Biology subjects

Manjarrez, E.

Publications and source records attributed to Manjarrez, E..

5 recordsLinked to original sources

bioRxiv2026

The dendritic spine vicinome: characterizing its crowding in the human brain with petavoxel electron microscopy

For more than a century we have pictured the dendritic spine as the postsynaptic point where a single presynaptic bouton delivers its message. That picture is correct but incomplete, since it overlooks other neuronal elements surrounding each spine. Here we characterize that neighborhood for the first time by counting and measuring the proximity of the elements encircling each postsynaptic spine. We call this neighborhood the vicinome: the full set of neuronal and glial elements surrounding a dendritic spine. We used ground-truth three-dimensional meshes from the H01 petavoxel dataset, a reconstruction of the human cerebral cortex. We analyzed 4550 neighboring elements across 322 spines from 17 pyramidal neurons in cortical layers 2 through 5, with each spine classified as apical or basal. Neighbor number followed a depth gradient, falling from 17.2 {+/-} 4.2 elements per spine in layer 2 apical spines to 12.5 {+/-} 3.1 in layer 5 basal spines. A linear mixed model with a random intercept per neuron confirmed a strong effect of layer (p = 4.3 x 10-5) with large effect sizes (Cohen's d up to 1.45) and no effect of polarity. The minimum spine-to-neighbor distance stayed uniform, near 30 nm in every group, and although some depth-related contrasts were significant, all effect sizes were negligible (Cohen's d below 0.21). We conclude that cortical depth, and not pyramidal neuron polarity, was related to the number of neuronal elements neighboring the spine. We suggest that vicinome crowding could offer a measurable observable for comparison across regions, ages, species, and disease.

neuroscience↗

bioRxiv2026

Orientation-invariant morphometry reveals a continuum of dendritic spine forms in layer II pyramidal neurons of the petavoxel human connectome

A recent study (Manjarrez et al., 2026) showed that the classification of cortical dendritic spines into stubby, thin, and mushroom subtypes is unstable under rotation. That result criticizes the categorical scheme but leaves an open question. What is the actual structure of spine morphology once the viewing angle is controlled? Here we answer it. We analyzed 228 spines from layer II pyramidal neurons in the H01 nanometer-resolution reconstruction of human temporal cortex. We first quantified the source of instability. We found that rotating dendritic segments by 90 degrees about their axes shifted the apparent spine height and head width in opposite directions across the population, thereby confirming orientation-dependent measurement error. Furthermore, to obtain measurements free of this artifact, we developed the Spine Morphometry Hub (SMH), a 12-point anatomical landmark framework that characterizes each spine in all three orthogonal planes and extracts geometric, voxel-based, and mesh-based metrics. All morphometric distributions were unimodal and right-skewed. Density-based clustering assigned most spines to noise, and a Monte-Carlo test against a discrete two-type null model confirmed that this pattern is incompatible with categorical subtypes. We also confirmed that apical and basal spines were statistically indistinguishable. Unlike previous reports of a spine continuum, all based on orientation-dependent measurements, our framework removes the viewing-angle confound itself, so the continuum we observe cannot be attributed to a projection artifact. Hence, our framework will be useful to quantify dendritic-spine remodeling in neurological disorders, in which spine shape has long been observed but never measured against an orientation-invariant morphometric standard. HighlightsO_LISpine Morphometry Hub (SMH) measures spines free of viewing-angle error C_LIO_LISMH was validated as an orientation-invariant morphometry framework C_LIO_LIRotating dendrites by 90{degrees} shifts spine height and head width oppositely C_LIO_LIAll morphometric distributions are unimodal and right-skewed, not categorical C_LIO_LISMH could be used to quantify dendritic-spine remodeling in neurological disorders C_LI

neuroscience↗

bioRxiv2026

Rotating a petavoxel reconstruction exposes the viewing-angle bias inherent to Golgi-Cox and confocal dendritic-spine classification

Dendritic spines are the principal postsynaptic sites of excitatory transmission. For over a century, their shape has been sorted into discrete categories such as filopodia, thin, long thin, stubby, mushroom, and branched, largely by Golgi-Cox impregnation and, more recently, confocal microscopy. However, both approaches share a fundamental limitation. The histological sectioning and single-viewpoint imaging that these methods rely on cannot control the orientation of a spine relative to the observer. Because a spine is a three-dimensional object, the projection seen depends on how its parent dendrite lies within the section. Here, using the publicly available H01 petavoxel reconstruction of human temporal cortex imaged by serial-section electron microscopy (EM), we show that spine-shape classification depends strongly on viewing angle. A total of 445 spines on layer 4 basal dendrites of five pyramidal neurons were classified from an initial viewpoint (Angle 1), then reclassified after rotation in Neuroglancer (Angle 2). Only 20.9% kept their category, so chance-corrected agreement was negligible (Cohens kappa = 0.027). These observations provide direct evidence that the rigid Golgi-Cox and confocal taxonomies conflate true spine morphology with the arbitrary angle of view. Our results, therefore, support recasting spine shape as a three-dimensional continuum, measurable in petavoxel reconstructions such as H01 through free rotation in Neuroglancer. Significance statementThe classification of dendritic spines into discrete shape classes underpins a vast literature on synaptic plasticity, development, and disease. Yet it rests on two-dimensional images whose viewing angle is not controlled. By rotating the same human spines in a nanoscale EM reconstruction, this study shows that four out of five spines change category with viewpoint alone. The finding exposes a systematic bias in Golgi-Cox and confocal classifications. It argues that spine morphology should be treated as a measurable three-dimensional continuum rather than a set of fixed labels.

neuroscience↗

bioRxiv2023

Reduction of low-frequency oscillations in cerebral circulation correlates with pupil dilation during cognition: an fNIRS study

Numerous studies have utilized functional near-infrared spectroscopy (fNIRS) to investigate brain hemodynamics during diverse cognitive tasks. However, although these studies have consistently reported increased oxygenation levels in the prefrontal cortex, they have not explored their effects on the amplitude of brain low-frequency oscillations (LFO). Additionally, other reports have shown that pupil dilation occurs during cognitive tasks, which may indicate a correlation between LFO amplitude and pupil dilation. However, no study has demonstrated such a correlation. Our research has two aims: firstly, to analyze the impact of cognitive tasks on the amplitude of LFO using oxyhemoglobin (HbO2) fNIRS signals, and secondly, to assess the relationship between the amplitude of these LFO and pupil diameters during such cognitive tasks. We found that during arithmetic tasks, the brain LFOs recorded on the prefrontal cortex were temporarily reduced while pupil diameter increased. These findings offer new insights into the physiological functions of reactivity of LFO in cerebral circulation. Additionally, combining fNIRS signals to track LFO on the prefrontal cortex with pupil measurement shows the feasibility of developing efficient hybrid brain-computer interfaces of LFO-pupil detection capable of predicting the initiation and ending of cognitive processes. Significant statementInspired by the Berger effect, which demonstrates alpha wave reactivity with eye-opening, our study investigated reactivity in other physiological oscillations related to brain hemodynamics during cognition. Our findings revealed a novel phenomenon: a temporary reduction in the amplitude of low-frequency oscillations (LFOs) of oxyhemoglobin (HbO2) in the brains prefrontal cortex, concurrent with increased pupil diameter during arithmetic tasks. This discovery expands our knowledge of LFO in cerebral circulation and creates new avenues for studying fNIRS-LFO reactivity during cognitive tasks in healthy individuals and patients.

neuroscience↗

bioRxiv2023

Similarity index of ex-Gaussian reaction time signatures

In psychology and cognitive neuroscience, reaction time (RT) series and their ex-Gaussian distributions are commonly used to explore the time course of cognitive processes. This study investigated the hypothesis that successive triads of ex-Gaussian mu, sigma, and tau parameters of reaction-time variability across time can be used to construct a geometrical object we termed ex-Gaussian RT-signature, which could help characterize interindividual differences between congruent and incongruent stimuli. To test this hypothesis, we calculated the similarity index of these geometrical objects in young adult participants without detectable neurological disorders. Our findings show that each participant displayed distinct ex-Gaussian RT-signatures in a Cartesian 3D plot, thus exhibiting distinct psychophysical fingerprints. Furthermore, our results revealed that the ex-Gaussian RT-signatures for incongruent stimuli demonstrated a significantly higher similarity index across participants than congruent stimuli (p<0.001; Cohen d=0.4). We suggest that visualizing this psychophysical signature could serve as a valuable tool in characterizing differences in cognitive functioning between individuals, thus providing insights into the development of personalized medicine.

neuroscience↗