Biology subjects

Herrera, B.

Publications and source records attributed to Herrera, B..

5 recordsLinked to original sources

bioRxiv2026

Circuit and cell-type mechanisms of the spectrolaminar motif of cortical oscillations

Oscillations are a key feature of cortical activity, coordinating spike timing across areas, layers, and cell types. Recent work suggests these rhythms follow a stereotyped organization across cortical depth, the spectrolaminar (SL) motif, with higher-frequency gamma prominent in superficial layers and lower-frequency alpha/beta in deep layers, yet the mechanisms generating it remain poorly understood. Using a bio-realistic model of mouse primary visual cortex, we reproduced the SL motif and found it preserved across diverse visual stimuli. Systematic cell-type- and layer-resolved perturbations showed that the alpha/beta component was intrinsic to every layer, whereas the 50-80 Hz gamma component was predominantly generated within layer 4 (L4) and propagated network-wide through inter-laminar connections. Pvalb interneurons were the principal regulators of gamma, Sst cells shaped low-frequency power, and Vip cells controlled oscillation magnitude. The temporal properties of L4 Pvalb-to-excitatory synapses were especially influential in generating the SL motif. These models and simulation results thus offer a plausible description of circuit mechanisms underlying cortical oscillations and the SL motif and are publicly available to facilitate further studies.

neuroscience↗

bioRxiv2023

The hepatocyte Epidermal Growth Factor Receptor (EGFR) pathway regulates the cellular interactome within the liver fibrotic niche

Background & AimsLiver fibrosis is the consequence of chronic liver injury in the presence of an inflammatory component. Although the main executors of this activation are known, the mechanisms that lead to the inflammatory process that mediates the production of profibrotic factors are not well characterized. The Epidermal Growth Factor Receptor (EGFR) signaling in hepatocytes is essential for the regenerative process of the liver; however, its potential role in regulating the fibrotic niche is not yet clear. Approach & ResultsOur group generated a mouse model that expresses an inactive truncated form of the EGFR specifically in hepatocytes ({Delta}EGFR mice). Here, we have analyzed the response of WT and {Delta}EGFR mice to chronic treatment with CCl4. Resultsindicated that the hallmarks of liver fibrosis were attenuated in CCl4-treated {Delta}EGFR mice when compared to WT mice, coinciding with a faster resolution of the fibrotic process and an ameliorated damage. The absence of EGFR activity in hepatocytes induced changes in the pattern of immune cells in the liver, with a notable change in the population of M2 macrophages, more related to fibrosis resolution, as well as an increase in the population of lymphocytes related to eradication of the damage. Transcriptomic analysis of hepatocytes and secretome studies from extracellular media in in vitro studies allowed to elucidate the specific molecular mechanisms regulated by EGFR that mediate hepatocyte production of both pro-inflammatory and pro-fibrotic mediators. ConclusionsOur results support a pro-inflammatory and pro-fibrogenic role for the hepatocyte EGFR pathway during chronic liver damage.

pathology↗

bioRxiv2023

Cortical Origin of Theta Error Signals

A multi-scale approach elucidated the origin of the error-related-negativity (ERN), with its associated theta-rhythm, and the post-error-positivity (Pe) in macaque supplementary eye field (SEF). Using biophysical modeling, synaptic inputs to layer-3 (L3) and layer-5 (L5) pyramidal cells (PCs) were optimized to account for error-related modulation and inter-spike intervals. The intrinsic dynamics of dendrites in L5 but not L3 PCs generate theta rhythmicity with random phase. Saccades synchronized the phase of this theta-rhythm, which was magnified on errors. Contributions from L5 PCs to the laminar current source density (CSD) observed in SEF were negligible. The CSD derived from L3 PCs could not explain the observed association between their error-related spiking modulation and scalp-EEG. Laminar CSD comprises multipolar components, with dipoles explaining ERN features, and quadrupoles reproducing those for Pe. The presence of monopoles indicates diffuse activation. These results provide the most advanced explanation of the cellular mechanisms generating the ERN.

neuroscience↗

bioRxiv2022

Resolving the mesoscopic missing link: Biophysical modeling of EEG from cortical columns in primates

Event-related potentials (ERP) are among the most widely measured indices for studying human cognition. While their timing and magnitude provide valuable insights, their usefulness is limited by our understanding of their neural generators at the circuit level. Inverse source localization offers insights into such generators, but their solutions are not unique. To address this problem, scientists have assumed the source space generating such signals comprises a set of discrete equivalent current dipoles, representing the activity of small cortical regions. Based on this notion, theoretical studies have employed forward modeling of scalp potentials to understand how changes in circuit-level dynamics translate into macroscopic ERPs. However, experimental validation is lacking because it requires in vivo measurements of intracranial brain sources. Laminar local field potentials (LFP) offer a mechanism for estimating intracranial current sources. Yet, a theoretical link between LFPs and intracranial brain sources is missing. Here, we present a forward modeling approach for estimating mesoscopic intracranial brain sources from LFPs and predict their contribution to macroscopic ERPs. We evaluate the accuracy of this LFP-based representation of brain sources utilizing synthetic laminar neurophysiological measurements and then demonstrate the power of the approach in vivo to clarify the source of a representative cognitive ERP component. To that end, LFP was measured across the cortical layers of visual area V4 in macaque monkeys performing an attention demanding task. We show that area V4 generates dipoles through layer-specific transsynaptic currents that biophysically recapitulate the ERP component through the detailed forward modeling. The constraints imposed on EEG production by this method also revealed an important dissociation between computational and biophysical contributors. As such, this approach represents an important bridge from the mesoscopic activity of cortical columns to the patterns of EEG we measure at the scalp. HighlightsO_LICognitive EEG production was accurately modeled from empirically measured cortical activity in awake macaques. C_LIO_LIV4 laminar activity plausibly generates the attention-related signal indexed by the EEG. C_LIO_LIModels demonstrate the importance of biophysical geometry in cognitive EEG production. C_LI

neuroscience↗

bioRxiv2020

A Minimal Biophysical Model of Neocortical Pyramidal Cells: Implications for Frontal Cortex Microcircuitry and Field Potential Generation

Ca2+ spikes initiated in the apical dendrites of layer-5 pyramidal cells (PC) underlie nonlinear dynamic changes in the gain of cellular response, which is critical for top-down cognitive control. Detailed models with several compartments and dozens of ionic channels have been proposed to account for this Ca2+ spike-dependent gain with its associated critical frequency. However, current models do not account for all known Ca2+-dependent features. Previous attempts to include more features have required increasing complexity, limiting their interpretability and utility for studying large population dynamics. We present a minimal 2-compartment biophysical model, overcoming these limitations. In our model, a basal-dendritic/somatic compartment included typical Na+ and K+ conductances, while an apical-dendritic/trunk compartment included persistent Na+, hyperpolarization-activated cation (Ih), slow inactivation K+, muscarinic K+, and Ca2+ L-type. The model replicated the Ca2+ spike morphology and its critical frequency plus three other defining features of layer-5 PC synaptic integration: linear frequency-current relationships, backpropagation-activated Ca2+ spike firing, and a shift in the critical frequency by blocking Ih. Simulating 1,000 synchronized layer-5 PCs, we reproduced the current source density patterns evoked by Ca2+-spikes both with and without Ih current. Thus, a 2-compartment model with five non-classic ionic currents in the apical-dendrites reproduces all features of these neurons. We discuss the utility of this minimal model to study the microcircuitry of agranular areas of the frontal lobe involved in cognitive control and responsible for event-related potentials such as the error-related negativity. Significance StatementA tractable model of layer-5 pyramidal cells replicates all known features crucial for distal synaptic integration in these neurons. This minimal model enables new multi-scale investigations of microcircuit functions with associated current flows measured by intracranial local field potentials. It thus establishes a foundation for the future computational evaluation of scalp electroencephalogram signatures imprinted by Ca2+ spikes in pyramidal cells, a phenomenon underlying many brain cognitive processes.

neuroscience↗