Biology subjects

Garcia-Hernandez, R.

Publications and source records attributed to Garcia-Hernandez, R..

3 recordsLinked to original sources

bioRxiv2025

A sensitivity-consistency trade-off in memory formation regulated by dentate gyrus inhibition

A core computational challenge for memory systems is the need to balance two opposing demands: (1) sensitivity to subtle input differences for flexible encoding, and (2) consistency to preserve stable, interference-resistant representations. How the brain dynamically regulates this trade-off remains unclear. Here, we show that modulating parvalbumin-expressing (PV+) interneurons in the dentate gyrus regulates this balance by shifting hippocampal computation between sensitivity and consistency regimes. Combining cell-type-specific pharmacogenetics, behavioral assays, and computational modeling, we found that reducing PV+-mediated inhibition during encoding enhanced the subsequent discrimination of similar inputs but it increased vulnerability to interference. In contrast, increased inhibition stabilized memory representations at the cost of discriminability. Together, the results establish PV+ interneurons as key modulators of hippocampal memory processing, enabling the system to prioritize either flexible updating or robust retention based on inhibitory tone at the time of encoding. This sensitivity-consistency continuum may reflect a fundamental organizing principle of memory computation.

neuroscience↗

bioRxiv2020

Hippocampal dentate gyrus coordinates brain-wide communication and memory updating through an inhibitory gating

Distinct forms of memory processing are often causally identified with specific brain regions, but a key facet of memory processing includes linking separated neuronal populations. Using cell-specific manipulations of inhibitory neuronal activity, we discovered a key role of the dentate gyrus (DG) in coordinating dispersed neuronal populations during memory formation. In whole-brain fMRI and electrophysiological experiments, we found that parvalbumin (PV) interneurons in the DG control the functional coupling of the hippocampus within a wider network of neocortical and subcortical structures including the prefrontal cortex (PFC) and the nucleus accumbens (NAc). In a novel object-location task, regulation of PV interneuron activity enhanced or prevented memory encoding and, without effect upon the total number of task activated c-Fos+ cells, revealed a correlation between activated neuronal populations in the hippocampus-PFC-NAc network. These data suggest a critical regulatory role of PV interneurons in the dentate gyrus in brain-wide polysynaptic communication channels and the association of cell assemblies across multiple brain regions.

neuroscience↗

bioRxiv2020

Imaging Microglia and Astrocytes non-invasively using Diffusion MRI

Glia, and particularly microglia, are increasingly implicated in the pathophysiology of psychiatric and neurodegenerative disorders. However, to date the only methods for imaging these cells in vivo involve either invasive procedures (e.g. multi-photon imaging in rodents) or TSPO-PET radiotracers, which afford low resolution and specificity, since TSPO expresses across multiple cell types. Here, we present a non-invasive diffusion-weighted MRI method to image changes in glia morphometry in vivo. Using two rat models of neuroinflammation, with and without neurodegeneration, we demonstrate that diffusion-weighted MRI carries the fingerprint of microglia and astrocytes activation, and that specific signatures from each population can be quantified non-invasively. We demonstrate that the method can further detect glia proliferation, and provide a quantitative account of neuroinflammation regardless of the existence of a concomitant neuronal loss. We prove the translational value of the approach showing significant correlations between MRI and histological microglia markers measured across different brain regions in humans. This framework holds the potential to transform basic and clinical research by providing a tool to clarify the role of inflammation in health and disease across the lifespan.

neuroscience↗