Biology subjects

Morris, A. R.

Publications and source records attributed to Morris, A. R..

5 recordsLinked to original sources

bioRxiv2025

Two classes of amine/glutamate multi-transmitter neurons innervate Drosophila internal male reproductive organs

The essential outcome of a successful mating is the transfer of genetic material from males to females in sexually reproducing animals from insects to mammals. In males, this culminates in ejaculation, a precisely timed sequence of organ contractions driven by the concerted activity of interneurons, sensory neurons, and motor neurons. Although central command circuits that trigger copulation have been mapped, the motor architecture and the chemical logic that couple specific neuronal subclasses to organ specific contractility, seminal fluid secretion, and sperm emission remain largely uncharted. This gap in knowledge limits our ability to explain how neural circuits adapt to varying contexts and how their failure contributes to infertility. Here we present an in-depth anatomical and functional analysis of the motor neurons that innervate the internal male reproductive tract of Drosophila melanogaster. We identify two classes of multi-transmitter motor neurons based on neurotransmitter usage, namely octopamine and glutamate neurons (OGNs) and serotonin and glutamate neurons (SGNs), each with a biased pattern of innervation: SGNs predominate in the accessory glands, OGNs in the ejaculatory duct, with equal contributions of each to the seminal vesicles. Both classes co-express vesicular transporters for glutamate (vGlut) and amines (vMAT), confirming their dual chemical identity. Their target organs differentially express receptors for glutamate, octopamine, and serotonin, suggesting combinatorial neuromodulation of contractility. Functional manipulations show that SGNs are essential for male fertility but OGNs are dispensable. Glutamatergic transmission from both classes is also dispensable for fertility. These findings provide the first high-resolution map linking multi-transmitter motor neurons to specific reproductive organs, reveal an unexpected division of labor between serotonergic and octopaminergic signaling pathways, and establish a framework for dissecting conserved neural principles that govern ejaculation and male fertility.

neuroscience↗

bioRxiv2023

Sleep Disruption in a Mouse Model of Chronic Traumatic Brain Injury

Chronic sleep/wake disturbances are strongly associated with traumatic brain injury (TBI) in patients and are being increasingly recognized. However, the underlying mechanisms are largely understudied and there is an urgent need for animal models of lifelong sleep/wake disturbances. The objective of this study was to develop a chronic TBI rodent model and investigate the lifelong chronic effect of TBI on sleep/wake behavior. We performed repetitive midline fluid percussion injury (rmFPI) in four months old mice and monitored their sleep/wake behavior using the non-invasive PiezoSleep system. The sleep/wake states were recorded before injury (baseline) and then monthly thereafter. We found that TBI mice displayed a significant decrease in sleep duration in both the light and dark phases, beginning at three months post-TBI and continuing throughout the study. Consistent with the sleep phenotype, these TBI mice showed circadian locomotor activity phenotypes and exhibited reduced anxiety-like behavior. TBI mice also gained less weight, and had less lean mass and total body water content, compared to sham controls. Furthermore, TBI mice showed extensive brain tissue loss and increased GFAP and IBA1 levels in the hypothalamus and the vicinity of the injury, indicative of chronic neuropathology. In summary, our study identified a critical time window of TBI pathology and associated circadian and sleep/wake phenotypes. Future studies should leverage this mouse model to investigate the molecular mechanisms underlying the chronic sleep/wake phenotypes following TBI early in life.

neuroscience↗

bioRxiv2022

Defining the age-dependent and tissue-specific circadian transcriptome in male mice

Cellular circadian clocks direct a daily transcriptional program that supports homeostasis and resilience. Emerging evidence supports age-associated changes in circadian functions. To define age-dependent changes at the systems level, we profiled the circadian transcriptome in the hypothalamus, lung, heart, kidney, skeletal muscle, and adrenal gland in 3 age groups. We found age-dependent and tissue-specific clock output changes. Aging reduced the number of rhythmically expressed genes (REGs), indicative of weakened circadian control. Many genes gained rhythmicity in old tissues, reflecting an adaptive response. REGs were enriched for the hallmarks of aging, adding a new dimension to our understanding of aging. Differential gene expression analysis found that there were temporally distinct clusters of genes in tissue-specific manner. Increased daily gene expression variability is a common feature of aged tissues. This novel analysis extends the landscape of the understanding of aging and highlights the impact of aging on circadian clock function and temporal changes in gene expression. HIGHLIGHTS- Rhythmically expressed genes (REGs) in Young, but not Old mice, are enriched for the aging hallmarks across all tissues. - The numbers of REGs decline across all tissues with age implicating the circadian clock in altered homeostasis. - Age- and tissue-specific differentially expressed genes (DEGs) cluster at specific times of the day. - Increase in gene expression variability over a day is a common feature of aging tissues.

genomics↗

bioRxiv2021

Machine learning approaches to identify sleep genes

Genetics impacts sleep, yet, the molecular mechanisms underlying sleep regulation remain elusive. We built machine learning (ML) models to predict genes based on their similarity to known sleep genes. Using a manually curated list of 109 labeled sleep genes, we trained a prediction model on thousands of published datasets, representing circadian, immune, sleep deprivation, and many other processes. Our predictions fit with prior knowledge of sleep regulation and also identify several key genes/pathways to pursue in follow-up studies. We tested one of our findings, the NF-{kappa}B pathway, and showed that its genetic alteration affects sleep duration in mice. Our study highlights the power of ML to integrate prior knowledge and genome-wide data to study genetic regulation of sleep and other complex behaviors.

genomics↗

bioRxiv2020

A streamlined, cost-effective, and specific method to deplete transcripts for RNA-seq

RNA-sequencing is a powerful and increasingly prevalent method to answer biological questions. Depletion of ribosomal RNA (rRNA), which accounts for 80% of total RNA, is an extremely important step to increase the power of RNA-seq. Selection for polyadenylated RNA is a commonly used approach that excludes rRNA, as well as, important non-polyadenylated RNAs, such as histones, circular RNAs, and many long noncoding RNAs. Commercial methods to deplete rRNA are cost-prohibitive and the gold standard method is no longer available as a standalone kit. Alternative non-commercial methods suffer from inconsistent depletion. Through careful characterization of all reaction parameters, we developed an optimized RNaseH-based depletion of human rRNA. Our method exhibited comparable or better rRNA depletion compared to commercial kits at a fraction of the cost and across a wide-range of input RNA amounts.

molecular biology↗