Biology subjects

Solis, O.

Publications and source records attributed to Solis, O..

4 recordsLinked to original sources

bioRxiv2026

Neurometabolic signatures of addiction vulnerability and heroin versus social seeking: a PET study in rats

Only a subset of heroin users develop addiction, characterized by binge-like heroin use and preference for heroin over other rewards, including social rewards. We recently established a rat model of these features. We trained rats to lever-press for social interaction and heroin (or saline, control) infusions and then tested heroin- and social-seeking and heroin-vs.-social choice. During 3-5 abstinence weeks, we used 2-deoxy-2-[{superscript 1}F]fluoro-D-glucose (FDG) PET imaging to assess regional brain metabolic activity at rest (homecage) and during heroin and social seeking. We assessed regional differences in FDG uptake using unbiased voxel-wise analysis and statistical parametric mapping, and correlated FDG uptake with principle-component-analysis-derived addiction severity score incorporating heroin intake, binge-like episodes, and heroin preference. Compared with saline-trained rats, heroin-trained rats showed overall higher FDG uptake across multiple brain regions at rest and during both reward-seeking tests. Comparison of heroin-vs.-social-seeking in heroin-trained rats showed higher uptake in claustrum/lateral striatum and auditory cortex during social seeking. Analysis of individual differences showed that addiction severity was primarily associated with metabolic alterations under resting conditions rather than during heroin- or social-seeking. At rest, higher addiction severity was associated with lower uptake in piriform cortex and higher uptake in ventral hippocampus, whereas during heroin-seeking, addiction severity was associated with lower uptake in post-subiculum and cerebellum. Addiction severity was not associated with differences in social seeking or FDG uptake during social seeking. These findings identify neurometabolic features of social and heroin seeking and heroin addiction vulnerability that can potentially serve as brain biomarkers and targets for neuromodulation. Significance StatementHeroin addiction develops in only a subset of users, yet the determinants of vulnerability versus resilience to addiction remain largely unknown. We combined a rat model capturing key features of heroin addiction, including binge-like heroin intake and preference for heroin over social interaction, with behavioral heroin- and social-seeking assays and longitudinal whole-brain metabolic imaging using FDG-PET. We identified distinct patterns of neurometabolic alterations associated with heroin self-administration and addiction severity at rest and in the context of heroin seeking. In contrast, heroin self-administration and addiction severity were not significantly associated with neurometabolic alterations during social seeking. These findings highlight brain-wide neurometabolic features of vulnerability to heroin addiction that can serve as brain biomarkers and targets for neuromodulation.

neuroscience↗

bioRxiv2025

Steady-State Visually Evoked Potentials as Readouts for Abnormal GSK3β Activity in Drosophila

Glycogen synthase kinase 3{beta} (GSK3{beta}) is important in neuronal development and maintenance, acting as a key regulator by controlling a broad range of cellular processes. The effects of its dysregulation range from impairments in axonal transport and energy metabolism to synapse formation and neuronal plasticity. However, how such cellular defects link to neuronal dysfunction is less well studied despite the links between GSK3{beta} and various neurological conditions, such as Alzheimers and Parkinsons diseases, mood disorders and autism. Here we used a steady-state visually evoked potential (SSVEP) assay with Drosophila to measure the effect of altering GSK3{beta} expression on neuronal function. We recorded SSVEPs from flies that expressed constitutively active or inactive (kinase-dead) variants of GSK3{beta} and showed that the visual responses of these flies differed from those of controls. This was indicated by increased response latency and reduced photoreceptor maximum response (Rmax). Importantly, multivariate pattern classification can distinguish between over- and inactive GSK3{beta} conditions. Taken together, we show that SSVEPs provide a powerful tool for future studies to link the molecular and cellular functions of GSK3{beta} with their effects on neuronal function. Furthermore, we introduce a monitoring protocol that ensures the quality of datasets to support future fly SSVEP experiments.

neuroscience↗

bioRxiv2022

Activation of the fear-responsive anterior hypothalamic area promotes avoidance and triggers compulsive grooming behavior in mice

The anterior hypothalamic area (AHA) is a key brain region for orchestrating defensive behaviors. Here, we first examined AHA activity patterns during fear conditioning using in vivo functional imaging. We observed that neuronal activity in the AHA increases during both foot shock delivery and foot-shock associated auditory cues. Moreover, we used a combination of optogenetics and behavioral assays to determine the functional connectivity between the ventromedial hypothalamus (VMH) and the AHA. We found that photoactivation of the VMH[->]AHA pathway is aversive and triggers compulsive grooming behavior. Furthermore, we observed spatial and temporal changes of grooming behavior during the periods following VMH[->]AHA photoactivation. Interestingly, whole brain metabolic mapping using positron emission tomography (PET) combined with optogenetic activation of the VMH[->]AHA pathway in anesthetized mice revealed the amygdala as a downstream area activated by the stimulation of this pathway. Together, our findings show that the AHA responds to threat and that such increases in activity are sufficient to trigger compulsive grooming behavior. Thus, our results may help to understand some neuropsychiatric disorders characterized by repetitive and compulsive behaviors.

neuroscience↗

bioRxiv2022

The SARS-CoV-2 spike protein binds and modulates estrogen receptors

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 (ACE2) at the cell surface, which constitutes the primary mechanism driving SARS-CoV-2 infection. Molecular interactions between the transduced S and endogenous proteins likely occur post-infection, but such interactions are not well understood. We used an unbiased primary screen to profile the binding of full-length S against >9,000 human proteins and found significant S-host protein interactions, including one between S and human estrogen receptor alpha (ER). After confirming this interaction in a secondary assay, we used bioinformatics, supercomputing, and experimental assays to identify a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 subunit and an S-ER binding mode. In cultured cells, S DNA transfection increased ER cytoplasmic accumulation, and S treatment induced ER-dependent biological effects and ACE2 expression. Noninvasive multimodal PET/CT imaging in SARS-CoV-2-infected hamsters using [18F]fluoroestradiol (FES) localized lung pathology with increased ER lung levels. Postmortem experiments in lung tissues from SARS-CoV-2-infected hamsters and humans confirmed an increase in cytoplasmic ER expression and its colocalization with S protein in alveolar macrophages. These findings describe the discovery and characterization of a novel S-ER interaction, imply a role for S as an NRC, and are poised to advance knowledge of SARS-CoV-2 biology, COVID-19 pathology, and mechanisms of sex differences in the pathology of infectious disease.

immunology↗