Biology subjects

Lemus, L.

Publications and source records attributed to Lemus, L..

9 recordsLinked to original sources

bioRxiv2026

Abstract Encoding of Sounds in the Frontopolar Cortex

The frontopolar cortex has been linked to higher-order cognition, including analogical reasoning, cost-benefit analysis, and semantic associations, primarily based on neuroimaging studies in humans rather than from direct single-neuron recordings. Notably, sensory input to this region originates from auditory cortical areas. To investigate the role of the frontopolar cortex in auditory perception, we recorded single neurons in nonhuman primates trained to discriminate between various sounds, including monkey calls and human words. We found that individual neurons form abstract, nonlinear representations of learned and novel sounds, collectively encoding all sound categories and generating decision-making signals. Our findings suggest that the frontopolar cortex integrates auditory information into behaviorally relevant signals, thereby providing insights regarding its role in cognition.

neuroscience↗

bioRxiv2025

The lectin Emp47/ERGIC-53 targets misfolded O-mannosylated ER proteins to ERAD

The yeast bifunctional O-mannosyltransferase complex Pbn1-Gpi14 generates endoplasmic reticulum (ER)-associated degradation (ERAD) signals by O-mannosylating misfolded ER proteins, but how these signals are recognized is unknown. To address this question, we identified the binding partners of Pbn1 and found that the ER lectins Emp47 (ERGIC-53 in mammals) and Emp46 were among the strongest interactors. Simultaneous deletion of Emp46 and Emp47, but not of Yos9, impaired ERAD of an O-mannosylated, N-glycan-deficient CPY* variant. ERAD was restored by plasmid-expressed Emp47, but not by a mutant lacking its carbohydrate-recognition domain (CRD). Furthermore, we show that Emp47 interacts physically with the Hrd1 complex. Together, our data support a model in which Emp47 both recognizes O-mannoses on misfolded proteins and targets them to ERAD.

cell biology↗

bioRxiv2025

ER-associated degradation relying on protein O-mannosylation

Protein quality control in the secretory pathway, whose dysfunction is linked to various human diseases, begins in the endoplasmic reticulum (ER) and involves ER-associated degradation (ERAD) of terminally misfolded species. We have addressed the roles of protein O-mannosylation in ERAD using complementary genome-wide screens in yeast. Our findings reveal that protein O-mannosylation by the conserved ER-resident O-mannosyltransferase complex Pbn1-Gpi14 generates ERAD cues. This mechanism participates in regulating ERAD of substrates that contain serine-rich regions and provides a fail-safe mechanism for the degradation of non-N-glycosylated misfolded proteins. Our data suggest that the de novo synthesis of ERAD cues through protein O-mannosylation is an essential component of ER quality control.

cell biology↗

bioRxiv2024

Invariant crossmodal equivalence between objects in rhesus monkeys

After hearing the words Little Red Riding Hood, many humans instantly visualize a girl wearing a red hood in the woods. However, whether nonhuman primates also evoke such visual imagery from sounds remains an open question. We explored this from direct behavioral measurements from two rhesus macaques trained in a delayed crossmodal equivalence task. In each trial, they listened to a sound, such as a monkey vocalization or a word, and three seconds later, selected a visual equivalent out of a pool of 2 to 4 pictures appearing on a touchscreen. We show that monkeys can be trained to discriminate perceptual objects of numerous properties and furthermore that they perceive as invariant different versions of the learned sounds. We propose two potential mechanisms for the brain to solve this task: acoustic memory or visual imagery. After analyzing the monkeys choice accuracies and reaction times in the task, we find that they experience visual imagery when listening to sounds. Therefore, the ability of rhesus monkeys to perceive crossmodal equivalences between learned categories poses rhesus monkeys as an ideal model organism for studying high-order cognitive processes like semantics and conceptual thinking at the single-neuron level.

animal behavior and cognition↗

bioRxiv2023

Crossmodal correspondence of natural amplitude modulations

Crossmodal correspondence is the ability to recognize objects from different sensory modalities to be similar. Here, we investigated the capacity of humans to perform crossmodal discriminations between visual, acoustic, and tactile stimuli modulated in amplitudes of low-pass filtered envelopes obtained from natural sounds. We found that the perception of crossmodal correspondence emerged from the number of amplitude prominences in each stimulus rather than from temporal variations. Therefore, we propose saliency as the supramodal trade coin of temporal modulations.

neuroscience↗

bioRxiv2020

Neuronal Correlates of the Perceptual Invariance of Words and Other Sounds in the Supplementary Motor Area of Macaques

The supplementary motor area (SMA) of the brain is critical for integrating memory and sensory signals into perceptual decisions. For example, in macaques, SMA activity correlates with decisions based on the comparison of sounds.1 In humans, functional MRI shows SMA activation during the invariant recognition of words pronounced by different speakers.2 Nevertheless, the neuronal correlates of perceptual invariance are unknown. Here we show that the SMA of macaques associates novel sounds with behaviors triggered by similar learned categories when recognizing sounds such as words. Notably, the neuronal activity at single and population levels correlates with the monkeys behaviors (e.g. hits and false alarms). Our results demonstrate that invariant recognitions of complex sounds involve premotor computations in areas other than the temporal and parietal speech areas. Therefore, we propose that perceptual invariance depends on motor predictions and not only sensory representations. We anticipate that studies on speech will observe sensory-motor transformations of acoustic information into motor skills.

neuroscience↗

bioRxiv2020

Auditory Decisions in the Supplementary Motor Area

In human speech and communication across various species, recognizing and categorizing sounds is fundamental for the selection of appropriate behaviors. But how does the brain decide which action to perform based on sounds? We explored whether the premotor supplementary motor area (SMA), responsible for linking sensory information to motor programs, also accounts for auditory-driven decision making. To this end, we trained two rhesus monkeys to discriminate between numerous naturalistic sounds and words learned as target (T) or non-target (nT) categories. We demonstrated that the neural population is organized differently during the auditory and the movement periods of the task, implying that it is performing different computations in each period. We found that SMA neurons perform acoustic-decision-related computations that transition from auditory to movement representations in this task. Our results suggest that the SMA integrates sensory information while listening to auditory stimuli in order to form categorical signals that drive behavior.

neuroscience↗

bioRxiv2019

Invariant recognition of words and naturalistic sounds in non-human primates

The ability to invariably identify spoken words and other naturalistic sounds in different temporal modulations and timbres requires perceptual tolerance to numerous acoustic variations. However, the mechanisms by which auditory information is perceived to be invariant are poorly understood, and no study has explicitly tested the perceptual constancy skills of nonhuman primates. We investigated the ability of two trained rhesus monkeys to learn and then recognize multiple sounds that included multisyllabic words. Importantly, we tested their ability to group unexperienced sounds into corresponding categories. We found that the monkeys adequately categorized sounds whose formants were at close Euclidean distance to the learned sounds. Our results indicate that macaques can attend and memorize complex sounds such as words. This ability was not studied or reported before and can be used to study the neuronal mechanisms underlying auditory perception.

neuroscience↗

bioRxiv2019

A post-ER degradation pathway that relies on protease-dependent internalization from the vacuolar membrane

Newly synthesized proteins of the secretory pathway are quality-controlled inside the endoplasmic reticulum (ER) and, if not properly folded, are retained. An exception are glycosylphosphatidylinositol-anchored proteins (GPI-APs) which can leave the ER even when misfolded and are routed to the vacuole/lysosome for degradation by largely unknown mechanisms linked to post-ER quality control. Using yeast as model organism, we show that Gas1*, an ER-exported misfolded GPI-AP, is diverted from the secretory pathway to endosomes for transport to the vacuole. However, Gas1* is not sorted into endosomal intraluminal vesicles but internalizes directly from the vacuolar membrane. There, the vacuolar protease Pep4, but not any other known vacuolar protease, is required for Gas1* internalization. Our data reveal novel and unexpected mechanisms for invaginations from the vacuolar membrane.\n\nHighlightsO_LIER-exited misfolded GPI-anchored proteins are routed to the vacuole via endosomes but do not internalize into intraluminal vesicles\nC_LIO_LIInternalization occurs directly from the vacuolar membrane into intravacuolar mobile structures\nC_LIO_LIInternalization from the vacuolar membrane depends on the proteolytic activity of the vacuolar protease Pep4\nC_LI

cell biology↗