Biology subjects

Davis, G. O.

Publications and source records attributed to Davis, G. O..

4 recordsLinked to original sources

bioRxiv2026

Multidimensional control of ingestive behavior by lateral hypothalamic neurotensin neurons

Consumption of food and water is regulated by interactions between neural circuits that govern motivational drive states, arousal, motor activity, and reward signaling, among other factors. Neurons in the lateral hypothalamus that express the neuropeptide neurotensin (LH-Nts neurons) are known to influence many of these elements, but their precise role in regulating specific aspects of ingestive behavior remains unclear. Utilizing a tightly controlled head-fixed task, we find that LH-Nts neurons strongly encode the rate of licking for water and sweet solutions, with weaker modulation of activity by solution identity and restriction state. Silencing LH-Nts neurons reduces water intake but has little direct effect on hunger or satiety. Instead, we find that these neurons impact multiple underlying behavioral components necessary for food consumption, including arousal and engagement with a novel food source, and also influence thermoregulation and metabolism. Together, these data establish tonic activity of LH-Nts neurons as a critical signal supporting exploration and volitional movement, while also delineating a role for these neurons in driving active consumption, particularly of water. Furthermore, quantitative projection mapping revealed widespread innervation of structures linked to thirst, arousal, reward, metabolism, and facial motor control, suggesting that these neurons play an important role coordinating neural circuits governing multiple different aspects of ingestion.

neuroscience↗

bioRxiv2026

Periaqueductal gray neurotensin neurons drive simultaneousthreat response and reinforcement

The periaqueductal gray (PAG) is a midbrain structure known to influence responses to both threat and reward. The PAG sends projections to the ventral tegmental area (VTA), a region critical for regulating motivated behavior via dopamine release. We previously identified a population of VTA-projecting PAG neurons that express the peptide neurotensin (Nts), a potent dopamine neuron activator. Here we find that PAG-Nts neurons co-release glutamate and Nts in the VTA to drive dopamine neuron activation. These neurons are activated by threats and threat-predictive cues and are inhibited by entry into a shelter and during reward consumption. Optogenetic stimulation elicits a robust threat response, including freezing and tail rattle, but remarkably can also drive intracranial self-stimulation. This operant reinforcement behavior is dopamine dependent while the threat response is not. Together, these results identify a dual-output circuit that engages the dopamine system, likely to increase the salience of environmental stimuli, while simultaneously driving specific threat response behaviors.

neuroscience↗

bioRxiv2021

Tuberin levels during cellular differentiation in brain development

Tuberin is a member of a large protein complex, Tuberous Sclerosis Complex, and acts as a sensor for nutrient status regulating protein synthesis and cell cycle progression. Mutations in the Tuberin gene, TSC2, lead to the formation of tumors and developmental defects in many organ systems, including the central nervous system. Tuberin is expressed in the brain throughout development and levels of Tuberin have been found to decrease during neuronal differentiation in cell lines in vitro. Our current work investigates the levels of Tuberin at two stages of embryonic development in vivo, and we study the mRNA and protein levels during a time course using immortalized cell lines in vitro. Our results show that Tuberin levels remain stable in the olfactory bulb but decrease in the Purkinje cell layer during embryonic mouse brain development. We show here that Tuberin levels are higher when cells are cultured as neurospheres, and knockdown of Tuberin results in a reduction in the number of neurospheres. These data provide support for the hypothesis that Tuberin is an important regulator of stemness and the reduction of Tuberin levels might support functional differentiation in the central nervous system. Understanding how Tuberin expression is regulated throughout neural development is essential to fully comprehend the role of this protein in several developmental and neural pathologies. HIGHLIGHTSO_LITuberin protein levels are decreased in the Purkinje cell layer in later stages of embryonic development. C_LIO_LITuberin protein and mRNA levels decrease as cells undergo neuronal differentiation. C_LIO_LIDownregulation of Tuberin impairs neurosphere formation. C_LIO_LITuberin is implicated in the maintenance of stemness in the developing brain. C_LI

developmental biology↗

bioRxiv2018

Interpreting coronary artery disease risk through gene-environment interactions in gene regulation

GWAS and eQTL studies identified thousands of genetic variants associated with complex traits and gene expression. Despite the important role of environmental exposures in complex traits, only a limited number of environmental factors are measured in these studies. Measuring molecular phenotypes in tightly controlled cellular environments provides a more tractable setting to study gene-environment interactions in the absence of other confounding variables.\n\nWe performed RNA-seq and ATAC-seq in endothelial cells exposed to retinoic acid, dexamethasone, caffeine, and selenium to model genetic and environmental effects on gene regulation in the vascular endothelium, a common site of pathology in cardiovascular disease. We found that genes near regions of differentially accessible chromatin were more likely to be differentially expressed (OR = [3.41, 6.52], p < 10-16). Furthermore, we confirmed that environment-specific changes in transcription factor binding are a key mechanism for cellular response to environmental stimuli. SNPs in these transcription response factor footprints for dexamethasone, caffeine, and retinoic acid were enriched in GTEx eQTLs from artery tissues indicating that these environmental conditions are latently present in GTEx samples. Additionally, SNPs in footprints for response factors in caffeine are enriched in colocalized eQTLs for coronary artery disease (CAD), suggesting a role for caffeine in CAD risk. Interestingly, each treatment may amplify or buffer genetic risk for CAD, depending on the particular SNP considered.

genomics↗