Biology subjects

Garcia del Molino, L. C.

Publications and source records attributed to Garcia del Molino, L. C..

2 recordsLinked to original sources

bioRxiv2018

Inorganic polyphosphate (polyP) is required for sustained free mitochondrial calcium elevation, following stimulated calcium uptake.

Mitochondrial free calcium is critically linked to the regulation of bioenergetics and cellular signaling. Free calcium concentrations within the organelle are regulated by two processes: flux across the mitochondrial inner membranes and buffering by phosphate. The key role of phosphate in the buffering of free calcium in mitochondria is well-established. Specifically, during stimulated calcium uptake, calcium is partially buffered by orthophosphate, allowing for elevated calcium concentrations, while preventing calcium toxicity. However, this buffering system is expected to lead to the irreversible formation of insoluble precipitates, which are not observed in living cells, under physiological conditions. Here, we demonstrate that the regulation of free mitochondrial calcium requires the presence of free inorganic polyphosphate (polyP) within the organelle. Specifically, we found that the overexpression of a mitochondrial-targeted enzyme hydrolyzing polyP, leads to the loss of the cellular ability to maintain elevated calcium concentrations within the organelle, following stimulated cytoplasmic signal. We hypothesize that the presence of polyP prevents the formation of calcium-phosphate insoluble clusters, allowing for the maintenance of elevated free calcium levels, during stimulated calcium uptake.

molecular biology↗

bioRxiv2017

Response Reversal During Top-Down Modulation In Cortical Circuits With Multiple Interneuron Types

Pyramidal cells and interneurons expressing parvalbumin, somatostatin, or vasoactive intestinal peptide show cell type-specific connectivity patterns leading to a canonical microcircuit across cortex. Dissecting the dynamics of this microcircuit is essential to our understanding of the mammalian cortex. However, experiments recording from this circuit often report counterintuitive and seemingly contradictory findings. For example, the response of a V1 neural population to top-down behavioral modulation can reverse from positive to negative when the bottom-up thalamic input changes. We developed a theoretical framework to explain such response reversal, and we showed how this complex dynamics can emerge in circuits that possess two key features: the presence of multiple interneuron populations and a non-linear dependence between the input and output of the populations. Furthermore, we built a cortical circuit model and the comparison of our simulations with real data shows that our model reproduces the complex dynamics observed experimentally in mouse V1. Our explicit calculations allowed us to pinpoint the connections critical to response reversal, and to predict the existence of more types of complex dynamics that could be experimentally tested and the conditions to observe them.

neuroscience↗