Biology subjects

Dunn, F. A.

Publications and source records attributed to Dunn, F. A..

4 recordsLinked to original sources

bioRxiv2026

Protein tyrosine phosphatase receptor type kappa (PTPRκ) regulates Superior ON-Direction Selective Ganglion Cell development, facilitating image stabilization

In vertebrates, gaze stabilization during global visual motion requires ON direction-selective ganglion cells (oDSGCs) in the Accessory Optic System (AOS) to drive the optokinetic reflex (OKR). Three types of oDSGCs form independent mosaics; however, the mechanisms that specify and maintain their numbers to create these mosaics during development remain unknown. Here, we identify protein tyrosine phosphatase receptor type kappa (Ptprk) as a key regulator of Superior oDSGC density, the subtype tuned to upward motion. High-depth single-cell RNA sequencing (scRNAseq) reveals that Ptprk is selectively enriched in Superior oDSGCs compared to Inferior oDSGCs, which detect downward motion. Genetic deletion of Ptprk selectively halves the number of Superior oDSGCs while preserving the number of Inferior oDSGCs. Anatomically, Superior oDSGCs in Ptprk mutants exhibit compensatory neurite remodeling to preserve mosaics. Physiologically, oDSGCs have broader tuning curves, and a subset of Superior oDSGCS have aberrant preferred directions in Ptprk mutants. Postsynaptically, loss of Ptprk reduces oDSGC connectivity to central targets. Behaviorally, the OKR responses to upward motion are attenuated in both global and pan-retinal Ptprk mutants, confirming a retinal role for Ptprk in upward image stabilization. Together, these findings demonstrate that the density of a retinal ganglion cell type is under molecular control, and that reducing density drives neurite remodeling, alters circuit computation, and ultimately impairs visually-guided behavior.

neuroscience↗

bioRxiv2025

Partial Input Loss Differentially Modifies Neural Pathways

Following input loss from degeneration, injury, and/or aging, downstream circuits undergo modifications that can impact neural computations. How neural computations across different pathways are affected by common input loss remain understudied. To leverage known cell types, well-defined circuitry, and molecular tools, we use the mouse retina to show how multiple pathways adjust their functional properties differently to common input loss and further locate these changes within each pathway. Specifically, we asked if two OFF ganglion cell types, alpha OFF-sustained (AOFF-S) and OFF-transient (AOFF-T) cells, and their respective dominant presynaptic partners, type 2 and type 3a cone bipolar cells, respond differentially to partial cone loss. We find that AOFF-T ganglion cells exhibit more circuit changes than AOFF-S ganglion cells, resulting in altered spatiotemporal tuning following partial cone loss. We show that the underlying mechanisms include changes in glutamatergic, GABAergic, and glycinergic circuits in the pathway of AOFF-T ganglion cells. In response to common input loss, our study finds different locations of circuit modifications across OFF pathways. These findings provide insight into how sensory pathways can compensate differentially to common input loss.

neuroscience↗

bioRxiv2024

Tau P301S Transgenic Mice Develop Gait and Eye Movement Impairments That Mimic Progressive Supranuclear Palsy

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder with an estimated prevalence of 5-7 people in 100,000. Clinically characterized by impairments in gait, balance, and eye movements, as well as aggregated Tau pathology, PSP leads to death in approximately 5-8 years. No disease-modifying treatments are currently available. The contribution of Tau pathology to the symptoms of patients with PSP is poorly understood, in part due to lack of a rodent model that recapitulates characteristic aspects of PSP. Here, we assessed the hTau.P301S mouse for key clinical features of PSP, finding progressive impairments in balance and gait coordination. Additionally, we found impairments in fast vertical eye movements, one of the most distinctive features of PSP. Across animals, we found that Tau pathology in motor control regions correlated with motor deficits. These findings highlight the utility of the hP301S mouse in modeling key aspects of PSP.

neuroscience↗

bioRxiv2022

Asymmetric retinal direction tuning predicts optokinetic eye movements across stimulus conditions

Across species, the optokinetic reflex (OKR) stabilizes vision during self-motion. OKR occurs when ON direction-selective retinal ganglion cells (oDSGCs) detect slow, global image motion on the retina. How oDSGC activity is integrated centrally to generate behavior remains unknown. Here, we discover mechanisms that contribute to motion encoding in vertically-tuned oDSGCs, and leverage these findings to empirically define signal transformation between retinal output and vertical OKR behavior. We demonstrate that motion encoding in vertically-tuned oDSGCs is contrast-sensitive and asymmetric for oDSGC types that prefer opposite directions. These phenomena arise from the interplay between spike threshold nonlinearities and differences in synaptic input weights, including shifts in the balance of excitation and inhibition. In behaving mice, these neurophysiological observations, along with a central subtraction of oDSGC outputs, accurately predict the trajectories of vertical OKR across stimulus conditions. Thus, asymmetric tuning across competing sensory channels can critically shape behavior.

neuroscience↗