Biology subjects

Kermen, F.

Publications and source records attributed to Kermen, F..

6 recordsLinked to original sources

bioRxiv2026

SEROTONERGIC ANXIETY IS A STRESS INTENSITY-DEPENDENT STATE MEDIATED BY DOPAMINERGIC SIGNALING

Despite the central role attributed to serotonin in anxiety, its involvement and therapeutic efficacy are inconsistent, raising the possibility that serotonergic recruitment depends on the stress history from which anxiety emerges. Using larval zebrafish, we combined graded glucocorticoid exposure with chemogenetic DRN manipulation, whole-brain activity mapping, and pharmacology to test whether stress intensity determines serotonergic involvement in anxiety.Increasing stress intensity did not simply increase anxiety severity but generated distinct anxiety phenotypes. Lower glucocorticoid exposure produced context-general anxiety that required the serotonergic DRN, whereas higher exposure produced context-dependent, DRN-independent anxiety. Whole-brain mapping identified a posterior tubercular/hypothalamic dopaminergic region associated with DRN-dependent anxiolysis, while D1, but not D2 receptor antagonism abolished the anxiolytic effect of DRN ablation. Finally, environmentally relevant nanomolar concentrations of methylphenidate reduced anxiety-like behavior, further supporting dopaminergic modulation of anxiety. Together, our findings identify stress intensity as a determinant of serotonergic recruitment during anxiety, reveal a downstream contribution of D1-dependent dopaminergic signaling, and provide a framework for understanding the mechanistic heterogeneity of anxiety and its variable response to serotonergic treatments.

neuroscience↗

bioRxiv2026

Organization, development, and plasticity of the serotonergic dorsal raphe nucleus projectome

The dorsal raphe nucleus (DRN) is the main source of serotonin (5-HT) in the central nervous system. 5-HT DRN neurons modulate a wide range of physiological functions and brain states via their widespread and heterogeneous projections. Yet the organizational logic, developmental dynamics, and experience-dependent plasticity of these projections remain poorly understood. By reconstructing the whole brain projections of 81 individual 5-HT DRN neurons across developmental stages in the larval zebrafish, we find that these neurons exhibit diverse projection patterns, ranging from broadly distributed to spatially confined. We identify two previously uncharacterized, projection-defined subpopulations within the larval dorsal raphe nucleus, which selectively target either the telencephalon or the spinal cord. This organization is consistent with the existence of anatomically distinct serotonergic pathways that may differentially influence forebrain and sensorimotor circuits. Longitudinal analysis revealed that the gross architecture of 5-HT neurons remained stable during larval development, although region-specific remodeling occurred in all neurons. Importantly, stress exposure during the first week of development, but not thereafter, altered the density of 5-HT DRN projections to telencephalic regions, suggesting a critical window of increased plasticity during early life. Collectively, our findings clarify the developmental trajectory, maturation, and stress-induced plasticity of the serotonergic circuitry, providing important insights for deciphering the pathophysiology of stress-related mental disorders.

neuroscience↗

bioRxiv2025

Early life chronic stress-disrupted activity of the dorsal raphe nucleus selectively drives behavioral impairments

Stress elicits variable systemic and neural changes in vertebrates, with outcomes ranging from adaptive to pathological. Several studies have implicated the dorsal raphe nucleus (DRN), a brainstem nucleus containing a heterogeneous population of serotonergic (5-HT) neurons, in the adaptive stress response and the pathological changes resulting from chronic stress. However, it is not known whether early life chronic stress affects the developing DRN activity, or whether the stress-induced changes affect 5-HT DRN neurons in a subregion- or phenotype-specific manner. To answer these questions, we used in vivo 2-photon calcium imaging of 5-HT DRN neurons in larval zebrafish exposed to chronic unpredictable stress during early life. We found that early life chronic stress prevented the normal habituation of the serotonergic system to a repeated acute stressor by altering the balance of excitatory/inhibitory responses within the DRN. Interestingly, these changes were most pronounced in a subset of stress-vulnerable serotonergic cells co-expressing GABAergic markers. Further, using chemogenetic ablation of 5-HT DRN neurons, we showed that stress-induced plasticity of the DRN contributed to changes in startle response habituation and in locomotive activity, but not in anxiety-like behaviors. Collectively, our results emphasize the role of stress-induced plasticity of DRN neurons in the selective regulation of maladaptive behavioral outcomes.

neuroscience↗

bioRxiv2020

Neural dysfunction at the upper thermal limit in the zebrafish

Understanding the physiological mechanisms that limit animal thermal tolerance is crucial in predicting how animals will respond to increasingly severe heatwaves. Despite its importance for understanding climate change impacts, these mechanisms underlying the upper thermal tolerance limits of animals are largely unknown. It has been hypothesised that the upper thermal tolerance in fish is limited by the thermal tolerance of the brain and that it is ultimately caused by a global brain depolarization. In this study, we developed methods for measuring the upper thermal limit (CTmax) in larval zebrafish (Danio rerio) with simultaneous recordings of brain activity using GCaMP6s calcium imaging in both free-swimming and agar-embedded fish. We discovered that during warming, CTmax precedes, and is therefore not caused by, a global brain depolarization. Instead, the CTmax coincides with a decline in spontaneous neural activity and a loss of neural response to visual stimuli. By manipulating water oxygen levels, we found that oxygen availability during heating affects both locomotor-related neural activity, the neural response to visual stimuli, and CTmax. Our results suggest that the mechanism limiting the upper thermal tolerance in zebrafish larvae is reduced oxygen availability causing impaired brain function.

neuroscience↗

bioRxiv2019

Investigating olfactory behaviors in adult zebrafish

Odor-driven behaviors such as feeding, mating and predator avoidance are crucial for animal survival. While the zebrafish olfactory circuitry is well understood, a comprehensive description of odor-driven behaviors is needed to better relate olfactory computations to animal responses. Here, we used a medium-throughput setup to measure the swimming trajectories of 10 zebrafish in response to 17 ecologically relevant odors. By selecting appropriate locomotor metrics, we constructed ethograms systematically describing odor-induced changes in the swimming trajectory. We found that fish reacted to most odorants, using different behavioral programs and that combination of few relevant behavioral metrics enabled to capture most of the variance in these innate odor responses. We observed that monomolecular odors in similar chemical categories were weakly clustered based on the behavioral responses, likely because natural odors elicited stronger reactions than the monomolecular odors. Finally, we uncovered a previously undescribed intra and inter-individual variability of olfactory behaviors and suggest a small set of odors that elicit robust responses. In conclusion, our setup and results will be useful resources for future studies interested in characterizing olfactory responses in aquatic animals.

animal behavior and cognition↗

bioRxiv2019

Interhemispheric connections between olfactory bulbs improve odor detection

Interhemispheric connections enable interaction and integration of sensory information in bilaterian nervous systems and are thought to optimize sensory computations. However, the cellular and spatial organization of interhemispheric networks as well as the computational properties they mediate in vertebrates are still poorly understood. Thus, it remains unclear to which extent the connectivity between left and right brain hemispheres participates in sensory processing. Here, we show that the zebrafish olfactory bulbs (OBs) receive direct interhemispheric projections from their contralateral counterparts in addition to top-down inputs from the contralateral zebrafish homolog of olfactory cortex. The direct interhemispheric projections between the OBs reach peripheral layers of the contralateral OB and retain a fine-grained topographic organization, which directly connects similarly tuned olfactory glomeruli across hemispheres. In contrast, interhemispheric top-down inputs consist of diffuse projections that broadly innervate the inhibitory granule cell layer. Jointly, these interhemispheric connections elicit a balance of topographically organized excitation and non-topographic inhibition on the contralateral OB and modulate odor responses. We show that the interhemispheric connections in the olfactory system enable the modulation of odor response and improve the detection of a reproductive pheromone, when presented together with competing complex olfactory cues, by boosting the response of the pheromone selective neurons. Taken together, our data shows a previously unknown function for an interhemispheric connection between chemosensory maps of the olfactory system.

neuroscience↗