Biology subjects

Stefaniuk, M.

Publications and source records attributed to Stefaniuk, M..

4 recordsLinked to original sources

bioRxiv2026

Deep Phenotyping with Global Brain Activity and Plasticity Mapping Identify the Dorsal Raphe-Basolateral Amygdala Circuit as a Mediator of Adaptive Stress Responses

Exposure to chronic environmental challenges triggers divergent behavioral trajectories across individuals. At the core, these different trajectories can be classified as individuals actively adapting to the challenges ("responders") and those displaying a rigid, non-responsive phenotype ("non-responders"). The brain system-wide network configurations that dictate why individuals diverge along these differential coping strategies, which can also lead to disease vulnerability or resilience, remain poorly understood. Here, we paired machine-learning-based deep behavioral phenotyping with multi-modal whole-brain imaging, integrating longitudinal Manganese-Enhanced MRI (MEMRI) and post-challenge cFOS mapping, to chart the functional landscape of individual stress trajectories in mice subjected to chronic social defeat stress. High-dimensional behavioral phenotyping revealed that active stress adaptation is a complex trajectory marked by latent, pre-stress kinetic signatures in vigilance-like and locomotive behaviors. At the neural level, longitudinal MEMRI captured distinct, consolidated activity reconfigurations across canonical valence and stress-regulatory circuits that segregated responders from non-responders. Complementary whole-brain cellular cFOS network analysis after an additional acute challenge revealed that non-responders exhibited marked hyper-modularity and network fragmentation, whereas responders feature a tightly integrated functional module co-clustering the periaqueductal gray, ventral tegmental area, basolateral amygdala (BLA), and dorsal raphe (DR). Notably, functional network connectivity along the DR-BLA axis was completely lost in non-responsive animals. Finally, pathway-specific chemogenetic inhibition of BLA-projecting DR neurons during a social challenge significantly attenuated social avoidance and reversed anxiety-like behavioral deficits, effectively shifting active behavioral adaptation toward a non-responsive phenotype. Together, these findings demonstrate that individual stress-coping strategies are driven by coordinated, system-wide reconfigurations of activity and plasticity, identifying the DR-BLA circuit as a critical gatekeeper of adaptive stress responses. Graphical AbstractGlobal neural functional alterations defining responding vs non-responding populations following chronic stress are understudied, yet crucial. Deep phenotyping followed by mapping brain-wide activity and plasticity changes identified these underlying divergent functional networks. Acute manipulation of a dorsal raphe - basolateral amygdala pathway ameliorated adaptive stress responses, highlighting the significance of this network-based approach. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/740522v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1850a04org.highwire.dtl.DTLVardef@1549284org.highwire.dtl.DTLVardef@15f3ebforg.highwire.dtl.DTLVardef@107ca9_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

Doubling the Field of View in Common-Path Digital Holographic Microscopy via Wavelength Scanning and Polarization Gratings

Digital holographic microscopy systems in a common-path configuration, compared to systems with a separate reference arm, offer a compact design and resistance to disturbances. They can operate with partially coherent illumination, reducing speckle noise. However, they are limited by the overlapping of the object beam and its laterally shifted replica. As a result, images from different regions of the object overlap on the detector, preventing imaging of dense samples. We present the wavelength-scanning replica-removal method, which solves this problem by enabling the separation of information from both replicas and thereby doubling the effective field of view (FOV). The wavelength-scanning multi-shear replica removal algorithm plays a key role in reconstructing the undisturbed phase from a series of holograms recorded with variable shears. The shear value is controlled by changing the illumination wavelength. This enabled the development of two measurement modes: time-domain wavelength scanning for high-quality imaging, and a single-shot mode with frame division into color channels to improve temporal resolution. The method was validated using resolution tests and biological samples - neurons and dynamic yeast cultures. By combining the advantages of the common-path configuration with dense-structure imaging and dynamic processes, the proposed method constitutes a versatile tool for quantitative phase microscopy.

biophysics↗

bioRxiv2022

Activation of trace amine-associated receptor 1 (TAAR1) reduces alcohol drinking behaviors in mice

Alcohol dependence is characterized by the abnormal release of dopamine in the brain reward-related areas. Trace amine-associated receptor 1 (TAAR1) is a G Protein-Coupled Receptor that negatively regulates dopamine neurotransmission and thus is a promising target in the treatment of drug addiction. However, the role of TAAR1 in the regulation of alcohol abuse remains understudied. Here, we assessed the effect of TAAR1 activation on alcohol-drinking behaviors of C57Bl/6J female mice housed in IntelliCages. The animals were administered with either vehicle or TAAR1 full selective agonist, RO5256390, and tested for alcohol consumption, alcohol preference, and motivation for alcohol seeking. We found that mice with the highest preference for alcohol (high drinkers) in the RO5256390 group consumed less alcohol and had lower alcohol preference in comparison to high drinkers in the vehicle group, during 20 h of free alcohol access (FAA). We also found decreased alcohol consumption and alcohol preference comparing all animals in the RO5256390 to all animals in the vehicle group, during 20 h of FAA performed after the abstinence. These effects of RO5256390 lasted for the first 24 hours after administration that roughly corresponded to the compound level in the brain, measured by mass spectrometry. Finally, we found that administration of RO5256390 may attenuate motivation for alcohol seeking. Taken together, our findings reveal that activation of TAAR1 may transiently reduce alcohol drinking; thus, TAAR1 is a promising target for the treatment of alcohol abuse and relapse.

animal behavior and cognition↗

bioRxiv2021

A whole-brain imaging-based systems approach to understand origin of addiction in binge-like drinking model

Many fundamental questions on addiction development are still unanswered. These questions are frequently difficult to address by examining a single brain structure, but can best be addressed at the systems level. Neurons create functional networks that change over time, since brain regions may work together differently in different contexts. We offer a framework for describing the nature behind alcohol binge drinking and the transition to addiction. The present study investigated whole-brain c-Fos expression following reexposure to alcohol in a model of binge-like drinking in mice in IntelliCage. We developed a dedicated image computational workflow to identify c-Fos-positive cells in three-dimensional images obtained after optical tissue clearing and whole-brain imaging in the light-sheet microscope. We analyzed functional networks and brain modularity following reexposure to alcohol. c-Fos levels in brains from animals that were reexposed to alcohol were clearly different from binge drinking animals. Structures involved in reward processing, decision making and characteristic for addictive behaviors stood out particularly. In alcohol reexposed animals differently active structures either gained or lost correlation when compared to the control group.

neuroscience↗