Buursma, J. | bioRxiv Science

bioRxiv2025

Cell Type-Specific Changes in Dendritic Spines Across Adolescence Within Mouse Medial Prefrontal Cortex

Across species, cognitive capacities that rely on the frontal cortex do not fully mature until adulthood. Adolescent circuit refinement, including structural remodeling of dendritic spines, is believed to underlie this protracted maturation. Understanding cell type-dependent patterns of structural maturation would provide important insight into frontal cortex development. Here, we leveraged retrograde adeno-associated viruses to quantify dendritic spines on pyramidal tract (PT) vs. intratelencephalic (IT) neuronal populations in parallel within the mouse medial prefrontal cortex (mPFC) across adolescence. IT-type neurons showed opposing changes in mushroom and thin spines that were: 1) consistent with increasing synaptic maturity and 2) largely absent in PT-type neurons. We next probed the function of brain-resident immune cells, microglia, by transiently ablating them within the mPFC at mid-adolescence. This led to cell type-dependent changes in dendritic spines in late adolescence, with thin spine proportion increasing on both cell types but total spine density increasing on IT-type neurons only. Meanwhile, there was no effect on performance in an mPFC-dependent task of cognitive flexibility at either late adolescent or adult time points following microglia ablation. These findings provide evidence that mPFC IT-type neurons undergo greater spine remodeling during adolescence compared to PT-type neurons and implicate microglia as potential mediators.

neuroscience↗

bioRxiv2025

Influence of solvent, sex, and age on pharmacokinetic and acute behavioral effects of vaporized cannabis extract in mice

The legalization of cannabis in several states across the US has increased the need to better understand its effects on the body, brain, and behavior, particularly in different populations. Rodent models are particularly valuable in this respect because they provide precise control over external variables. Previous rodent studies have found age and sex differences in response to injected {Delta}9-tetrahydrocannabinol (THC), the major psychoactive component of cannabis. However, this route of administration does not mimic the most common way humans consume cannabis, i.e. through inhalation. Here, we sought to address this gap by investigating age and sex differences in pharmacokinetics and the acute behavioral effects of vaporized cannabis extract in mice. Adolescent (postnatal day [P] 35-50) and adult ([≥] P70) mice of both sexes received noncontingent exposure to 0 mg/ml, 150 mg/ml, or 300 mg/ml vaporized cannabis extract diluted in either 80% propylene glycol/20% vegetable glycerol (PG/VG) or 100% polyethylene glycol 400 (PEG). Immediately after exposure, body temperature, hot plate withdrawal latency, and locomotion were assessed. Blood was collected at 0, 30, and 60 min after vapor exposure, and plasma THC and its metabolites were analyzed. Measured THC levels were higher in both the plasma of vapor-exposed mice and the cannabis extract solutions themselves when PEG was the solvent compared to PG/VG. Vaporized cannabis (dissolved in PEG) at the highest dose tested induced hypothermic, antinociceptive, and locomotor-suppressing effects in all groups of mice. We found a dose-dependent age difference in locomotion, indicating that adolescents were less sensitive to the locomotor-suppressing effects of vaporized cannabis, which may be related to the plasma THC levels achieved. Although we found no significant sex differences in the acute behavioral effects of vaporized cannabis, there were significant sex differences in plasma THC metabolites indicating that female mice may metabolize vaporized cannabis more slowly than male mice. Taken together, the current findings add to a growing number of studies implementing vaporized cannabinoid delivery approaches by revealing PEG as the superior solvent for studies involving cannabis extract.

animal behavior and cognition↗