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Full-Text Articles in Neurosciences

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 …


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 …


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 …


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 …


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 …


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 …


Chronic Stress Prevents Cortico-Accumbens Cue Encoding And Alters Conditioned Approach, Mitchell Spring, Aaron Caccamise, Elizabeth A. Panther, Bethany M. Windsor, Karan R. Soni, Jayme R. Mcreynolds, Daniel S. Wheeler, John R. Mantsch, Robert A. Wheeler Mar 2021

Chronic Stress Prevents Cortico-Accumbens Cue Encoding And Alters Conditioned Approach, Mitchell Spring, Aaron Caccamise, Elizabeth A. Panther, Bethany M. Windsor, Karan R. Soni, Jayme R. Mcreynolds, Daniel S. Wheeler, John R. Mantsch, Robert A. Wheeler

Biomedical Sciences Faculty Research and Publications

Chronic stress impairs the function of multiple brain regions and causes severe hedonic and motivational deficits. One brain region known to be susceptible to these effects is the PFC. Neurons in this region, specifically neuronal projections from the prelimbic region (PL) to the nucleus accumbens core (NAcC), have a significant role in promoting motivated approach. However, little is known about how activity in this pathway changes during associative learning to encode cues that promote approach. Less is known about how activity in this pathway may be altered by stress. In this study, an intersectional fiber photometry approach was used in …


Intracellular Β1-Adrenergic Receptors And Organic Cation Transporter 3 Mediate Phospholamban Phosphorylation To Enhance Cardiac Contractility, Ying Wang, Qian Shi, Minghui Li, Meimi Zhao, Raghavender Reddy Gopireddy, Jian-Peng Teoh, Bing Xu, Chaoqun Zhu, Kyle E. Ireton, Sanghavi Srinivasan, Shaoliang Chen, Paul J. Gasser, Julie Bossuyt, Johannes W. Hell, Donald M. Bers, Yang K. Xiang Jan 2021

Intracellular Β1-Adrenergic Receptors And Organic Cation Transporter 3 Mediate Phospholamban Phosphorylation To Enhance Cardiac Contractility, Ying Wang, Qian Shi, Minghui Li, Meimi Zhao, Raghavender Reddy Gopireddy, Jian-Peng Teoh, Bing Xu, Chaoqun Zhu, Kyle E. Ireton, Sanghavi Srinivasan, Shaoliang Chen, Paul J. Gasser, Julie Bossuyt, Johannes W. Hell, Donald M. Bers, Yang K. Xiang

Biomedical Sciences Faculty Research and Publications

Rationale:

β1ARs (β1-adrenoceptors) exist at intracellular membranes and OCT3 (organic cation transporter 3) mediates norepinephrine entry into cardiomyocytes. However, the functional role of intracellular β1AR in cardiac contractility remains to be elucidated.

Objective:

Test localization and function of intracellular β1AR on cardiac contractility.

Methods and Results:

Membrane fractionation, super-resolution imaging, proximity ligation, coimmunoprecipitation, and single-molecule pull-down demonstrated a pool of β1ARs in mouse hearts that were associated with sarco/endoplasmic reticulum Ca2+-ATPase at the sarcoplasmic reticulum (SR). Local PKA (protein kinase A) activation was measured using a PKA biosensor …


Vasopressin Regulates Daily Rhythms And Circadian Clock Circuits In A Manner Influenced By Sex, Kayla Rohr, Adam Telega, Alexandra Savaglio, Jennifer A. Evans Jan 2021

Vasopressin Regulates Daily Rhythms And Circadian Clock Circuits In A Manner Influenced By Sex, Kayla Rohr, Adam Telega, Alexandra Savaglio, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

Arginine vasopressin (AVP) is a neurohormone that alters cellular physiology through both endocrine and synaptic signaling. Circadian rhythms in AVP release and other biological processes are driven by the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. Loss of vasopressin signaling alters circadian behavior, but the basis of these effects remains unclear. Here we investigate the role of AVP signaling in circadian timekeeping by analyzing behavior and SCN function in a novel AVP-deficient mouse model. Consistent with previous work, loss of AVP signaling increases water consumption and accelerates recovery to simulated jetlag. We expand on these results to show that loss …


Organic Cation Transporter 3 And The Dopamine Transporter Differentially Regulate Catecholamine Uptake In The Basolateral Amygdala And Nucleus Accumbens, Katherine M. Holleran, Jamie H. Rose, Steven C. Fordahl, Kelsey C. Benton, Kayla E. Rohr, Paul J. Gasser, Sara R. Jones Dec 2020

Organic Cation Transporter 3 And The Dopamine Transporter Differentially Regulate Catecholamine Uptake In The Basolateral Amygdala And Nucleus Accumbens, Katherine M. Holleran, Jamie H. Rose, Steven C. Fordahl, Kelsey C. Benton, Kayla E. Rohr, Paul J. Gasser, Sara R. Jones

Biomedical Sciences Faculty Research and Publications

Regional alterations in kinetics of catecholamine uptake are due in part to variations in clearance mechanisms. The rate of clearance is a critical determinant of the strength of catecholamine signaling. Catecholamine transmission in the nucleus accumbens core (NAcc) and basolateral amygdala (BLA) is of particular interest due to involvement of these regions in cognition and motivation. Previous work has shown that catecholamine clearance in the NAcc is largely mediated by the dopamine transporter (DAT), but clearance in the BLA is less DAT‐dependent. A growing body of literature suggests that organic cation transporter 3 (OCT3) also contributes to catecholamine clearance in …


Marking Time: Colorful New Insights Into Master Clock Circuits, Deborah A.M. Joye, Jennifer A. Evans Oct 2020

Marking Time: Colorful New Insights Into Master Clock Circuits, Deborah A.M. Joye, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

No abstract provided.


Neurotoxicity Of Isomers Of The Environmental Toxin L-Bmaa, Thomas Schneider, Catherine Simpson, Prachi Desai, Madeleine Tucker, Doug Lobner Sep 2020

Neurotoxicity Of Isomers Of The Environmental Toxin L-Bmaa, Thomas Schneider, Catherine Simpson, Prachi Desai, Madeleine Tucker, Doug Lobner

Biomedical Sciences Faculty Research and Publications

There is evidence that the environmental toxin β-N-methylamino-L-alanine (L-BMAA) may be involved in neurodegenerative diseases. However, a number of controversies exist regarding L-BMAA, one of which is the possibility that when assaying for L-BMAA, its isomers are being detected instead. There are at least four isomers of BMAA that are known to occur: L-BMAA, β-N-methylamino-D-alanine (D-BMAA), 2,4-diaminobutyric acid (DAB), and N-(2-aminoethyl)glycine (AEG). The fact that isomers of BMAA exist in nature also leads to the possibility that they are involved in toxicity. We set out to determine both the potency and the mechanism of toxicity of L-BMAA, D-BMAA, DAB, and …


Reduced Vip Expression Affects Circadian Clock Function In Vip-Ires-Cre Mice (Jax 010908), Deborah A.M. Joye, Kayla Rohr, Danielle Keller, Thomas Inda, Adam Telega, Harshida Pancholi, Vania Carmonia-Alcocer, Jennifer A. Evans Aug 2020

Reduced Vip Expression Affects Circadian Clock Function In Vip-Ires-Cre Mice (Jax 010908), Deborah A.M. Joye, Kayla Rohr, Danielle Keller, Thomas Inda, Adam Telega, Harshida Pancholi, Vania Carmonia-Alcocer, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

Circadian rhythms are programmed by the suprachiasmatic nucleus (SCN), which relies on neuropeptide signaling to maintain daily timekeeping. Vasoactive intestinal polypeptide (VIP) is critical for SCN function, but the precise role of VIP neurons in SCN circuits is not fully established. To interrogate their contribution to SCN circuits, VIP neurons can be manipulated specifically using the DNA-editing enzyme Cre recombinase. Although the Cre transgene is assumed to be inert by itself, we find that VIP expression is reduced in both heterozygous and homozygous adult VIP-IRES-Cre mice (JAX 010908). Compared with wild-type mice, homozygous VIP-Cre mice display faster reentrainment and shorter …


Prelimbic Input To Basolateral Amygdala Facilitates The Acquisition Of Trace Cued Fear Memory Under Weak Training Conditions, Adam Kirry, Robert C. Twining, Marieke R. Gilmartin Jul 2020

Prelimbic Input To Basolateral Amygdala Facilitates The Acquisition Of Trace Cued Fear Memory Under Weak Training Conditions, Adam Kirry, Robert C. Twining, Marieke R. Gilmartin

Biomedical Sciences Faculty Research and Publications

The ability to predict the occurrence of an aversive outcome based on available cues requires associative learning and plastic changes in the amygdala. When the predictive cue and aversive shock outcome are separated in time as in trace fear conditioning, additional circuitry is needed, including the prelimbic (PL) area of the prefrontal cortex. We have previously shown that neuronal firing in the PL during the trace interval separating the cue and shock is required for trace cued fear memory formation, but whether this mnemonic signal is conveyed to the amygdala is unknown. Here we show in males that silencing PL …