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Full-Text Articles in Medical Sciences

Sox11 Overexpression Restores Embryonic Pro-Growth Transcription In Mature Corticospinal Tract Neurons, Eliazbeth Batsel, Zimei Wang, Elizabeth Otten, Syed Roshan, Rabia Mohammad, Paula Pascual, Darby O'Shea, Jose Rosas, Pantelis Tsoulfas, Murray G. Blackmore Jan 2026

Sox11 Overexpression Restores Embryonic Pro-Growth Transcription In Mature Corticospinal Tract Neurons, Eliazbeth Batsel, Zimei Wang, Elizabeth Otten, Syed Roshan, Rabia Mohammad, Paula Pascual, Darby O'Shea, Jose Rosas, Pantelis Tsoulfas, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

Neurons in the central nervous system (CNS) display a high capacity for axon growth during early development but lose this ability at a pivotal differentiation stage marked by synaptic maturation, circuit integration, and a profound shift in gene transcription. Once mature, most CNS neurons fail to reverse this transcriptional switch after axon injury, fundamentally constraining their intrinsic capacity for axon regeneration. Here, we show with single-nucleus RNA sequencing that forced expression of the transcription factor Sox11 in mature corticospinal tract (CST) neurons produces large-scale and stable changes in gene expression that are highly enriched for growth-relevant processes, and which strongly …


Dopaminergic Regulation Of Aversive Motivation, Elaine M. Grafelman Dec 2025

Dopaminergic Regulation Of Aversive Motivation, Elaine M. Grafelman

Dissertations (1934 -)

We all experience adversity in our lives, and we must be able to effectively respond to these challenges in order to thrive. One way to respond to stressors is to change one’s behavior to cope with the stress. This can include escaping or avoiding the stressor, focusing effort to diminish the effect of the stressor, or other coping strategies such as drug use. In fact, stress is one of the principal triggers of relapse for those in the abstinence phase of a substance use disorder and it exacerbates a variety of other disorders. Therefore, it is critical to understand the …


Activation Of Pro-Regenerative Gene Programs In The Mature Central Nervous System, Elizabeth Carlisle Batsel Dec 2025

Activation Of Pro-Regenerative Gene Programs In The Mature Central Nervous System, Elizabeth Carlisle Batsel

Dissertations (1934 -)

Spinal cord injury (SCI) affects millions of people worldwide. Damage to the spinal cord disrupts the long-distance axon tracts of central nervous system (CNS) neurons. These axons fail to regenerate, leading to permanent dysfunction. Past work has shown that CNS neurons lose the capacity to elongate their axons as they mature. Conversely, after injury, embryonic and peripheral nervous system (PNS) neurons can elongate axons towards target cells, driven by the growth cone at the growing tip of the axon. Previous research has identified transcription factor (TF) families, such as the SoxC family, that contribute to embryonic and peripheral neurons’ high …


Reproducibility Of Fnirs Within Subject For Visual And Motor Tasks, Julie C. Wagner, Anthony Zinos, Scott A. Beardsley, Wei-Liang Chen, Lisa Conant, Marsha Malloy, Joseph Heffernan, Brendan Quirk, Robert W. Prost, Mohit Maheshwari, Jeffrey Sugar, Harry T. Whelan Nov 2025

Reproducibility Of Fnirs Within Subject For Visual And Motor Tasks, Julie C. Wagner, Anthony Zinos, Scott A. Beardsley, Wei-Liang Chen, Lisa Conant, Marsha Malloy, Joseph Heffernan, Brendan Quirk, Robert W. Prost, Mohit Maheshwari, Jeffrey Sugar, Harry T. Whelan

Biomedical Sciences Faculty Research and Publications

Functional Near Infrared Spectroscopy (fNIRS) is becoming a popular metric to noninvasively identify brain activity through assessing changes in oxygenated (HbO) and deoxygenated (HbR) hemoglobin concentration. Several aspects of fNIRS imaging are appealing for clinical applications but the reproducibility of fNIRS signals has yet to be determined over several sessions. To address this, four participants completed at least ten sessions on separate days where they performed Motor and Visual tasks while fNIRS signals were measured from 102 channels spanning the entire head. Reproducibility was quantified as the percentage of significant task related activity occurring across sessions at the channel and …


Signaling By Intracellular Β2-Adrenergic Receptors Regulates Ampa Receptor Trafficking And Synaptic Plasticity, Paul J. Gasser Aug 2025

Signaling By Intracellular Β2-Adrenergic Receptors Regulates Ampa Receptor Trafficking And Synaptic Plasticity, Paul J. Gasser

Biomedical Sciences Faculty Research and Publications

Signaling by norepinephrine (NE) via adrenergic receptors (ARs) mediates attention, yet the underlying molecular mechanisms are largely unknown. AMPA receptors (AMPARs) form a complex with β2ARs, Gs, adenylyl cyclase, and protein kinase A (PKA) to augment AMPAR phosphorylation and, thereby, surface expression. We show that signaling by intracellular β2ARs is required for these effects and two different forms of long-term potentiation (LTP) that depend on β2AR signaling and phosphorylation of the AMPAR GluA1 subunit on S845. Inhibition of two NE transporters, the organic cation transporter 3 (OCT3) and the plasma membrane monoamine transporter (PMAT), impairs phosphorylation of the AMPAR GluA1 …


Interactions Between Explicit And Implicit Memories During Sensorimotor Adaptation And After Concussion, Devon Lantagne Apr 2025

Interactions Between Explicit And Implicit Memories During Sensorimotor Adaptation And After Concussion, Devon Lantagne

Dissertations (1934 -)

Sensorimotor adaptation is a form of motor learning whereby a motor skill is adjusted in the face of a disturbance to return performance to desired performance. This process uses memories of previous experiences to guide future movements. While the temporal characteristics of adaptation have been well studied, the extent to which these memories are explicit, implicit, or a mixture of both is unclear. In this Dissertation, I conduct three studies to investigate the relative contributions of sensorimotor memories when adapting to stochastic spring-like loads applied to the hand. By implementing computational modeling and system identification techniques, I fit memory models …


Role For Astrocytes In Complex Cognition: An Evolutionary, Behavioral And Computational Perspective, Gregory Simandl Apr 2025

Role For Astrocytes In Complex Cognition: An Evolutionary, Behavioral And Computational Perspective, Gregory Simandl

Dissertations (1934 -)

The human brain has more computational power than modern supercomputers by utilizing only a few signaling systems, rendering it the most efficient computational device ever created. Evolution, though not prospective, has iteratively constructed neural networks of increasing complexity that have ultimately endowed humans with extraordinary cognitive abilities. Through an evolutionary lens, there is a clear correlation between organismal sophistication and network signaling complexity Astrocytes, a non-neuronal cell that makes up approximately half the cells in the human brain, show dramatic increases in morphological and signaling complexity in higher-order species. This co-evolution is likely not coincidental but rather represents the development …


Aversion-Induced Dopamine Reductions Predict Drug-Taking And Escape Behaviors, Elaine M. Grafelman, Bridgitte E. Côté, Lisa Vlach, Ella Geise, G. Nino Padula, Daniel S. Wheeler, Matthew C. Hearing, John R. Mantsch, Robert A. Wheeler Apr 2025

Aversion-Induced Dopamine Reductions Predict Drug-Taking And Escape Behaviors, Elaine M. Grafelman, Bridgitte E. Côté, Lisa Vlach, Ella Geise, G. Nino Padula, Daniel S. Wheeler, Matthew C. Hearing, John R. Mantsch, Robert A. Wheeler

Biomedical Sciences Faculty Research and Publications

Dopamine release in the nucleus accumbens core (NAcC) has long been associated with the promotion of motivated behavior. However, inhibited dopamine signaling can increase behavior in certain settings, such as during drug self-administration. While aversive environmental stimuli can reduce dopamine, it is unclear whether such stimuli reliably engage this mechanism in different contexts. Here we compared the physiological and behavioral responses to the same aversive stimulus in different designs to determine if there is uniformity in the manner that aversive stimuli are encoded and promote behavior. NAcC dopamine was measured using fiber photometry in male and female rats during cocaine …


Single-Nuclei Sequencing Reveals A Robust Corticospinal Response To Nearby Axotomy But Overall Insensitivity To Spinal Injury, Zimei Wang, Manojkumar Kumaran, Elizabeth Bastel, Sofia Testor-Cabrera, Zac Beine, Alicia Alvarez Ribelles, Pantelis Tsoulfas, Ishwariya Venkatesh, Murray G. Blackmore Feb 2025

Single-Nuclei Sequencing Reveals A Robust Corticospinal Response To Nearby Axotomy But Overall Insensitivity To Spinal Injury, Zimei Wang, Manojkumar Kumaran, Elizabeth Bastel, Sofia Testor-Cabrera, Zac Beine, Alicia Alvarez Ribelles, Pantelis Tsoulfas, Ishwariya Venkatesh, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

The ability of neurons to sense and respond to damage is crucial for maintaining homeostasis and facilitating nervous system repair. For some cell types, notably dorsal root ganglia and retinal ganglion cells, extensive profiling has uncovered a significant transcriptional response to axon injury, which influences survival and regenerative outcomes. In contrast, the injury responses of most supraspinal cell types, which display limited regeneration after spinal damage, remain mostly unknown. In this study, we used single-nuclei sequencing in adult male and female mice to profile the transcriptional responses of diverse supraspinal cell types to spinal injury. Surprisingly, thoracic spinal injury induced …


From Misinformation To Policy Solutions: Teaching Herd Immunity And Vaccine Hesitancy Through Real-World Case Studies Of Measles Outbreaks, Laurieann Klockow Jan 2025

From Misinformation To Policy Solutions: Teaching Herd Immunity And Vaccine Hesitancy Through Real-World Case Studies Of Measles Outbreaks, Laurieann Klockow

Biomedical Sciences Faculty Research and Publications

Vaccine hesitancy threatens herd immunity, contributing to the resurgence of measles outbreaks. This lesson engages upper-level biomedical science students in analyzing the complex interplay between vaccination rates, herd immunity and vaccine exemption policies through examination of the 2019 New York measles outbreak that threatened the United States’ measles elimination status. Students critically evaluate anti-vaccine misinformation, analyze epidemiological data and develop evidence-based policy recommendations to increase vaccination rates. The lesson combines team-based learning with authentic assessment through vaccine policy development, moving beyond knowledge acquisition and content to building scientific literacy and evidence-based reasoning skills essential for scientifically literate citizens and future …


Variation In Craniodental Pathologies Among Cercopithecoid Primates, Claire A. Kirchhoff, Siobhán B. Cooke, Jessica C. Gomez, D. Rex Mitchell, Tyler Stein, Claire E. Terhune Nov 2024

Variation In Craniodental Pathologies Among Cercopithecoid Primates, Claire A. Kirchhoff, Siobhán B. Cooke, Jessica C. Gomez, D. Rex Mitchell, Tyler Stein, Claire E. Terhune

Biomedical Sciences Faculty Research and Publications

Pathologies of the skull and teeth are well documented for many human populations, but there are fewer studies of other primates. We contrast lesion prevalence and patterning among cercopithecoid primates and map variation onto socioecological variables. We compare craniodental lesions in six species: Nasalis larvatus (n = 54), Colobus polykomos (n = 64), Cercopithecus mitis (n = 65), Macaca fascicularis (n = 109), Theropithecus gelada (n = 13), and Papio anubis (n = 76). One of us (C.A.K.) evaluated each adult skull for multiple lesion types using standard criteria. We also tested for a …


Eaat4-Dependent Effects On Glutamatergic Signaling In The Cerebellar Molecular Layer, Christopher Chen Apr 2024

Eaat4-Dependent Effects On Glutamatergic Signaling In The Cerebellar Molecular Layer, Christopher Chen

Dissertations (1934 -)

Glutamatergic signaling is fundamental to human behavior and its dysfunction is implicated in a wide range of neurological and neurodegenerative disorders. Excitatory amino-acid transporters (EAATs) – of which four primary subtypes (EAAT1, EAAT2, EAAT3, and EAAT4) exist in the human brain – are primary regulators of glutamate signaling. Endogenously-expressed at either low (EAAT4-low) or high (EAAT4-high) concentration in cerebellar Purkinje cells, EAAT4 has been shown to regulate Purkinje cell activity in the cerebellar molecular layer. However, differences in glutamatergic signaling at the circuit and single-synaptic levels in EAAT4-low and EAAT4-high regions are poorly understood. To characterize EAAT4-specific effects on excitatory …


Specialized Astrocytes Mediate Glutamatergic Gliotransmission In The Cns, Roberta De Ceglia, Ada Ledonne, David Gregory Litvin, Barbara Lykke Lind, Giovanni Carriero, Emanuele Claudio Latagliata, Erika Bindocci, Maria Amalia Di Castro, Iaroslav Savtchouk, Ilaria Vitali, Anurag Ranjak, Mauro Congiu, Tara Canonica, William Wisden, Kenneth Harris, Manuel Mameli, Nicola Mercuri, Ludovic Telley, Andrea Volterra Oct 2023

Specialized Astrocytes Mediate Glutamatergic Gliotransmission In The Cns, Roberta De Ceglia, Ada Ledonne, David Gregory Litvin, Barbara Lykke Lind, Giovanni Carriero, Emanuele Claudio Latagliata, Erika Bindocci, Maria Amalia Di Castro, Iaroslav Savtchouk, Ilaria Vitali, Anurag Ranjak, Mauro Congiu, Tara Canonica, William Wisden, Kenneth Harris, Manuel Mameli, Nicola Mercuri, Ludovic Telley, Andrea Volterra

Biomedical Sciences Faculty Research and Publications

Multimodal astrocyte–neuron communications govern brain circuitry assembly and function. For example, through rapid glutamate release, astrocytes can control excitability, plasticity and synchronous activity of synaptic networks, while also contributing to their dysregulation in neuropsychiatric conditions. For astrocytes to communicate through fast focal glutamate release, they should possess an apparatus for Ca2+-dependent exocytosis similar to neurons. However, the existence of this mechanism has been questioned owing to inconsistent data and a lack of direct supporting evidence. Here we revisited the astrocyte glutamate exocytosis hypothesis by considering the emerging molecular heterogeneity of astrocytes and using molecular, bioinformatic and imaging approaches, together with …


Somatostatin Regulates Central Clock Function And Circadian Responses To Light, Deborah A.M. Joye, Kayla E. Rohr, Kimberlee Suenkens, Alissa Wuorinen, Thomas Inda, Madeline Arzbecker, Emma Mueller, Alec Huber, Harshida Pancholi, Murray G. Blackmore, Vania Carmona-Alcocer, Jennifer A. Evans Apr 2023

Somatostatin Regulates Central Clock Function And Circadian Responses To Light, Deborah A.M. Joye, Kayla E. Rohr, Kimberlee Suenkens, Alissa Wuorinen, Thomas Inda, Madeline Arzbecker, Emma Mueller, Alec Huber, Harshida Pancholi, Murray G. Blackmore, Vania Carmona-Alcocer, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

Daily and annual changes in light are processed by central clock circuits that control the timing of behavior and physiology. The suprachiasmatic nucleus (SCN) in the anterior hypothalamus processes daily photic inputs and encodes changes in day length (i.e., photoperiod), but the SCN circuits that regulate circadian and photoperiodic responses to light remain unclear. Somatostatin (SST) expression in the hypothalamus is modulated by photoperiod, but the role of SST in SCN responses to light has not been examined. Our results indicate that SST signaling regulates daily rhythms in behavior and SCN function in a manner influenced by sex. First, we …


Developmental Patterning Of Peptide Transcription In The Central Circadian Clock In Both Sexes, Vania Carmona-Alcocer, Lindsey S. Brown, Aisha Anchan, Kayla E. Rohr, Jennifer A. Evans Jan 2023

Developmental Patterning Of Peptide Transcription In The Central Circadian Clock In Both Sexes, Vania Carmona-Alcocer, Lindsey S. Brown, Aisha Anchan, Kayla E. Rohr, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

Introduction: Neuropeptide signaling modulates the function of central clock neurons in the suprachiasmatic nucleus (SCN) during development and adulthood. Arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) are expressed early in SCN development, but the precise timing of transcriptional onset has been difficult to establish due to age-related changes in the rhythmic expression of each peptide.

Methods: To provide insight into spatial patterning of peptide transcription during SCN development, we used a transgenic approach to define the onset of Avp and Vip transcription. Avp-Cre or Vip-Cre males were crossed to Ai9+/+ females, producing offspring in which the fluorescent protein …


On The Origin And Evolution Of The Dual Oscillator Model Underlying The Photoperiodic Clockwork In The Suprachiasmatic Nucleus, Jennifer A. Evans, William J. Schwartz Jan 2023

On The Origin And Evolution Of The Dual Oscillator Model Underlying The Photoperiodic Clockwork In The Suprachiasmatic Nucleus, Jennifer A. Evans, William J. Schwartz

Biomedical Sciences Faculty Research and Publications

Decades have now passed since Colin Pittendrigh first proposed a model of a circadian clock composed of two coupled oscillators, individually responsive to the rising and setting sun, as a flexible solution to the challenge of behavioral and physiological adaptation to the changing seasons. The elegance and predictive power of this postulation has stimulated laboratories around the world in searches to identify and localize such hypothesized evening and morning oscillators, or sets of oscillators, in insects, rodents, and humans, with experimental designs and approaches keeping pace over the years with technological advances in biology and neuroscience. Here, we recount the …


Effects Of Ethanol On Glun1/Glun2a And Glun1/Glun2b Nmda Receptor-Ion Channel Gating Kinetics, Robert W. Peoples, Hong Ren Dec 2022

Effects Of Ethanol On Glun1/Glun2a And Glun1/Glun2b Nmda Receptor-Ion Channel Gating Kinetics, Robert W. Peoples, Hong Ren

Biomedical Sciences Faculty Research and Publications

Background

The N-methyl-D-aspartate receptor (NMDAR) is a major molecular target of alcohol action in the central nervous system, yet many aspects of alcohol's modulation of the activity of this ion channel remain unclear. We and others have shown that ethanol inhibition of NMDAR involves alterations in gating, especially a reduction in mean open time. However, a full description of ethanol's effects on NMDAR kinetics, including fitting them to a kinetic model, has not been reported.

Methods

To determine ethanol's effects on NMDAR kinetics, we used steady-state single-channel recording in outside-out patches from HEK-293 cells transfected with recombinant GluN1/GluN2A or …


Single Nuclei Analyses Reveal Transcriptional Profiles And Marker Genes For Diverse Supraspinal Populations, Zachary Beine, Zimei Wang, Pantelis Tsoulfas, Murray G. Blackmore Nov 2022

Single Nuclei Analyses Reveal Transcriptional Profiles And Marker Genes For Diverse Supraspinal Populations, Zachary Beine, Zimei Wang, Pantelis Tsoulfas, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

The mammalian brain contains numerous neurons distributed across forebrain, midbrain, and hindbrain that project axons to the lower spinal cord and work in concert to control movement and achieve homeostasis. Extensive work has mapped the anatomic location of supraspinal cell types and continues to establish specific physiological functions. The patterns of gene expression that typify and distinguish these disparate populations, however, are mostly unknown. Here, using adult mice of mixed sex, we combined retrograde labeling of supraspinal cell nuclei with fluorescence-activated nuclei sorting and single-nuclei RNA sequencing analyses to transcriptionally profile neurons that project axons from the brain to lumbar …


All The Brain's A Stage For Serotonin: The Forgotten Story Of Serotonin Diffusion Across Cell Membranes, Paul W. Andrews, Catherine Bosyj, Luke Brenton, Laura Green, Paul J. Gasser, Christopher A. Lowry, Virginia M. Pickel Nov 2022

All The Brain's A Stage For Serotonin: The Forgotten Story Of Serotonin Diffusion Across Cell Membranes, Paul W. Andrews, Catherine Bosyj, Luke Brenton, Laura Green, Paul J. Gasser, Christopher A. Lowry, Virginia M. Pickel

Biomedical Sciences Faculty Research and Publications

In the conventional model of serotonin neurotransmission, serotonin released by neurons in the midbrain raphe nuclei exerts its actions on forebrain neurons by interacting with a large family of post-synaptic receptors. The actions of serotonin are terminated by active transport of serotonin back into the releasing neuron, which is mediated by the serotonin reuptake transporter (SERT). Because SERT is expressed pre-synaptically and is widely thought to be the only serotonin transporter in the forebrain, the conventional model does not include serotonin transport into post-synaptic neurons. However, a large body of evidence accumulating since the 1970s has shown that serotonin, despite …


Vasopressin Resets The Central Circadian Clock In A Manner Influenced By Sex And Vasoactive Intestinal Polypeptide Signaling, Kayla E. Rohr, Thomas Inda, Jennifer A. Evans Aug 2022

Vasopressin Resets The Central Circadian Clock In A Manner Influenced By Sex And Vasoactive Intestinal Polypeptide Signaling, Kayla E. Rohr, Thomas Inda, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

Background/Aims: Circadian rhythms in behavior and physiology are programmed by the suprachiasmatic nucleus (SCN) of the hypothalamus. A subset of SCN neurons produce the neuropeptide arginine vasopressin (AVP), but it remains unclear whether AVP signaling influences the SCN clock directly.

Methods: Here, we test that AVP signaling acting through V1A and V1B receptors influences molecular rhythms in SCN neurons. V1 receptor agonists were applied ex vivo to PERIOD2::LUCIFERASE SCN slices, allowing for real-time monitoring of changes in molecular clock function.

Results: V1A/B agonists reset the phase of the SCN molecular clock in a time-dependent manner, with larger magnitude responses by …


Brain-Wide Analysis Of The Supraspinal Connectome Reveals Anatomical Correlates To Functional Recovery After Spinal Injury, Zimei Wang, Adam Romanski, Vatsal Mehra, Yunfang Wang, Matthew Brannigan, Benjamin C. Campbell, Gregory A. Petsko, Pantelis Tsoulfas, Murray G. Blackmore Jul 2022

Brain-Wide Analysis Of The Supraspinal Connectome Reveals Anatomical Correlates To Functional Recovery After Spinal Injury, Zimei Wang, Adam Romanski, Vatsal Mehra, Yunfang Wang, Matthew Brannigan, Benjamin C. Campbell, Gregory A. Petsko, Pantelis Tsoulfas, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

The supraspinal connectome is essential for normal behavior and homeostasis and consists of numerous sensory, motor, and autonomic projections from brain to spinal cord. Study of supraspinal control and its restoration after damage has focused mostly on a handful of major populations that carry motor commands, with only limited consideration of dozens more that provide autonomic or crucial motor modulation. Here, we assemble an experimental workflow to rapidly profile the entire supraspinal mesoconnectome in adult mice and disseminate the output in a web-based resource. Optimized viral labeling, 3D imaging, and registration to a mouse digital neuroanatomical atlas assigned tens of …


Frontal-Cerebellar Eeg As An Index Of Risk For Alzheimer's Disease In Healthy Elders, Elizabeth Paitel Jul 2022

Frontal-Cerebellar Eeg As An Index Of Risk For Alzheimer's Disease In Healthy Elders, Elizabeth Paitel

Dissertations (1934 -)

The Apolipoprotein-E (APOE) ε4 allele is the greatest genetic risk factor for late-onset Alzheimer’s disease (AD), but alone it is not sufficiently predictive. Because neuropathological changes associated with AD begin decades before cognitive symptoms, neuroimaging of healthy, cognitively intact ε4 carriers (ε4+) may enable early characterization of neural patterns associated with risk for future cognitive decline. Research has typically focused on the cerebral cortex, where elders and ε4+ tend to exhibit ‘recruitment’ (i.e., hyperactivation) to maintain cognitive functioning. Yet, recent evidence suggests that AD-related changes may occur even earlier in the cerebellum. Moreover, advances in electroencephalography (EEG) source localization now …


Pituitary Adenylate Cyclase-Activating Polypeptide Receptor Activation In The Hypothalamus Recruits Unique Signaling Pathways Involved In Energy Homeostasis, Brian Maunze, Katherine Wood Bruckner, Nikhil Nilesh Desai, Christopher Chen, Fanghong Chen, David A. Baker, Sujean Choi Mar 2022

Pituitary Adenylate Cyclase-Activating Polypeptide Receptor Activation In The Hypothalamus Recruits Unique Signaling Pathways Involved In Energy Homeostasis, Brian Maunze, Katherine Wood Bruckner, Nikhil Nilesh Desai, Christopher Chen, Fanghong Chen, David A. Baker, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Pituitary adenylate cyclase activating polypeptide (PACAP) exerts pleiotropic effects on ventromedial nuclei (VMN) of the hypothalamus and its control of feeding and energy expenditure through the type I PAC1 receptor (PAC1R). However, the endogenous role of PAC1Rs in the VMN and the downstream signaling responsible for PACAP’s effects on energy balance are unknown. Numerous studies have revealed that PAC1Rs are coupled to both Gαs/adenylyl cyclase/protein kinase A (Gαs/AC/PKA) and Gαq/phospholipase C/protein kinase C (Gαq/PLC/PKC), while also undergoing trafficking following stimulation. To determine the endogenous role of PAC1Rs and downstream signaling that may explain PACAP’s pleiotropic effects, we used RNA interference …


Complexes Of Ghrelin Ghs-R1a, Ghs-R1b, And Dopamine D1 Receptors Localized In The Ventral Tegmental Area As Main Mediators Of The Dopaminergic Effects Of Ghrelin, Gemma Navarro, William Rea, César Quiroz, Estefanía Moreno, Devan Gomez, Cody J. Wenthur, Vicent Casadó, Lorenzo Leggio, Matthew C. Hearing, Sergi Ferré Feb 2022

Complexes Of Ghrelin Ghs-R1a, Ghs-R1b, And Dopamine D1 Receptors Localized In The Ventral Tegmental Area As Main Mediators Of The Dopaminergic Effects Of Ghrelin, Gemma Navarro, William Rea, César Quiroz, Estefanía Moreno, Devan Gomez, Cody J. Wenthur, Vicent Casadó, Lorenzo Leggio, Matthew C. Hearing, Sergi Ferré

Biomedical Sciences Faculty Research and Publications

Ghrelin receptor, also known as growth hormone secretagogue receptor (GHS-R1a), is coexpressed with its truncated isoform GHS-R1b, which does not bind ghrelin or signal, but oligomerizes with GHS-R1a, exerting a complex modulatory role that depends on its relative expression. D1 dopamine receptor (D1R) and D5R constitute the two D1-like receptor subtypes. Previous studies showed that GHS-R1b also facilitates oligomerization of GHS-R1a with D1R, conferring GHS-R1a distinctive pharmacological properties. Those include a switch in the preferred coupling of GHS-R1a from Gq to Gs and the ability of D1R/D5R agonists and antagonists to counteract GHS-R1a signaling. Activation of ghrelin …


Craniofacial Fluctuating Asymmetry In Gorillas, Chimpanzees, And Macaques, Ashly N. Romero, D. Rex Mitchell, Siobhán B. Cooke, Claire A. Kirchhoff, Claire E. Terhune Feb 2022

Craniofacial Fluctuating Asymmetry In Gorillas, Chimpanzees, And Macaques, Ashly N. Romero, D. Rex Mitchell, Siobhán B. Cooke, Claire A. Kirchhoff, Claire E. Terhune

Biomedical Sciences Faculty Research and Publications

Objectives

Craniofacial fluctuating asymmetry (FA) refers to the random deviations from symmetry exhibited across the craniofacial complex and can be used as a measure of developmental instability for organisms with bilateral symmetry. This article addresses the lack of data on craniofacial FA in nonhuman primates by analyzing FA magnitude and variation in chimpanzees, gorillas, and macaques. We offer a preliminary investigation into how FA, as a proxy for developmental instability, varies within and among nonhuman primates.

Materials and Methods

We generated 3D surface models of 121 crania from Pan troglodytes troglodytes, Gorilla gorilla gorilla, and Macaca fascicularis fascicularis …


The Anorexic Effect Of Dl-Fenfluramine Is Dependent On Animals' Habituation To Different Food Types, Sun Shin Yi, Sujean Choi Jan 2022

The Anorexic Effect Of Dl-Fenfluramine Is Dependent On Animals' Habituation To Different Food Types, Sun Shin Yi, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Background: As rates of obesity and diabetes have increased dramatically over the past few decades, the use of anti-obesity drugs has now become a routine therapeutic measure. However, the pharmacological effects of chronic use of these drugs in humans frequently lead to reduced efficacy in reducing appetite and body weight through as-yet-unidentified mechanisms. An example of this can be found in animal studies where the appetite suppressant DL-fenfluramine (FEN) is chronically administered and its tolerance develops in animals and humans. The appetite effects of FEN are typically measured in several animal studies by the feeding changes in a balanced standard …


Widening Spinal Injury Research To Consider All Supraspinal Cell Types: Why We Must And How We Can, Murray G. Blackmore, Eliazbeth Batsel, Pantelis Tsoulfas Dec 2021

Widening Spinal Injury Research To Consider All Supraspinal Cell Types: Why We Must And How We Can, Murray G. Blackmore, Eliazbeth Batsel, Pantelis Tsoulfas

Biomedical Sciences Faculty Research and Publications

The supraspinal connectome consists of dozens of neuronal populations that project axons from the brain to the spinal cord to influence a wide range of motor, autonomic, and sensory functions. The complexity and wide distribution of supraspinal neurons present significant technical challenges, leading most spinal cord injury research to focus on a handful of major pathways such as the corticospinal, rubrospinal, and raphespinal. Much less is known about many additional populations that carry information to modulate or compensate for these main pathways, or which carry pre-autonomic and other information of high value to individuals with spinal injury. A confluence of …


Modulatory Actions Of The Glycine Receptor Β Subunit On The Positive Allosteric Modulation Of Ethanol In Α2 Containing Receptors, Braulio Muñoz, Trinidad Mariqueo, Pablo Murath, Christian Peters, Gonzalo E. Yevenes, Gustavo Moraga-Cid, Robert W. Peoples, Luis G. Aguayo Nov 2021

Modulatory Actions Of The Glycine Receptor Β Subunit On The Positive Allosteric Modulation Of Ethanol In Α2 Containing Receptors, Braulio Muñoz, Trinidad Mariqueo, Pablo Murath, Christian Peters, Gonzalo E. Yevenes, Gustavo Moraga-Cid, Robert W. Peoples, Luis G. Aguayo

Biomedical Sciences Faculty Research and Publications

Alpha1-containing glycine receptors (GlyRs) are major mediators of synaptic inhibition in the spinal cord and brain stem. Recent studies reported the presence of α2-containing GlyRs in other brain regions, such as nucleus accumbens and cerebral cortex. GlyR activation decreases neuronal excitability associated with sensorial information, motor control, and respiratory functions; all of which are significantly altered during ethanol intoxication. We evaluated the role of β GlyR subunits and of two basic amino acid residues, K389 and R390, located in the large intracellular loop (IL) of the α2 GlyR subunit, which are important for binding and functional modulation by Gβγ, the …


Prelimbic Prefrontal Cortical Encoding Of Reward Predictive Cues, Mitchell Spring, Karan R. Soni, Daniel S. Wheeler, Robert A. Wheeler Aug 2021

Prelimbic Prefrontal Cortical Encoding Of Reward Predictive Cues, Mitchell Spring, Karan R. Soni, Daniel S. Wheeler, Robert A. Wheeler

Biomedical Sciences Faculty Research and Publications

Animals appoint incentive value and learn to approach otherwise behaviorally inert stimuli if these stimuli come to predict the delivery of reward. Interestingly, this adaptive Pavlovian learning process has been implicated in behavioral control disorders, such as drug addiction. One brain region implicated in directing conditioned approach behavior is the prelimbic region of the prefrontal cortex. The present study employed in vivo electrophysiology in the prelimbic cortex to characterize the distribution of neural responses to the presence of a cue that had acquired incentive value after being associated with a primary reward. Male rats were trained in a Pavlovian autoshaping …


Bolstering Geometric Morphometrics Sample Sizes With Damaged And Pathologic Specimens: Is Near Enough Good Enough?, D. Rex Mitchell, Claire A. Kirchhoff, Siobhán B. Cooke, Claire E. Terhune Jun 2021

Bolstering Geometric Morphometrics Sample Sizes With Damaged And Pathologic Specimens: Is Near Enough Good Enough?, D. Rex Mitchell, Claire A. Kirchhoff, Siobhán B. Cooke, Claire E. Terhune

Biomedical Sciences Faculty Research and Publications

Obtaining coordinate data for geometric morphometric studies often involves the sampling of dry skeletal specimens from museum collections. But many specimens exhibit damage and/or pathologic conditions. Such specimens can be considered inadequate for the analyses of shape and are excluded from study. However, the influences that damaged specimens may have on the assessment of normal shape variation have only been explored in two-dimensional coordinate data and no studies have addressed the inclusion of pathological specimens to date. We collected three-dimensional coordinate data from the cranium and mandible of 100 crab-eating macaques (Macaca fascicularis). Tests typically employed to analyze shape variation …