Biology subjects

Gregg, C.

Publications and source records attributed to Gregg, C..

9 recordsLinked to original sources

bioRxiv2026

Immersive display systems for simulating natural vision

Vision is traditionally studied using simplified stimuli presented briefly near the center of a flat display while subjects maintain visual fixation. This paradigm contrasts sharply with real-world vision, which is immersive, dynamic and strongly entrained to self-initiated actions. Traditional approaches have allowed researchers to systematically study the neural encoding of visual features and the influence of cognitive operations such as attention. However, other methods are needed to study more holistic and first-person perspectives on vision, such as those related to physical space, continuous time, and self-movement. To enable the study of these and other aspects of real-world vision, we developed hemispherical ("dome") display systems for macaque visual neuroscience. For functional MRI experiments, a compact rear-projection dome display fits within the bore of a clinical MRI scanner. For electrophysiological recordings, a larger front-projection dome display is illuminated from above using a spherical mirror. Both setups enable complete and dynamic stimulation of approximately 180{degrees} of the subjects field of view, thus facilitating studies requiring visual immersion. To ensure accurate angular geometry across the hemispherical display, we present unified rendering and calibration software that supports natural fisheye videos, conventional visual stimuli, and virtual 3D environments. The calibration procedure automatically compensates for projector, mirror, and dome distortions through geometric pre-warping, ensuring correct visual-angle representation across the display. Pilot fMRI experiments demonstrate robust activation of peripheral visual cortex during both conventional pattern stimulation and naturalistic self-movement. Together, these dome systems provide a flexible platform for investigating aspects of vision that are difficult to study with conventional displays, including peripheral processing, visual immersion, optic flow, self-motion, and holistic scene perception.

neuroscience↗

bioRxiv2026

Lightweight Adaptive and Recoverable Implants (LARI) for Chronic Single and Dual Neuropixels 2.0 Recordings for Naturalistic Behaviors in Feature-Rich Environments

Understanding the neural mechanisms underlying naturalistic decision-making requires chronic, high-quality neural recordings from distributed brain regions in freely behaving animals. However, existing silicon probe implants for mice are limited by weight, fragility, lack of independent probe adjustment, and poor suitability for long-term recordings in complex environments. Here we introduce LARI-1.0 (Lightweight Adjustable and Reusable Implant) and LARI-mini, two Neuropixels 2.0 implant systems designed for stable, recoverable, and independently adjustable single- and dual-probe recordings in mice. LARI-1.0 enables independent vertical and lateral positioning of two probes, while LARI-mini provides a lighter single-probe alternative, reducing implant mass by ~20%. Fully assembled weights of ~2.3 g (LARI-1.0) and ~1.5 g (LARI-mini) remain within 10% and 7.5% of adult male mouse body weight, respectively. We validated implant performance in a custom feature-rich naturalistic foraging environment that elicited full-body movements, rapid elevation changes, and ethological foraging behaviors across fed, fasted, and high-fat diet states. Both implants exhibited excellent mechanical stability, minimal motion-related artifacts, and probe drift comparable to previous studies. High-quality single-unit activity with stable waveform features, 5-6x signal-to-noise ratios, and no systematic loss of well-isolated units was maintained for up to 180 days. These results demonstrate that LARI-1.0 and LARI-mini provide lightweight, durable, and customizable implant solutions enabling long-term, high-fidelity neural recordings during naturalistic behavior.

neuroscience↗

bioRxiv2024

Conserved Noncoding Cis-Elements Associated with Hibernation Modulate Metabolic and Behavioral Adaptations in Mice

Our study elucidates functional roles for conserved cis-elements associated with the evolution of mammalian hibernation. Genomic analyses found topologically associated domains (TADs) that disproportionately accumulated convergent genomic changes in hibernators, including the TAD for the Fat Mass & Obesity (Fto) locus. Some hibernation-linked cis-elements in this TAD form regulatory contacts with multiple neighboring genes. Knockout mice for these cis-elements exhibit Fto, Irx3, and Irx5 gene expression changes, impacting hundreds of genes downstream. Profiles of pre-torpor, torpor, and post-torpor phenotypes found distinct roles for each cis-element in metabolic control, while a high caloric diet uncovered different obesogenic effects. One cis-element promoting a lean phenotype influences foraging behaviors throughout life, affecting specific behavioral sequences. Thus, convergent evolution in hibernators pinpoints functional genetic mechanisms of mammalian metabolic control. One-sentence summaryDeletions of conserved cis-elements tied to hibernator evolution causes diverse metabolic traits in mice.

genomics↗

bioRxiv2024

Genomic Convergence in Hibernating Mammals Elucidates the Genetics of Metabolic Regulation in the Hypothalamus

Elucidating the genetic basis of mammalian metabolism could help define mechanisms central to health and disease. Here, we define conserved cis-regulatory elements (CREs) and programs for mammalian metabolic control. We delineate gene expression and chromatin responses in the mouse hypothalamus for 7 steps of the Fed-to-Fasted-to-Refed (FFR) response process. Comparative genomics of hibernating versus non-hibernating lineages then illuminates cis-elements showing convergent changes in hibernators. Hibernators accumulated loss-of-function effects for specific CREs regulating hypothalamic FFR responses. Multi-omics approaches pinpoint key CREs, genes, regulatory programs, and cell types in the divergence of hibernating and homeothermic lineages. The refeeding period after extended fasting is revealed as one critical period of chromatin remodeling with convergent genomic changes. This genetic framework is a step toward harnessing hibernator adaptations in medicine. One sentence summaryConvergent signals define cis-regulatory mechanisms behind food scarcity responses and hibernator-homeotherm divergence.

genomics↗

bioRxiv2022

Arc Regulates a "Second-Guessing" Cognitive Bias During Naturalistic Foraging

Foraging involves innate decision heuristics that are adapted for the wild but can cause economically suboptimal cognitive biases in some contexts. The mechanisms underlying cognitive biases are poorly understood but are likely genetic. Here, we investigate foraging in fasted mice using a naturalistic paradigm and uncover an innate "second-guessing" cognitive bias that involves repeatedly investigating an empty former food patch instead of consuming available food. Second-guessing prevents mice from maximizing feeding benefits in the task. Since learning and memory are involved, we tested roles for the synaptic plasticity gene, Arc, and found that Arc-/- mice show a specific lack of second-guessing. Arc-/- males reap benefits by increasing food consumption. Unsupervised machine learning decompositions of foraging show that Arc affects discrete, stereotyped foraging sequences that we call modules within a rich naturalistic behavioral landscape. Thus, our study reports a second- guessing cognitive bias, ethological roles for Arc in naturalistic foraging, and links between genetically determined foraging modules and cognitive bias in decision making.

neuroscience↗

bioRxiv2020

Dopa decarboxylase is a genetic hub of parental control over offspring behavior

Dopa decarboxylase (DDC) regulates the synthesis of monoaminergic neurotransmitters and is linked to psychiatric and metabolic disorders. Ddc exhibits complex genomic imprinting effects that have not been functionally studied. Here, we investigate different noncanonical imprinting effects at the cellular level with a focus on Ddc. Using allele-specific reporter mice, we found Ddc exhibits dominant expression of the maternal allele in subpopulations of cells in 14 of 52 brain regions, and dominant paternal or maternal allele expression in adrenal cell subpopulations. Maternal versus paternal Ddc allele null mutations differentially affect offspring social, foraging and exploratory behaviors. Machine learning analyses of naturalistic foraging in Ddc-/+ and +/- offspring uncovered finite behavioral sequences controlled by the maternal versus paternal Ddc alleles. Additionally, parental Ddc genotype is revealed to affect behavior independent of offspring genotype. Thus, Ddc is a hub of maternal and paternal influence on behavior that mediates diverse imprinting and parental effects. HIGHLIGHTSO_LIDopa decarboxylase (Ddc) allelic expression resolved at the cellular level C_LIO_LICells differentially express maternal versus paternal Ddc alleles C_LIO_LIMaternal and paternal Ddc alleles control distinct behavioral sequences C_LIO_LIParental Ddc genotype affects offspring independent of mutation transmission C_LI eTOCAllelic reporter mice and machine learning analyses reveal dopa decarboxylase is affected by diverse imprinting and parental effects that shape finite behavioral sequences in sons and daughters.

neuroscience↗

bioRxiv2020

Elephant genomes reveal insights into differences in disease defense mechanisms between species

Disease susceptibility and resistance comprise important factors in conservation, particularly in elephants. To determine genetic mechanisms underlying disease resistance and other unique elephant traits, we estimated 862 and 1,017 potential regulatory elements in Asian and African elephants, respectively. These elements are significantly enriched in both species with differentially expressed genes involved in immunity pathways, including tumor-necrosis factor which plays a role in the response to elephant endotheliotropic herpesvirus (EEHV). Population genomics analyses indicate that amplified TP53 retrogenes are maintained by purifying selection and may contribute to cancer resistance in elephants, including less malignancies in African vs. Asian elephants. Positive selection scans across elephant genomes revealed genes that may control iconic elephant traits such as tusk development, memory, and somatic maintenance. Our study supports the hypothesis that interspecies variation in gene regulation contributes to differential inflammatory responses leading to increased infectious disease and cancer susceptibility in Asian versus African elephants. Genomics can inform functional immunological studies which may improve both conservation for elephants and human therapies.

evolutionary biology↗

bioRxiv2020

Characterizing the portability of RecT-mediated oligonucleotide recombination

Bacterial genome editing methods are used to engineer strains for biotechnology and fundamental research. Homologous recombination (HR) is the most versatile method of genome editing, but traditional techniques using endogenous RecA-mediated pathways are inefficient and laborious. Phage encoded RecT proteins can improve HR over 1000-fold, but these proteins have limited portability between species. Using Escherichia coli, Lactococcus lactis, Mycobacterium smegmatis, Lactobacillus rhamnosus, and Caulobacter crescentus we investigated the hostlimited functionality of RecTs. We find that these proteins specifically recognize the 7 C-terminal amino acids of the bacterial single-stranded DNA-binding protein (SSB), and are portable between species only if compatibility with this host domain is maintained. Furthermore, in some species, we find that co-expressing otherwise incompatible RecTs with a paired bacterial SSB is sufficient to establish functionality. Finally, we demonstrate that high-efficiency HR surpasses the mutational capacity of more widely used error-prone methods for genome diversification, and can be used to identify exceptional phenotypes inaccessible through sequential nucleotide conversions.

synthetic biology↗

bioRxiv2018

Machine Learning Reveals Modules of Economic Behavior from Foraging Mice

Complex ethological behaviors could be constructed from modules that are discrete functional units of behavior with a genetic basis. Here, we test this idea for foraging, and develop a paradigm to dissect foraging patterns in mice. We uncover discrete behavioral modules linked to round trip excursions from the home. Machine learning reveals 59 modules across different genetic backgrounds and ages. Different modules develop at different ages and are linked to different aspects of economic behavior, including memory, reward, risk and effort responses. Crosses of distant mouse strains reveal that parental and genetic effects shape foraging differently, and parental effects grow stronger with age. Specific behavioral modules, genes and pathways are found to be sensitive to parental effects. One candidate gene, Magel2, is linked to Prader-Willi Syndrome and shaped the expression of discrete modules in an age-dependent manner. Our results reveal building blocks for normal and abnormal economic behavior patterns.\n\nHIGHLIGHTSO_LIIdentification of 59 economic behavior modules underlying foraging\nC_LIO_LIDiscrete modules are linked to memory, reward, risk and effort responses\nC_LIO_LIGenetic and parental effects shape foraging by changing module expression\nC_LIO_LIMagel2, a Prader-Willi Syndrome gene, affects specific modules at specific ages\nC_LI

neuroscience↗