Biology subjects

Talpir, I.

Publications and source records attributed to Talpir, I..

4 recordsLinked to original sources

bioRxiv2026

Thalamo-insular basis for updating physiological needs

Physiological needs, such as thirst and hunger, produce powerful motivation for behaviors that are essential for survival. Yet, how the brain estimates these needs remains unknown. It is unclear whether the brain continuously monitors bodily signals to create real-time representations, or if existing internal representations are only updated when meaningful changes occur. To address this question, we manipulated thalamic internal sensory inputs to the interoceptive insular cortex. We found that inhibiting internal sensory inputs prevents the updating of insular cortex representations of thirst and hunger, thereby keeping its activity closer to its initial physiological need state. Consequently, cued feeding and drinking, as well as free consumption of food and water, persist beyond the current physiological need. We further show that insular cortex activity normally represents both predictions and sensory information. However, violating learned expectations evokes widespread need-specific prediction error signals. Our results thus reveal a thalamo-cortical basis for updating physiological needs in the brain.

neuroscience↗

bioRxiv2026

Simple baselines rival protein language models in mutation-dense design tasks

Computational protein design demands generally applicable models that reliably predict or generate unmeasured variants with superior functional properties. Although protein language models (pLMs) have been used in zero-shot and transfer-learning design studies, they have generally not been assessed in benchmarks that explicitly test combinatorial extrapolation from lower- to higher-order variants. Here we benchmark widely used pLMs against conventional baseline methods in recently described dense, experimentally validated multi-mutant landscapes. We find that regardless of architecture and parameter count, pLMs are statistically similar to one another, and none consistently outperforms conventional baseline methods. Furthermore, their ability to distinguish functional from non-functional variants in zero-shot prediction is comparable to that of conventional homology-based methods. We suggest that to contribute significantly to the design of protein function, pLMs may need to encode biophysical and structural priors or be combined with structure-based approaches.

bioinformatics↗

bioRxiv2026

A cortical basis for perception of internal gut sensations

Interoception, the sensing of internal bodily signals, is essential for brain-body interactions and shapes emotion, cognition, and behavior1-5. Subconscious internal signals, including heartbeats or stomach fullness, can rise to conscious awareness, and this process can improve with practice, as seen in meditation, mindful eating, or toilet training in early infancy. Conversely, disrupted interoception is emerging as a common deficit in diverse psychiatric disorders1,3,6,7. Nevertheless, we still lack a fundamental understanding of the neurobiological basis of perception and conscious reporting of internal sensations. Here, we combine genetic and ultra-sensitive optogenetic tools in mice to establish a quantitative framework for studying internal perception. We developed a behavioral task in which mice report detecting non-invasive optogenetic activation of gut mechanosensory neurons, establishing "interoceptive psychophysics". We combine this approach with cellular-resolution imaging and manipulations to reveal the neuronal basis for perception of these internal gut sensations in the interoceptive insular cortex. While representations of sensory stimuli were consistently observed in insular cortex across different tasks, we found that perceptual reports were only encoded during a more difficult psychophysics task, but not during basic detection. Accordingly, manipulation of insular cortex activity affected behavioral reports only in the psychophysics task. These findings reveal a neural basis for perception of internal gut sensations and provide a blueprint for future quantitative exploration of other interoceptive modalities.

neuroscience↗

bioRxiv2023

Stereotyped goal-directed activity patterns in the insular cortex

The insular cortex is involved in diverse processes including bodily homeostasis, emotions, and cognition. Yet we lack a comprehensive understanding of how it processes information at the level of neuronal populations. We leveraged recent advances in unsupervised machine learning to study insular cortex population activity patterns (i.e., neuronal manifold) in mice performing goal-directed behaviors. We find that the insular cortex activity manifold is remarkably consistent across different animals and under different motivational states. Activity dynamics within the neuronal manifold are highly stereotyped during rewarded trials, enabling robust prediction of single-trial outcomes across different mice, and across various natural and artificial motivational states. Comparing goal-directed behavior with self-paced free consumption, we find that the stereotyped activity patterns reflect task-dependent goal-directed reward anticipation, and not licking, taste, or positive valence. These findings reveal a core computation in insular cortex that could explain its involvement in pathologies involving aberrant motivations.

neuroscience↗