Summary: New research reveals that the loss of a single ion channel, TRPM1, is enough to produce persistent rhythmic oscillations in the retina, a feature observed in both congenital stationary night blindness and retinitis pigmentosa. By comparing Trpm1 and mGluR6 knockout mice, researchers identified a disrupted circuit between rod bipolar cells and AII amacrine cells that produces anti-phase oscillations interfering with visual signaling.
Structural remodeling and hyperpolarized bipolar cells further destabilize retinal networks, generating spontaneous noise that distorts perception. These findings underscore the need for vision restoration therapies to address both photoreceptor loss and oscillatory neural activity to achieve clear, stable vision.
Key Facts
- TRPM1 Loss Drives Oscillations: Eliminating the TRPM1 ion channel disrupts ON-bipolar signaling and produces pathological retinal oscillations.
- Circuit Instability Identified: Weak rod bipolar–AII amacrine cell coupling and anti-phase signaling generate the rhythmic neural noise.
- Therapeutic Implication: Restoring vision will require stabilizing these oscillations to prevent distorted or hallucinatory perception.
Source: Ritsumeikan University
Rhythmic electrical activity in the retina (known as pathological oscillations) has been observed in several eye diseases, including congenital stationary night blindness (CSNB) and retinitis pigmentosa (RP).
These oscillations interfere with the normal transmission of visual information to the brain, often causing degraded or distorted perception.
Although scientists have long known that such oscillations occur in retinal ganglion cells (RGCs), the neurons responsible for sending visual signals to the brain, the cellular mechanism that drives this rhythmic activity has remained elusive.
In a recent study published online in The Journal of General Physiology on October 16, 2025, led by Mr. Sho Horie, a PhD candidate, from the Graduate School of Pharmacy, Ritsumeikan University, Japan, along with Professor Katsunori Kitano, Professor Masao Tachibana, and Professor Chieko Koike, from Center for Systems Vision Science, Ritsumeikan University, revealed that the loss of a single ion channel—TRPM1—sets off a cascade of changes that lead to persistent oscillations in the retina.
Their findings not only illuminate the cellular basis of CSNB but also identify a common mechanism underlying retinal degenerative conditions, such as RP.
TRPM1, a visual signal transduction channel found in retinal ON bipolar cells, is regulated by the metabotropic glutamate receptor, mGluR6. The genes associated with these channels (Trpm1 and mGluR6) are known to cause CSNB when mutated, yet they produce subtly different effects on retinal circuitry.
“Most of the phenotypes of the respective gene knockout mice are coincidental, but only the Trpm1 knockout (KO) mouse retina has spontaneous oscillation. Hence, we tried to figure out the difference between Trpm1 and mGluR6 KO mice,” explains Mr. Horie.
Using whole-cell clamp recordings and computational modeling, the team examined how TRPM1 loss alters retinal signaling. They found that in Trpm1 KO mice, inhibitory and excitatory inputs to RGCs oscillate in opposite phases, creating anti-phase rhythmic activity between OFF and ON pathways.
Blocking specific synaptic and gap junction pathways silenced these oscillations, pinpointing the source to a disrupted circuit involving rod bipolar cells (RBCs) and AII amacrine cells (ACs).
The researchers also observed physical remodeling of the retina: the axon terminals of RBCs in Trpm1 KO mice were smaller and mispositioned, similar to changes seen in retinal degeneration (rd1) mice, a model for the degenerative disease, RP. These structural abnormalities correlated with a hyperpolarized resting potential in RBCs, weakening their communication with ACs.
“Under certain pathological conditions, RGCs can display spontaneous oscillatory activity,” notes Prof. Koike. “This ‘noise’ disrupts visual information processing and can cause hallucinations. Our study reveals why such oscillations occur in Trpm1 KO mice and suggests that the same mechanism drives them in degenerative diseases like RP.”
The researchers were able to replicate the oscillatory firing patterns seen experimentally by incorporating these structural and electrical changes into a computational model. The model confirmed that reduced synaptic strength between RBCs and ACs, combined with hyperpolarization of ON bipolar cells, is sufficient to trigger pathological rhythmic firing.
Prof. Kitano adds, “Our simulations show that even small reductions in bipolar cell output can destabilize retinal circuits, leading to oscillations that mask real visual signals.”
The study provides critical insight into how disruptions in TRPM1-dependent signaling can lead to neural noise across different retinal pathologies. Importantly, it suggests that therapies restoring vision (such as regenerative medicine or optogenetic treatment) should also address these oscillations to ensure patients regain clear vision, not distorted or hallucinatory perception.
The team hopes their findings will pave the way for new therapeutic approaches to stabilize retinal activity and improve outcomes in vision restoration treatments.
Funding information
This work was supported by the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (Grants Nos. 24H00747, 22KK0137, 19H01140, and 24390019), Takeda Science Foundation, the Kobayashi Foundation, JST PRESTO, and R-GIRO.
Key Questions Answered:
A: Loss of the TRPM1 ion channel disrupts ON-bipolar cell signaling, triggering circuit changes that generate persistent oscillations.
A: It weakens rod bipolar cell–AII amacrine cell communication and creates anti-phase oscillations across ON and OFF pathways.
A: Retinal oscillations act as neural noise that can distort or mask visual signals, meaning future therapies must also stabilize circuit activity.
Editorial Notes
- This article was written by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this genetics and visual neuroscience research news
Author: Yuhki Nakajima
Source: Ritsumeikan University
Contact: Yuhki Nakajima – Ritsumeikan University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“A mechanism for pathological oscillations in mouse retinal ganglion cells in a model of night blindness” by Sho Horie et al. Journal of General Physiology
Abstract
A mechanism for pathological oscillations in mouse retinal ganglion cells in a model of night blindness
TRPM1 channels, regulated by mGluR6 at the dendrites of retinal ON bipolar cells (BCs), play a crucial role in visual signal transduction. Both Trpm1 knockout (KO) and mGluR6 KO mice are models of congenital stationary night blindness with grossly normal morphology.
However, robust pathological spontaneous oscillations in retinal ganglion cells (RGCs) have been observed in Trpm1 KO retinas but not in mGluR6 KO retinas.
We investigated the mechanism underlying these oscillations in the Trpm1 KO retina using whole-cell clamp techniques.
We found that inhibitory and excitatory synaptic inputs produced anti-phase oscillations in OFF and ON RGCs, respectively, and that oscillations could be suppressed by blockers targeting the AII amacrine cell (AC) pathway.
The rd1 retina, a model for retinitis pigmentosa with severe photoreceptor degeneration, displays similar oscillations to the Trpm1 KO retina. Morphological and immunohistochemical analyses revealed similar alterations in the Trpm1 KO and rd1 retinas when compared to the mGluR6 KO and wild-type retinas: namely, rod BCs (RBCs) in both Trpm1 KO and rd1 retinas showed reduced dendritic TRPM1 labeling and smaller axon terminals.
Furthermore, RBCs in the Trpm1 KO retina were significantly hyperpolarized. In silico simulation of the BC-AII AC-RGC network suggests that the reduction of RBC and ON cone BC outputs to AII ACs contributes to RGC oscillations.
Our findings suggest that TRPM1 deficiency in ON BCs produces RGC oscillations in association with RBC axon remodeling and reduced ON BC outputs, and may represent a shared circuit mechanism underlying pathological oscillations across different causes of outer retinal diseases.
