Medicine and Health Sciences Commons^™

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

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

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

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

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 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

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

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

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 …