA.
⁴ Department of Ophthalmology, University of California, San Francisco, San Francisco, CA, USA; Department of Physiology, University of California, San Francisco, San Francisco, CA, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA, USA.
⁵ Department of Neurobiology, Stanford University School of Medicine, Stanford, CA, USA; Department of Ophthalmology, Stanford University School of Medicine, Stanford, CA, USA; BioX, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: adh1@stanford.edu.

Abstract

The wiring of visual circuits requires that retinal neurons functionally connect to specific brain targets, a process that involves activity-dependent signaling between retinal axons and their postsynaptic targets. Vision loss in various ophthalmological and neurological diseases is caused by damage to the connections from the eye to the brain. How postsynaptic brain targets influence retinal ganglion cell (RGC) axon regeneration and functional reconnection with the brain targets remains poorly understood. Here, we established a paradigm in which the enhancement of neural activity in the distal optic pathway, where the postsynaptic visual target neurons reside, promotes RGC axon regeneration and target reinnervation and leads to the rescue of optomotor function. Furthermore, selective activation of retinorecipient neuron subsets is sufficient to promote RGC axon regeneration. Our findings reveal a key role for postsynaptic neuronal activity in the repair of neural circuits and highlight the potential to restore damaged sensory inputs via proper brain stimulation.

Keywords: CP: Neuroscience; axons; central nervous system; distal injury; neural activity; optic; postsynaptic neurons; regeneration; retinal ganglion cells; sensory systems; vision.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Axons* / metabolism
Nerve Regeneration / physiology
Retina / metabolism
Retinal Ganglion Cells / metabolism
Retinal Neurons*

Abstract

Publication types

MeSH terms

Grants and funding