Biology subjects

Weimar, H. V.

Publications and source records attributed to Weimar, H. V..

3 recordsLinked to original sources

bioRxiv2026

Cone photoreceptor ablation in microglia-deficient larval zebrafish retina elicits a regenerative response alongside a compensatory immune cell response

Emerging evidence implicates retinal microglia and inflammation as important components impacting the outcome of retinal regeneration, which is spontaneously achieved in zebrafish retina following acute damage but is limited or blocked in mammals. In this paper, we describe the regenerative response in the larval zebrafish retina following ablation of cone photoreceptors. To investigate the role of microglia in the regenerative response, we used both irf8st95 heterozygote (microglia-sufficient) and irf8st95 homozygous mutant (microglia-deficient) zebrafish. We compared multiple aspects of the regenerative response in irf8+/- and irf8-/- larval retinas, including entry of the Muller glia (MG) into the cell cycle, the amplification of MG-derived progenitor cell (MGPC) proliferation, inflammatory and glial reactivity-associated gene expression, and the regeneration of cones. We found only modest impacts to early and late stages of MGPC proliferation and to inflammatory gene expression in irf8 mutants, with no obvious impacts to the regeneration of cones. Notably, we detected a population of immune cells in irf8 mutants that emerged following cone ablation, which expanded in number then were reduced over time, following a trajectory similar to microglia-sufficient siblings but at markedly reduced abundance. The immune cells detected in irf8 mutants included a subset with L-plastin/4C4 antibody staining patterns different than those in microglia-sufficient siblings, suggesting distinct origins and/or phenotype compared to resident microglia in controls. Though strong conclusions about the role of microglia were limited due to the presence of such immune cell populations in irf8 mutants, our results are consistent with several reports that indicate a role for microglia and inflammation in regulating MGPC proliferation in the regenerating retina. Collectively considered with other reports, our results further indicate that compensatory responses, which may include different immune cells and/or signaling from other retinal cell types such as the Muller glia, are elicited in microglia-deficient retinas upon neuronal damage.

developmental biology↗

bioRxiv2024

Maternal cannabis use alters excitatory inputs to corticostriatal efferent neurons in rat offspring

With the recent surge in cannabis legalization across North America, there is legitimate concern that rates of cannabis use during pregnancy will dramatically increase in the coming years. However, the long-term impacts of prenatal cannabis exposure (PCE) on the brain and behavior remain poorly understood. Using a model of passive cannabis vapor exposure, we have previously shown that PCE impairs behavioral flexibility in an attentional set-shifting task in adult offspring, which is orchestrated in part by excitatory inputs from the medial prefrontal cortex (mPFC) to the nucleus accumbens (NAc). Given the fundamental role of these corticostriatal inputs in coordinating flexible reward-seeking strategies, we used a combination of retrograde tracing and ex vivo electrophysiology to test the hypothesis that maternal cannabis use alters the synaptic and intrinsic membrane properties of corticostriatal efferent neurons in exposed male and female rat offspring. Specifically, pregnant rat dams were trained to self-administer vaporized cannabis (69.7% THC; 150 mg/ml) twice daily throughout mating and gestation and offspring were subsequently injected with fluorescent retrobeads into the NAc core prior to conducting whole-cell ex vivo recordings of spontaneous excitatory and inhibitory post-synaptic currents (EPSC and IPSC, respectively) in retrolabeled mPFC neurons in adulthood. Our results indicate that PCE increases the frequency of spontaneous glutamatergic events (EPSCs) in NAc-projecting mPFC neurons in a sex-specific manner, which drives changes in excitatory to inhibitory (EPSC/IPSC) ratio, particularly in females. Furthermore, the amplitude of phasic glutamatergic events was reduced in cannabis-exposed offspring of both sexes, suggesting changes in postsynaptic receptor function. Altogether, these data demonstrate that PCE shifts the balance of excitatory/inhibitory inputs onto NAc-projecting mPFC neurons with limited effects on membrane conductance in females, resulting in reduced sex differences following maternal cannabis self-administration. These results provide putative neurophysiological mechanisms mediating previously observed behavioral changes, and future studies will need to test if these cannabis-induced changes are causal to long-term deficits in behavioral flexibility that have been previously documented in exposed offspring.

neuroscience↗

bioRxiv2020

Maternal cannabis vapor exposure causes long-term alterations in emotional reactivity, social behavior, and behavioral flexibility in offspring.

The use of cannabis during pregnancy is a growing public health concern. As more states implement legislation permitting recreational cannabis use, there is an urgent need to better understand its impact on fetal neurodevelopment and its long-term effects in exposed offspring. Studies examining effects of prenatal cannabis exposure typically employ injections of synthetic cannabinoids or isolated cannabis constituents that may not accurately model cannabis use in human populations. To address this limitation, we have developed a novel e-cigarette technology-based system to deliver vaporized cannabis extracts to pregnant Long Evans rats. We used this model to determine effects of prenatal cannabis exposure on emotional, social, and cognitive endpoints of male and female offspring during early development and into adulthood. Dams were exposed to cannabis vapor (CANTHC: 400 mg/ml), vehicle vapor (VEH), or no vapor (AIR) twice daily during mating and gestation. Offspring exposed to CANTHC and VEH showed reduced weight gain relative to AIR offspring prior to weaning. CANTHC offspring made more isolation-induced ultrasonic vocalizations (USVs) on postnatal day 6 (P6) relative to VEH-exposed offspring, which is indicative of increased emotional reactivity. Male CANTHC offspring engaged in fewer social investigation behaviors than VEH-exposed male offspring during a social play test on P26. In adulthood, CANTHC-exposed offspring spent less time exploring the open arms of the elevated plus maze and exhibited dose-dependent deficits in behavioral flexibility in an attentional set-shifting task relative to AIR controls. These data collectively indicate that prenatal cannabis exposure causes enduring effects on the behavioral profile of offspring.

neuroscience↗