Biology subjects

Harper, R. M.

Publications and source records attributed to Harper, R. M..

5 recordsLinked to original sources

bioRxiv2026

Dopamine serves as an independent gain regulator to shape striatal control of movement

Dopamine (DA) drives locomotion by modulating striatal activity in the dorsolateral striatum (DLS). How DA regulates motor function on subsecond timescales remains poorly understood. To address this question, we performed spectrally resolved triple-color fiber photometry, allowing us to simultaneously monitor DA, glutamatergic inputs, and pathway-specific spiny projection neuron (SPN) activity in freely moving mice during spontaneous behaviors as measured by unsupervised behavior quantifications. We showed that DA dynamics were temporally distinct from spontaneous locomotor kinematics or behavioral states. Instead, peri-event DA levels predicted SPN input-output (I/O) efficacy, defined as SPN activity relative to glutamatergic input, with opposite relationships across pathways: higher DA predicted enhanced efficacy in direct-pathway SPNs but reduced efficacy in indirect-pathway SPNs. Paired with unsupervised behavior quantification, elevating extracellular DA with methylphenidate, a DA re-uptake inhibitor, shifted direct-pathway SPNs toward higher I/O gain and indirect-pathway SPNs toward lower neuronal activity outputs, while biasing behavior toward selected mobile and turning states. Reserpine administration, which mediates DA vesicular depletion, resulted in the opposite efficacy shifts and increased occupancy of immobile states. Together, these findings support that DA does not simply encode spontaneous movement, but acts as a pathway-specific gain controller that dynamically tunes the transformation of glutamatergic input into SPN output to bias locomotor-state transitions in vivo.

neuroscience↗

bioRxiv2024

Sex-specific chemosensory gene expression in the whitelined sphinx moth (Lepidoptera: Hyles lineata) suggests a role for odorant-binding proteins in host plant choice

The whitelined sphinx moth, Hyles lineata, is a generalist during both the larval and adult stages with a broad geographic range extending across North and Central America. Within the genus Hyles there have been multiple transitions to a narrower host plant range, making Hyles an ideal group to study the evolution and mechanisms of host plant selection. We characterize sex- and appendage-specific chemosensory gene expression in H. lineata, the oldest extant member of the genus. We also describe female-specific gene expression in appendages used to sense plant surfaces as a means of identifying candidate genes involved in host plant choice. Sensilla on these appendages house sensory neurons and support cells that express chemosensory genes, receptors, and small proteins that bind, shuttle, and transport small molecules to allow detection of odorants and other small molecules. We considered genes detected more frequently in the female leg and ovipositor samples to be candidate oviposition-relevant genes. Most chemosensory genes of interest were detected in both sexes, while several odorant receptors were only detected in females. We identified 18 putative chemosensory genes that were specific to female legs, ovipositors, or both body parts. However, most of these genes did not reach statistical criteria to be considered differentially expressed. Instead, a set of OBPs show statistically significant female-biased expression in legs and ovipositors. These genes may serve as candidates for future study of the evolution and mechanisms of oviposition behavior in this species and its relatives. SummaryThe sphinx moth genus Hyles contains both generalist and specialized feeders, making it an ideal system to study the evolution of host plant breadth. The whitelined sphinx moth (Hyles lineata) is a generalist feeder at both adult and larval stages and is the oldest lineage of the genus. In this analysis of sex-specific gene expression, Godfrey and colleagues identify several odorant binding proteins as being more frequently detected in female appendages used to assess host plants. These genes could play a role in host plant selection and can be targets for future mechanistic studies on this species.

evolutionary biology↗

bioRxiv2023

Brain Connectivity Correlates of Breathing and Cardiac Irregularities in SUDEP: A Resting-State fMRI Study

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of premature mortality among people with epilepsy. Evidence from witnessed and monitored SUDEP cases indicate seizure-induced cardiovascular and respiratory failures; yet, the underlying mechanisms remain obscure. SUDEP occurs often during the night and early morning hours, suggesting that sleep or circadian rhythm-induced changes in physiology contribute to the fatal event. Resting-state fMRI studies have found altered functional connectivity between brain structures involved in cardiorespiratory regulation in later SUDEP cases and in individuals at high-risk of SUDEP. However, those connectivity findings have not been related to changes in cardiovascular or respiratory patterns. Here, we compared fMRI patterns of brain connectivity associated with regular and irregular cardiorespiratory rhythms in SUDEP cases with those of living epilepsy patients of varying SUDEP risk, and healthy controls. We analysed resting-state fMRI data from 98 patients with epilepsy (9 who subsequently succumbed to SUDEP, 43 categorized as low SUDEP risk (no tonic-clonic seizures (TCS) in the year preceding the fMRI scan), and 46 as high SUDEP risk (>3 TCS in the year preceding the scan)) and 25 healthy controls. The global signal amplitude (GSA), defined as the moving standard deviation of the fMRI global signal, was used to identify periods with regular ( low state) and irregular ( high state) cardiorespiratory rhythms. Correlation maps were derived from seeds in twelve regions with a key role in autonomic or respiratory regulation, for the low and high states. Following principal component analysis, component weights were compared between the groups. We found widespread alterations in connectivity of precuneus/posterior cingulate cortex in epilepsy compared to controls, in the low state (regular cardiorespiratory activity). In the low state, and to a lesser degree in the high state, reduced anterior insula connectivity (mainly with anterior and posterior cingulate cortex) in epilepsy appeared, relative to healthy controls. For SUDEP cases, the insula connectivity differences were inversely related to the interval between the fMRI scan and death. The findings suggest that anterior insula connectivity measures may provide a biomarker of SUDEP risk. The neural correlates of autonomic brain structures associated with different cardiorespiratory rhythms may shed light on the mechanisms underlying terminal apnea observed in SUDEP.

neuroscience↗

bioRxiv2023

Intermittent Hypoxia in Neonatal Rodents Affects Facial Bone Growth

Preterm human infants often show periodic breathing (PB) or apnea of prematurity (AOP), breathing patterns which are accompanied by intermittent hypoxia (IH). We examined cause-effect relationships between transient IH and reduced facial bone growth using a rat model. Neonatal pups from 14 timed pregnant Sprague-Dawley rats were randomly assigned to an IH condition, with oxygen altering between 10% and 21% every 4 min for 1 h immediately after birth, or to a litter-matched control group. The IH pups were compared with their age- and sex-matched control groups in body weight (WT), size of facial bones and nor-epinephrine (NE) levels in blood at 3, 4, and 5-weeks. Markedly increased activity of osteoclasts in sub-condylar regions of 3-week-old IH-treated animals appeared, as well as increased numbers of sympathetic nerve endings in the same region of tissue sections. Male IH-pups showed significantly higher levels of NE levels in sera at 3, 4 as well as 5-week-old time points. NE levels in 4- and-5-weekold female pups did not differ significantly. Intercondylar Width, Mandible Length and Intermolar Width measures consistently declined after IH insults in 3- and 4-week-old male as well as female animals. Three-week-old male IH-pups only showed a significantly reduced (p < 0.05) body weight compared to those of 3-week controls. However, female IH-pups were heavier than age-matched controls at all 3 time-points. Trabecular bone configuration, size of facial bones, and metabolism are disturbed after an IH challenge 1 h immediately after birth. The findings raise the possibility that IH, introduced by breathing patterns such as PB or AOP, induce significantly impaired bone development and metabolic changes in human newborns. The enhanced NE outflow from IH exposure may serve a major role in deficient bone growth, and may affect bone and other tissue influenced by that elevation.

developmental biology↗

bioRxiv2022

Sex differences in insular gyri responses to the cold pressor challenge

IntroductionSex differences in autonomic control may contribute to physiological sex differences in cardiovascular disease, thermoregulation, and the experience of pain. We previously showed sex differences in functional mapping of autonomic responses across the insula, a central autonomic control region. Anterior insula response patterns to sympathetic activation (Valsalva) and parasympathetic withdrawal (handgrip) differed between men and women. We here assessed sex differences in autonomic insula gyrus responses to a cold pressor challenge, which involves temperature and pain regulation. MethodsFunctional MRI (fMRI) involved a 1-minute right-foot cold pressor challenge in 22 women (age; mean{+/-}std: 50{+/-}4 yrs), and 39 men (45{+/-}3 yrs). Regions of interest (ROI) comprised left and right anterior short gyrus (ASG), middle short gyrus (MSG), posterior short gyrus (PSG), anterior long gyrus (ALG), and posterior long gyrus (PLG). Two-second time intervals of fMRI signal responses per ROI and concurrently recorded heart rate and blood oxygen saturation (SaO2) were tested for within- and between-group effects over time (repeated measures ANOVA P[≤]0.05). We tested sex differences in 1) each ROI; 2) lateralization effects; and 3) posterior-to-anterior gradients in responses. ResultsNo sex differences emerged in heart rate or SaO2. Women showed larger signal changes in several gyri than men after cold pressor onset and offset. Most consistently, women showed a greater right-over-left hemisphere dominance in cold pressor response compared to men in the MSG, PSG and ALG. Greater right-over-left hemisphere anterior-to-posterior dominance was more pronounced in men. ConclusionsThe findings confirm anterior and right-hemispheric dominance of insular responses during sympathetic activation that includes pain and cold. Although distinct transient male-female differences in fMRI responses appeared during the cold pressor, unlike the Valsalva and handgrip, no sex differences in ASG lateralization emerged, suggesting that the previously found sex differences may not solely relate to regulating blood pressure responses.

neuroscience↗