Finkelstein, J. | Search bioRxiv

bioRxiv2025

Chronic dietary ingestion of Bacillus thuringiensis spores promotes intestinal inflammation and aging in non-target adult Drosophila

Bacillus thuringiensis (Bt), a spore-forming Gram-positive bacterium, is the leading microbial insecticide used in both organic and conventional agriculture to fight lepidopteran larvae. Bt insecticides, which consist of a mix of Bt spores and crystals of entomopathogenic toxins (Cry toxins), kill target pest larvae rapidly after ingestion by destroying their intestinal epithelium. The potential adverse effects of chronic consumption of Bt spores by non-target organisms have not been thoroughly investigated. In this study, using adult Drosophila melanogaster, a non-target dipteran organism of Bt insecticides, we show that chronic ingestion of agricultural doses of spores in the diet reduces lifespan. Our results demonstrate that Bt spore ingestion affects gut morphology, promotes dysplasia, alters septate junctions and enhances epithelial permeability. In addition, we observed increased levels of inflammatory signaling pathways and reactive oxygen species. Taken together, our results indicate that chronic consumption of Bt spores promotes inflammation and oxidative stress, leading to premature aging of the gut and early lethality in Drosophila. Extended to non-target insects, which account for 85% of animal biodiversity, our study suggests that highly persistent Bt spores may have unintended long-term effects on the environment.

physiology↗

bioRxiv2018

Specialized and spatially organized coding of sensory, motor, and cognitive variables in midbrain dopamine neurons

There is increased appreciation that dopamine (DA) neurons in the midbrain respond not only to reward 1,2 and reward-predicting cues 1,3,4, but also to other variables such as distance to reward 5, movements 6-11 and behavioral choices 12-15. Based on these findings, a major open question is how the responses to these diverse variables are organized across the population of DA neurons. In other words, do individual DA neurons multiplex multiple variables, or are subsets of neurons specialized in encoding specific behavioral variables? The reason that this fundamental question has been difficult to resolve is that recordings from large populations of individual DA neurons have not been performed in a behavioral task with sufficient complexity to examine these diverse variables simultaneously. To address this gap, we used 2-photon calcium imaging through an implanted lens to record activity of >300 midbrain DA neurons in the VTA during a complex decision-making task. As mice navigated in a virtual reality (VR) environment, DA neurons encoded an array of sensory, motor, and cognitive variables. These responses were functionally clustered, such that subpopulations of neurons transmitted information about a subset of behavioral variables, in addition to encoding reward. These functional clusters were spatially organized, such that neighboring neurons were more likely to be part of the same cluster. Taken together with the topography between DA neurons and their projections, this specialization and anatomical organization may aid downstream circuits in correctly interpreting the wide range of signals transmitted by DA neurons.

neuroscience↗