Biology subjects

Calbiague Garcia, V. M.

Publications and source records attributed to Calbiague Garcia, V. M..

3 recordsLinked to original sources

bioRxiv2026

Gamma-frequency firing persistently enhances intrinsic excitability in retinal ganglion cells

Experience-dependent plasticity is usually attributed to synaptic changes, but neuronal output also depends on changes in intrinsic excitability. Whether intrinsic excitability is persistently modified at the retinal output stage is unknown. Using whole-cell recordings from retinal ganglion cells (RGCs) of juvenile rats, we found that 40-Hz firing produced sustained potentiation of intrinsic excitability in low-input-resistance A-type RGCs and rapid potentiation of intrinsic excitability in high-input-resistance B-type RGCs. In A-type bursting RGCs, long-term potentiation of intrinsic excitability (LTP-IE) required Cav1 calcium channels for its induction. LTP-IE was associated with hyperpolarization of spike threshold and reduction of spike time jitter, due to reduced Kv1 potassium-family channel function. Potentiation also increased the probability that visually-evoked synaptic events triggered action potentials. Patterned firing therefore persistently reconfigures RGC input-output transformation through the Cav1-dependent regulation of Kv1 channels, revealing intrinsic plasticity at the retinal output stage.

neuroscience↗

bioRxiv2026

Evidence for a rod-to-cone lactate shuttle in the mammalian retina

In his seminal 1920s studies, Otto Warburg found the retina to generate large amounts of lactate. However, it was unclear what retinal cells produced lactate and whether it was a metabolic waste product or used further. Here, we show that lactate produced by rod photoreceptors fuels the energy-intensive function and viability of cone photoreceptors. In an initial expression analysis, we found monocarboxylate transporter-1 (MCT1), lactate-producing lactate-dehydrogenase-A (LDHA), and pyruvate carboxykinase-1 (PCK1) localized to rod photoreceptors, while high-affinity MCT2, pyruvate-producing LDHB, and PCK2 were expressed in cones. We then exposed retina to defined media containing either glucose or lactate as caloric component, and applied specific MCT inhibitors. In glucose-containing medium, 1H-NMR metabolomics showed rod MCT1 inhibition to increase retinal lactate, suggesting rods as a major source of lactate. In lactate-only medium, functional recordings using micro-electroretinography showed decreased rod function, while cone function was maintained. In glucose-containing medium, blocking rod MCT1 abolished cone function. Long-term treatment with MCT inhibitors selectively decreased photoreceptor viability. Conversely, supplementing the defined medium with lactate preserved cone viability in the rd1 mouse model for Retinitis Pigmentosa. Together, our data suggest that lactate shuttling from rods is crucial for cone function and viability. This may explain cone degeneration seen in various retinal diseases and provides an entirely new avenue for metabolism-based treatment development. The discovery of a lactate-shuttle between two functionally similar, yet distinct types of neurons may have far-reaching implications for our understanding of the central nervous system in general.

neuroscience↗

bioRxiv2022

Imaging of lactate metabolism in retinal Müller cells with a FRET nanosensor

Muller cells, the glial cells of the retina, provide metabolic support for photoreceptors and inner retinal neurons, and have been proposed as source of the significant lactate production of this tissue. To better understand the role of lactate in retinal metabolism, we expressed a lactate and a glucose nanosensor in organotypic mouse retinal explants cultured for 14 days, and used FRET imaging in acute vibratome sections of the explants to study metabolite flux in real time. Pharmacological manipulation with specific monocarboxylate transporter (MCT) inhibitors and immunohistochemistry revealed the functional expression of MCT2 and MCT4 in Muller cells. The introduction of nanosensors to measure key metabolites at the cellular level may contribute to a better understanding of heretofore poorly understood issues in retinal metabolism.

cell biology↗