Biology subjects

Hesen, R.

Publications and source records attributed to Hesen, R..

3 recordsLinked to original sources

bioRxiv2025

Increased cocaine self-administration and prefrontal cortical dysregulation of glutamatergic and GABAergic signaling in a rat model for sensory processing sensitivity

While all organisms are tuned to the environment, some are more sensitive than others. In humans, this is reflected by the trait sensory processing sensitivity (SPS), comprising 20-30% of the population, which is characterized by heightened emotional reactivity, deeper information processing, greater awareness of their environment, and susceptibility to overstimulation. It is expected but unproven that high SPS increases the risk for psychostimulant use. To clarify this, we selected Wistar rats on behavioral extremes related to SPS and subjected them to isolation, neutral, and enriched housing conditions, followed by cocaine self-administration (S/A). Subsequently, we investigated neurobiological differences in excitatory/inhibitory neurotransmission of the low- and high SPS-like rats by evaluating key glutamatergic and GABAergic proteins in the infralimbic (ILc) and prelimbic (PLc) subregions of the prefrontal cortex. High SPS-like rats displayed higher cocaine intake during 1h S/A training sessions in isolated versus social conditions, whereas low SPS-like rats showed similar intake across housing conditions. During 6h S/A sessions, high SPS-like rats displayed a higher cocaine intake regardless of housing and greater motivation for cocaine under a progressive ratio scheme. High SPS-like cocaine-naive rats exhibited lower expression of glutamatergic and GABAergic markers in ILc and PLc compared to low SPS-like cocaine-naive rats. The opposite occurred after cocaine exposure: low and high SPS-like rats showed lower and higher expression levels, respectively, compared to naive counterparts. In conclusion, these findings suggest that a high SPS-like trait with associated glutamatergic and GABAergic alterations might be a risk factor for the development of cocaine use disorder.

neuroscience↗

bioRxiv2025

Different Sensitivity to Ethanol and Sucrose in DAT and SERT Knockout Rats

BackgroundDopamine and serotonin are key regulators of reward sensitivity, yet their distinct roles in motivating natural (e.g., sucrose) versus drug (e.g., ethanol) rewards remain unclear. Understanding these mechanisms could help explain individual variability in reward processing relevant to substance use vulnerability. MethodsWe assessed reward sensitivity in dopamine transporter (DAT) and serotonin transporter (SERT) knockout (KO) rats using both home cage (two-bottle choice for sucrose and ethanol) and operant paradigms (Pavlovian and instrumental learning). ResultsDAT KO rats showed lower sucrose preference (-27% for 2%, -13% for 4%) and intake (-42% for 4%), diminished Pavlovian responding for sucrose (-68%), and slower acquisition of sucrose-taking behavior ([~]+30 days) compared to WT rats. DAT KO rats also showed reduced ethanol preference in the home cage (-16%) despite an unchanged intake. Furthermore, operant performed was markedly reduced operant performance after the sucrose-to-ethanol transition (-83%), with no increase in ethanol-taking following sucrose exposure (0% change), unlike WT controls (+41%). SERT KO rats presented reduced sucrose preference (-5%) and intake (-46%) for the 4% solution only. In addition, SERT KO rats also showed reduced Pavlovian sucrose responding (- 28%) and slower acquisition of sucrose-taking ([~]+30 days) but intact responding and learning for ethanol. In the home cage, they displayed lower ethanol preference (-35%) without significant change in operant ethanol performance. A modest overall increase in ethanol-taking was seen post-sucrose in both SERT KO and WT, but without genotype-specific effects. Conclusion and ImplicationsDAT deletion broadly impaired sensitivity for both natural sucrose and ethanol rewards, particularly under effortful or devalued conditions. In contrast, SERT deletion produced more selective impairments by disrupting sucrose operant responding and moderately reducing ethanol reward preference. These findings reveal distinct but overlapping roles of DAT and SERT in regulating reward sensitivity, with implications for understanding individual vulnerability to substance use.

animal behavior and cognition↗

bioRxiv2023

FriendlyClearMap: An optimized toolkit for mouse brain mapping and analysis

Tissue clearing is currently revolutionizing neuroanatomy by enabling organ-level imaging with cellular resolution. However, currently available tools for data analysis require a significant time investment for training and adaptation to each laboratorys use case, which limits productivity. Here, we present FriendlyClearMap, an integrated toolset that makes ClearMap1 and ClearMap2s CellMap pipeline easier to use, extends its functions, and provides Docker Images from which it can be run with minimal time investment. We also provide detailed tutorials for each step of the pipeline. For more precise alignment, we add a landmark-based atlas registration to ClearMaps functions as well as include young mouse reference atlases for developmental studies. We provide alternative cell segmentation method besides ClearMaps threshold-based approach: Ilastiks Pixel Classification, importing segmentations from commercial image analysis packages and even manual annotations. Finally, we integrate BrainRender, a recently released visualization tool for advanced 3D visualization of the annotated cells. As a proof-of-principle, we use FriendlyClearMap to quantify the distribution of the three main GABAergic interneuron subclasses (Parvalbumin+, Somatostatin+, and VIP+) in the mouse fore- and midbrain. For PV+ neurons, we provide an additional dataset with adolescent vs. adult PV+ neuron density, showcasing the use for developmental studies. When combined with the analysis pipeline outlined above, our toolkit improves on the state-of-the-art packages by extending their function and making them easier to deploy at scale.

neuroscience↗