Unveiling Glial Heterogeneity in the Inner Retina: Non-Visual Photic Spectrum Responses and Calcium Dynamics in Müller Glial Cells vs. Neurons
- 1CIQUIBIC-CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina
- 2Departamento de Química Biológica “Ranwel Caputto”, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba 5000, Argentina
Abstract
Traditional calcium (Ca2+) imaging analysis often overlooks the non-stationary temporal complexity inherent in retinal circuits, reducing dynamic signaling traces to static summary descriptors. To resolve these dynamic signatures, we implemented a reproducible analytical framework combining Continuous Wavelet Transform (CWT) time-frequency decomposition with Sinc baseline filtering and Ward’s agglomerative hierarchical clustering, applied directly to standardized high-dimensional feature spaces, reserving Uniform Manifold Approximation and Projection (UMAP) strictly for low-dimensional visualization. This pipeline was deployed across three independent experimental models under blue light stimulation: mixed primary embryonic chicken retinal neurons, primary chicken Müller glial cells (MGCs), and the human MIO-M1 Müller cell line. Functional clustering resolved retinal neurons into three distinct kinetic subpopulations (k = 3), characterized by a kinetically stable core maintaining mid-frequency oscillations (Cluster 0), a cohort undergoing sharp post-stimulus period contraction with late amplitude surges (Cluster 1), and a low-frequency cohort with persistent period elongation (Cluster 2). Chicken MGCs partitioned into two operational clusters (k = 2), contrasting a period-stable, amplitude-decaying subpopulation (Cluster 0) with a dynamic subpopulation exhibiting light-evoked kinetic acceleration (Cluster 1). Similarly, human MIO-M1 glia separated into two major kinetic clusters (k = 2), distinguishing a low-amplitude, longer-period cohort from a high-amplitude, sustained subpopulation operating within an 8–80 s dynamic period band. Restricting phase-coupling and circular statistical analyses strictly to simultaneous Field-of-View (FOV) recordings revealed distinct stimulus-entrained network behaviors: primary avian MGCs maintain a decentralized, weakly coupled regime (“mosaic of autonomy”) that processes light across independent temporal windows, whereas human MIO-M1 glia and embryonic neuronal assemblies exhibit significant stimulus-evoked phase realignment and relative response latency sequencing. These findings demonstrate that inner retinal functional identity is fundamentally rhythmic and cluster-dependent, establishing a quantitative benchmark for decoding multi-scale Ca2+ signaling in healthy retinal preparations.
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BibTeX
@article{rios2026unveiling,
title = {{Unveiling Glial Heterogeneity in the Inner Retina: Non-Visual Photic Spectrum Responses and Calcium Dynamics in Müller Glial Cells vs. Neurons}},
author = {Maximiliano N. Rios and Natalia A. Marchese and Mario E. Guido},
journal = {International journal of molecular sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198879},
url = {https://europepmc.org/article/PMC/PMC13665424},
note = {CC BY},
}
RIS
TY - JOUR
TI - Unveiling Glial Heterogeneity in the Inner Retina: Non-Visual Photic Spectrum Responses and Calcium Dynamics in Müller Glial Cells vs. Neurons
AU - Maximiliano N. Rios
AU - Natalia A. Marchese
AU - Mario E. Guido
PY - 2026
DA - 2026/10/01
JO - International journal of molecular sciences
DO - 10.3390/ijms27198879
UR - https://europepmc.org/article/PMC/PMC13665424
AB - Traditional calcium (Ca2+) imaging analysis often overlooks the non-stationary temporal complexity inherent in retinal circuits, reducing dynamic signaling traces to static summary descriptors. To resolve these dynamic signatures, we implemented a reproducible analytical framework combining Continuous Wavelet Transform (CWT) time-frequency decomposition with Sinc baseline filtering and Ward’s agglomerative hierarchical clustering, applied directly to standardized high-dimensional feature spaces, reserving Uniform Manifold Approximation and Projection (UMAP) strictly for low-dimensional visualization. This pipeline was deployed across three independent experimental models under blue light stimulation: mixed primary embryonic chicken retinal neurons, primary chicken Müller glial cells (MGCs), and the human MIO-M1 Müller cell line. Functional clustering resolved retinal neurons into three distinct kinetic subpopulations (k = 3), characterized by a kinetically stable core maintaining mid-frequency oscillations (Cluster 0), a cohort undergoing sharp post-stimulus period contraction with late amplitude surges (Cluster 1), and a low-frequency cohort with persistent period elongation (Cluster 2). Chicken MGCs partitioned into two operational clusters (k = 2), contrasting a period-stable, amplitude-decaying subpopulation (Cluster 0) with a dynamic subpopulation exhibiting light-evoked kinetic acceleration (Cluster 1). Similarly, human MIO-M1 glia separated into two major kinetic clusters (k = 2), distinguishing a low-amplitude, longer-period cohort from a high-amplitude, sustained subpopulation operating within an 8–80 s dynamic period band. Restricting phase-coupling and circular statistical analyses strictly to simultaneous Field-of-View (FOV) recordings revealed distinct stimulus-entrained network behaviors: primary avian MGCs maintain a decentralized, weakly coupled regime (“mosaic of autonomy”) that processes light across independent temporal windows, whereas human MIO-M1 glia and embryonic neuronal assemblies exhibit significant stimulus-evoked phase realignment and relative response latency sequencing. These findings demonstrate that inner retinal functional identity is fundamentally rhythmic and cluster-dependent, establishing a quantitative benchmark for decoding multi-scale Ca2+ signaling in healthy retinal preparations.
SN - 1422-0067
ER -