Biology subjects

von Faber-Castell, A.

Publications and source records attributed to von Faber-Castell, A..

4 recordsLinked to original sources

bioRxiv2026

Opportunistic neuronal fuelling

Neurons can utilize either glucose or lactate, yet fuel selection during periods of activity remains unresolved. By combining optical monitoring of cytosolic pyruvate and NADH with mathematical modelling, we systematically evaluated mitochondrial fuelling in cultured neurons and acute brain slices. Under substrate concentrations typical of resting brain tissue, neurons rely almost exclusively on glucose, with a minor contribution from pyruvate. However, when extracellular lactate rises to levels mimicking tissue activity, glycolysis is inhibited and lactate becomes a major substrate, irrespective of ongoing neuronal activity. Ultimately, neuronal fuel selection is dictated not by internal energy demand, but by extracellular lactate availability, which fluctuates with local glial metabolism and systemic states such as exercise. These findings redefine our understanding of short-term metabolic flexibility in the brain and underscore the significant yet understudied role of extracellular pyruvate.

physiology↗

bioRxiv2026

Developmental Trajectory of Synaptic Remodeling in the Mouse Prefrontal Cortex

The prefrontal cortex (PFC) is a heteromodal association area critical for higher-order cognitive functions. Its protracted maturation extends through adolescence into early adulthood, a period characterized by extensive remodeling of neuronal networks and synaptic architecture. This heightened plasticity supports the refinement of prefrontal circuits necessary to meet the evolving cognitive and behavioral demands of this developmental transition. However, the extended maturation window also increases vulnerability to environmental perturbations, which can lead to lasting synaptic and cognitive impairments. Despite widespread use of developmental disruption models during adolescence, a systematic characterization of synaptic dynamics during normal PFC maturation is lacking. Here, we combined longitudinal in vivo two-photon imaging of dendritic spines with cross-sectional quantification of excitatory and inhibitory synapses, and microglia-mediated synaptic engulfment, in mice from juvenile to adult stages. This integrated approach provides a comprehensive reference atlas of normal prefrontal synaptic maturation, offering a framework for interpreting alterations to synapses in models of developmental disturbance.

neuroscience↗

bioRxiv2024

A low-cost FPGA-based approach for pile-up corrected high-speed in vivo FLIM imaging

Intensity-based two-photon microscopy (2PM) is a cornerstone of biomedical research but lacks the ability to measure concentrations, a pivotal task for longitudinal studies and quantitative comparisons. Fluorescence Lifetime Imaging (FLIM) based on Time-Correlated Single Photon Counting (TCSPC) can overcome those limits but suffers from "pile-up" distortions at high photon count rates, severely limiting acquisition speed. We introduce the "laser period blind time" (LPBT) method to correct pile-up distortions in photon counting electronics, enabling reliable low-cost TCSPC-FLIM at high count rates. The correction was implemented on low-cost hardware based on a field programable gate array (FPGA) and validated using a combination of in silico simulations and in vitro, ex vivo and in vivo measurements. The LBPT approach achieves <3% error in lifetime measurements at count rates more than ten times higher than traditional limits, allowing robust FLIM imaging of sub-second metabolite dynamics with subcellular resolution. Our work enables high-precision, cost-effective FLIM imaging at rates comparable to commercial systems and at a fraction of the cost, facilitating the adoption of FLIM across all areas of research needing affordable, quantitative live imaging solutions.

neuroscience↗

bioRxiv2024

Lactate-carried Mitochondrial Energy Overflow

We addressed the question of mitochondrial lactate metabolism using genetically-encoded sensors. The organelle was found to contain a dynamic lactate pool that leads to dose- and time-dependent protein lactylation. In neurons, mitochondrial lactate reported blood lactate levels with high fidelity. The exchange of lactate across the inner mitochondrial membrane was found to be mediated by a high affinity H+-coupled transport system involving the mitochondrial pyruvate carrier MPC. Assessment of electron transport chain activity and determination of lactate flux showed that mitochondria are tonic lactate producers, a phenomenon driven by energization and stimulated by hypoxia. We conclude that an overflow mechanism caps the redox level of mitochondria, while saving energy in the form of lactate. One Sentence SummaryMitochondrial lactate production

biochemistry↗