Biology subjects

Demarchi, L.

Publications and source records attributed to Demarchi, L..

6 recordsLinked to original sources

bioRxiv2026

Single-cell map of the female brain across reproductive transitions

Ovarian hormone shifts enable reproduction and are associated with substantial brain plasticity and disease risks. While imaging studies provide (micro)structural insights into brain changes across the ovarian cycle and pregnancy, the high resolution, single-cell map of the brain across reproductive transitions is missing. Here, we performed multiome (gene expression and chromatin accessibility) analysis of the mouse ventral hippocampus (vHIP) across sex, estrous cycle, and peripartum period at single cell resolution. We identify dynamic changes in vHIP cellular composition across the estrous cycle and pregnancy, including in the neural stem cells of the dentate gyrus (DG), enabling hormone-driven neurogenesis. Major gene expression changes are neuronal function-relevant, cell type-specific, and found in excitatory neurons of CA1, CA3, and DG subfields, across sex and reproductive transitions. In contrast, chromatin accessibility changes are more extensive and found across cell types, likely driven by estrogen level shifts in both within-female and between-sex comparisons. We show that chromatin remodeling during the estrous cycle primes the genome for gene expression changes during pregnancy and is also enriched for brain disease-relevant genes. Finally, we reveal a thyroid hormone transporter (Transthyretin, Ttr) gene as the major candidate gene that drives structural and behavioral changes across the estrous cycle and pregnancy. Our study provides an extensive cellular and molecular view of how reproductive transitions shape the brain and opens the possibility to target downstream targets of estrogen, including thyroid hormone signaling, as a treatment option for hormone-sensitive periods in women.

neuroscience↗

bioRxiv2025

A logarithmic theory of visuomotor stabilization

Although many animals rely on visual information to navigate, optic flow is inherently ambiguous as it confounds information about motion speed and object distance. As a result, the visual feedback produced by a given motor command is context-dependent and requires an appropriately adapted response. Recent experiments have investigated how the fish Danionella cerebrum use visual cues to stabilize their position against simulated external currents. Logarithmic sensorimotor transformations have been proposed to enable adaptive responses to perturbations while preventing delay-induced instabilities. Here, we develop the theoretical framework introduced for continuous locomotion to show how logarithmic coding naturally gives rise to this adaptive behavior. The system is modeled by a nonlinear delay differential equation, which is analyzed using dynamical systems theory. We further analyze experimental data to uncover the mechanisms underlying swimming initiation and positional drift correction. Finally, we extend our framework to intermittent locomotion, resulting in a nonlinear difference equation, and show that it still produces robust adaptive behavior. This is motivated by the literature on zebrafish, where visuomotor stabilization has been extensively studied, but burst-and-coast swimming obscures the underlying adaptation mechanism. We show that our theory can reproduce the experimental results reported for motor adaptation in zebrafish without invoking internal models. Overall, our results highlight logarithmic coding as a unifying principle for visuomotor stability across continuous and intermittent locomotor regimes.

neuroscience↗

bioRxiv2025

A sensorimotor instability drives a locomotor transition during fish development

Animals rely on movement to survive -- to explore their environment, find food and mates and avoid danger. During development, changes in body shape, muscle strength and physiological needs drive the continuous adjustment of locomotor patterns. How these changes are orchestrated in a flexible and adaptive manner remains unknown. We explore this question in Danionella cerebrum, a miniature freshwater fish that is emerging as an important vertebrate model in systems neuroscience. We identify a clear transition in locomotion, from continuous to burst-and-coast swimming occurring around 3 weeks of age. We demonstrate that this transition is an energy saving strategy, and that it reflects an insta-bility in the sensorimotor process governing speed regulation. Rather than a preprogrammed developmental switch, it is therefore directly tied to the animal swimming strength. We confirmed this finding by manipulating sensory feedback in order to induce a similar transition at fixed developmental stages. Together, our results illustrate a dynamic interplay between body, brain, and environment during development, offering new insights into the principles governing adaptive locomotion.

biophysics↗

bioRxiv2025

Logarithmic coding leads to adaptive stabilization in the presence of sensorimotor delays

Animals respond to sensory stimuli with motor actions, which in turn generate new sensory inputs. This sensorimotor loop is constrained by time delays that impose a trade-off between responsiveness and stability. Additionally, as the relationship between a motor command and the corresponding sensory feedback is context-dependent, the response must be adapted in real time. It is generally believed that this adaptation process relies on an internal model that is continuously updated through prediction error minimization. Here, we experimentally reveal an alternative strategy based on a simpler feedback mechanism that does not require any internal model. We developed a virtual reality system for the miniature transparent fish Danionella cerebrum that enables in vivo brain-wide imaging during fictive navigation. By systematically manipulating the feedback parameters, we dissected the motor control process that allows the animal to stabilize its position using optic flow. The sensorimotor loop can be fully described by a single delay differential equation, whose solutions quantitatively capture the observed behavior across all experimental conditions. Both behavioral and neural data indicate that the observed adaptive response arises from the logarithmic nonlinearities at the sensory (Weber-Fechner law) and motor (Hennemans size principle) ends. These fundamental properties of the nervous system, conserved across species and sensory modalities, have traditionally been interpreted in terms of efficient coding. Our findings unveil a distinct functional role for such nonlinear transformations: ensuring stability in sensorimotor control despite inherent delays and sensory uncertainty.

neuroscience↗

bioRxiv2025

Long-term offspring loss in lactating rats: Neurobiological and emotional consequences in a novel animal model

The maternal bond is a vital social connection that supports the survival and well-being of both the caregiver and offspring. Disruption of this bond, particularly following offspring loss, can result in profound trauma with long-lasting consequences. While considerable research has focused on the impact of maternal separation on offspring development, the biological effects of offspring loss on the mother remain largely unexplored. In this study, we examined the long-term effects of offspring loss on neuroplasticity, the oxytocin (OXT) and corticotropin-releasing factor (CRF) systems, and stress-coping behaviors in Sprague-Dawley rat mothers. We examined two groups of lactating mothers: (I) a control group, in which dams remained with their pups until natural weaning, and (II) a separated group, in which all offspring were removed on lactation day 1 and the mothers experienced offspring loss until the time corresponding to weaning (19 days). Our results reveal that pup removal increased OXT receptor binding and reduced dendritic spine density in limbic brain regions, without altering estrogen receptor or calbindin cell expression. Separated mothers additionally showed elevated plasma corticosterone levels and increased passive stress-coping behaviors in the forced swim test. Remarkably, passive stress-coping behavior was rescued by central CRF receptor blockade but not by OXT treatment, indicating that the CRF system plays a central role in the distress response to offspring loss. These findings establish the rat as a novel animal model for maternal distress, provide new insights into the complex neurobiology of grief, and suggests potential directions for future studies.

neuroscience↗

bioRxiv2024

Pup defence in lactating rats: The underlying neuropeptide signalling and their interactions in the nucleus accumbens shell

Maternal aggression is a core feature of rodent maternal behaviour to defend their offspring from potential threats and is modulated by corticotropin-releasing factor (CRF) and oxytocin (OXT) systems signalling. Here, we investigated the involvement of those neuropeptide systems in maternal aggression within the nucleus accumbens shell (NAcSh), a central region of the reward and maternal circuits. Infusion of CRF or Urocortin3 (CRF-receptor 2 agonist), as well as an OXT receptor antagonist, reduced maternal aggression, suggesting a role in pup defence. Furthermore, the effects of CRF infusion in the NAcSh continued beyond the maternal defence test (MDT), reducing nursing and increasing self-grooming. Corroborating the involvement of the stress system in maternal aggression, colocalization of CRF and cFos immunoreactive cells were increased in response to the MDT, regardless of pup presence. In addition, MDT exposure increased intra-NAc OXT release in lactating rats, which could be also triggered by local retrodialysis of CRF, but not Urocortin3. However, both ligands of the CRF system elicited dopamine (DA) release in different dynamics. Crh-r1 were predominantly expressed in the medial NAc on medium-sized spiny neurons (MSN), but also in the rostral part on GABAergic interneurons. Crh-r2 were mainly expressed in the rostral NAc and its expression on GABAergic interneurons increased towards the caudal pole. Lastly, we identified CRF-enriched projections to the NAcSh descending from the prefrontal cortex, the amygdala, and the paraventricular thalamus, among others. In conclusion, intra-NAcSh dampened CRF system activity and enhanced OXT system transmission are indispensable for successful pup defence. Any perturbations like increased CRF system signalling might activate compensatory mechanisms to ensure adequate maternal behaviour.

neuroscience↗