Medical Sciences Commons^™

Muscle Nicotinic Acetylcholine Receptors May Mediate Trans-Synaptic Signaling At The Mouse Neuromuscular Junction, Xueyong Wang, J. Michael Mcintosh, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Block of neurotransmitter receptors at the neuromuscular junction (NMJ) has been shown to trigger upregulation of the number of synaptic vesicles released (quantal content, QC), a response termed homeostatic synaptic plasticity. The mechanism underlying this plasticity is not known. Here, we used selective toxins to demonstrate that block of α1-containing nicotinic acetylcholine receptors (nAChRs) at the NMJ of male and female mice triggers the upregulation of QC. Reduction of current flow through nAChRs, induced by drugs with antagonist activity, demonstrated that reduction in synaptic current per se does not trigger upregulation of QC. These data led to the remarkable conclusion …

Trpm7 Current Inactivation: Evidence For Inside-Out Signaling, Tetyana Zhelay, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

TRPM7 channels conduct metal cations such as Na+, K+, Ca2+ and Mg2+. In the presence of external Ca2+/Mg2+ TRPM7 has a steeply outwardly rectifying current-voltage (I-V) relation. In the absence of Ca2+/Mg2+ the IV becomes semi-linear. This has been explained by the removal of pore blockade by divalent cations (e.g. Ca2+o/Mg2+o). TRPM7 channels are inhibited by cytoplasmic Mg2+ in a voltage-independent manner, primarily by a reversible reduction in the overall number of conducting channels. Here, we have examined the consequences of external Ca2+ removal and reintroduction on TRPM7 current kinetics. In whole-cell patch clamp with low internal Mg2+, we rapidly …

Inactivation Of Trpm7 Kinase In Mice Results In Enlarged Spleens, Reduced T-Cell Proliferation And Diminished Store-Operated Calcium Entry, Pavani Beesetty, Krystyna Blanka Wieczerzak, Jennifer Gibson, Taku Kaitsuka, Charles Tuan Luu, Masayuki Matsushita, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

T lymphocytes enlarge (blast) and proliferate in response to antigens in a multistep program that involves obligatory cytosolic calcium elevations. Store-operated calcium entry (SOCE) pathway is the primary source of Ca2+ in these cells. Here, we describe a novel modulator of blastogenesis, proliferation and SOCE: the TRPM7 channel kinase. TRPM7 kinase-dead (KD) K1646R knock-in mice exhibited splenomegaly and impaired blastogenic responses elicited by PMA/ionomycin or anti-CD3/CD28 antibodies. Splenic T-cell proliferation in vitro was weaker in the mutant compared to wildtype littermates. TRPM7 current magnitudes in WT and KD mouse T cells were, however, similar. We tested the dependence of T-cell …

Preliminary Understanding Of Complexities In Swimming Performance Of Common Minnow (Cyprinidae) Taxa, Crystal Nichols, Austin Smith, Stephen Huelsman, Cara Schemmel, Jason C. Doll, Stephen J. Jacquemin

Biological Sciences Faculty Publications

Understanding swimming performance of native freshwater fishes has implications for ecology, conservation, and management. In particular, this type of information has practical importance for improving the understanding of fish dispersal, occurrence, migration, and invasive potential. The objective of this study was to characterize swimming performance of 2 taxa from the comparatively understudied minnow family (Cyprinidae) and test for potential drivers as a function of total length, sex, habitat, morphology, or some combination. The study assessed Spotfin Shiner (Cyprinella spiloptera; n = 66) and Bluntnose Minnow (Pimephales notatus; n = 24) populations from an ontogenic range of male and …

A Closer Look At The Items Within Three Measures Of Evolution Acceptance: Analysis Of The Mate, I-Sea, And Gaene As A Single Corpus Of Items, William L. Romine, Amber Todd, Emily M. Walter

Biological Sciences Faculty Publications

Background

Current direct Likert measures for evolution acceptance include the MATE, GAENE, and I-SEA. Pros and cons of each of these instruments have been debated, and yet there is a dearth of research teasing out their similarities and differences when they are used together in a single context beyond the fact that their measures tend to be highly correlated. We administered these to 452 college students in non-major biology classes at two research-intensive universities from the Midwestern and Western United States to investigate the measurement properties of the items within these instruments when combined as a single corpus.

Results

Factor …

Changes In Water Quality Of Grand Lake St. Marys Watershed Following Implementation Of A Distressed Watershed Rules Package, Stephen J. Jacquemin, Laura T. Johnson, Theresa A. Dirksen, Gregory J. Mcglinch

Biological Sciences Faculty Publications

Grand Lake St. Marys watershed has drawn attention over the past decade as water quality issues resulting from nutrient loading have come to the forefront of public opinion, political concern, and scientific study. The objective of this study was to assess long-term changes in water quality (nutrient and sediment concentrations) following the distressed watershed rules package instituted in 2011. Since that time, a variety of rules (e.g., winter manure ban) and best management practices (cover crops, manure storage or transfers, buffers, etc.) have been implemented. We used a general linear model to assess variation in total suspended solids, particulate phosphorus, …

Evolutionary History Of Plant Hosts And Fungal Symbionts Predicts The Strength Of Mycorrhizal Mutualism, Jason D. Hoeksema, James D. Beaver, Sounak Chakraborty, V. Bala Chaudhary, Monique Gardes, Catherine A. Gehring, Miranda M. Hart, Elizabeth Ann Housworth, Wittaya Kaonongbua, John N. Klironomos, Marc J. Lajeunesse, James Meadow, Brook G. Milligan, Bridget J. Piculell, Anne Pringle, Megan A. Rúa, James Umbanhowar, Wolfgang Viechtbauer, Yen-Wen Wang, Gail W.T. Wilson, Peter C. Zee

Biological Sciences Faculty Publications

Most plants engage in symbioses with mycorrhizal fungi in soils and net consequences for plants vary widely from mutualism to parasitism. However, we lack a synthetic understanding of the evolutionary and ecological forces driving such variation for this or any other nutritional symbiosis. We used meta-analysis across 646 combinations of plants and fungi to show that evolutionary history explains substantially more variation in plant responses to mycorrhizal fungi than the ecological factors included in this study, such as nutrient fertilization and additional microbes. Evolutionary history also has a different influence on outcomes of ectomycorrhizal versus arbuscular mycorrhizal symbioses; the former …

Analytics For Non-Invasive Skin Imaging And Actinic Damage, Christina E. Borchers

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Modeling Virus Coinfection To Inform Management Of Maize Lethal Necrosis In Kenya, Frank H. Hilker, Linda S. J. Allen, Vrushali A. Bokil, Cheryl J. Briggs, Zhilan Feng, Karen A. Garrett, Louis J. Gross, Frédéric M. Hamelin, Michael J. Jeger, Carrie A. Manore, Alison G. Power, Margaret G. Redinbaugh, Megan A. Rúa, Nik J. Cunniffee

Biological Sciences Faculty Publications

Maize lethal necrosis (MLN) has emerged as a serious threat to food security in sub-Saharan Africa. MLN is caused by coinfection with two viruses, Maize chlorotic mottle virus and a potyvirus, often Sugarcane mosaic virus. To better understand the dynamics of MLN and to provide insight into disease management, we modeled the spread of the viruses causing MLN within and between growing seasons. The model allows for transmission via vectors, soil, and seed, as well as exogenous sources of infection. Following model parameterization, we predict how management affects disease prevalence and crop performance over multiple seasons. Resource-rich farmers with …

Characterization Of Different Molecular Markers For Identification Of Salmonella Enterica Serovar Typhi In Pakistani Population, Faizan Muttiullah, Fida Muhammad Khan, Fakhar-I- Abbas, Sabiha Shamim

Journal of Bioresource Management

Typhoid is caused by Salmonella enterica serovar Typhi that is usually diagnosed by using serologic and immuno-chromatographic techniques in developing counties including Pakistan, which is thought to be an unreliable diagnostic method. For accurate diagnosis we used molecular techniques to amplify 204 bp StyR-36 and 498 bp flagellin gene for the identification of Salmonella enterica serovar Typhi. This study was done on 58 individuals diagnosed positive of typhoid via serologic tests and 50 healthy individuals as a control group. Success rate of amplification for flagellin gene was 77.58% while that for StyR-36 gene was 68.97% showing that flagellin gene primer …

A Protocol For The Administration Of Real-Time Fmri Neurofeedback Training, Matthew Sherwood, Emily E. Diller, Elizabeth Ey, Subhashini Ganapathy, Jeremy T. Nelson, Jason G. Parker

Neuroscience, Cell Biology & Physiology Faculty Publications

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control neuroplastic processes and correct abnormal function, or even shift functions from damaged tissue to physiologically healthy brain regions, hold the potential to dramatically improve overall health. Of the current neuroplastic interventions in development, neurofeedback training (NFT) from functional Magnetic Resonance Imaging (fMRI) has the advantages of being completely non-invasive, non-pharmacologic, and spatially localized to target brain regions, as well as having no known side effects. Furthermore, NFT techniques, initially developed using fMRI, can often be translated to exercises that can …

Mixed-Mode Oscillations In Pyramidal Neurons Under Antiepileptic Drug Conditions, Babak V-Ghaffari, M. Kouhnavard, Sherif M. Elbasiouny

Neuroscience, Cell Biology, & Physiology Faculty Publications

Subthreshold oscillations in combination with large-amplitude oscillations generate mixedmode oscillations (MMOs), which mediate various spatial and temporal cognition and memory processes and behavioral motor tasks. Although many studies have shown that canard theory is a reliable method to investigate the properties underlying the MMOs phenomena, the relationship between the results obtained by applying canard theory and conductancebased models of neurons and their electrophysiological mechanisms are still not well understood. The goal of this study was to apply canard theory to the conductance-based model of pyramidal neurons in layer V of the Entorhinal Cortex to investigate the properties of MMOs under …

Injury-Induced Microvesicle Particle Release In Human Skin Explant Tissue, Katherine E. Fahy, Langni Liu, Christine M. Rapp, Eric J. Romer, Christina E. Borchers, Richard Simman, Ji C. Bihl, Jeffrey B. Travers

Pharmacology and Toxicology Faculty Publications

Microvesicle particles (MVP) are 100-1000 nm vesicles that bud from the cell membrane and transmit intercellular signals locally and systemically via their bioactive cargo (e.g. cytokines).

Injury-Induced Microvesicle Particle Release In Human Skin Explant Tissue, Katherine E. Fahy, Langni Liu, Christina E. Borchers, Richard Simman, Ji C. Bihl, Jeffrey B. Travers

Pharmacology and Toxicology Faculty Publications

Microvesicle particles (MVP) are 100-1000 nm vesicles that bud from the cell membrane and transmit intercellular signals locally and systemically via their bioactive cargo (e.g. cytokines). We have previously shown that thermal burn injury or UVB radiation result in the formation Platelet Activating Factor (PAF), and UVB or a PAF agonist (CPAF) can promote MVP formation in keratinocytes. Thermal burn and UVB radiation can result in systemic effects, even though their injury is localized to the skin. We therefore propose that PAF-producing injuries, UVB irradiation or thermal burn injury, result in the formation of MVPs that can potentially transport cytokines …

Proceedings - Wright State University Boonshoft School Of Medicine Ninth Annual Medical Student Research Symposium: Celebrating Medical Student Scholarship, Office Of Research Affairs, Boonshoft School Of Medicine

Medical Student Research Symposium Proceedings

The student abstract booklet is a compilation of abstracts from students' oral and poster presentations at Wright State University's Ninth Annual Boonshoft School of Medicine Medical Student Research Symposium held on April 12, 2017.

A Review Of The Role Of Interleukin-6 On Disease Progression In Epithelial Ovarian Cancer, Urmimala Chaudhuri

Browse all Theses and Dissertations

Ovarian cancer is one of the most harmful gynecological cancers and has one of the highest mortality rates. As ovarian cancer progresses, the patient has changes to the immune system and energy metabolism with symptoms being weight loss, nausea, and fatigue. Changes to the immune system include overexpression of proinflammatory cytokines. One such cytokine is Interleukin-6 (IL-6), which is a useful prognostic marker to measure disease progression. IL-6 is thought to promote cancer cell proliferation by upregulating apoptosis inhibitory proteins. IL-6 also plays a role in ascites formation. While tumors may initially respond to chemotherapy treatment, most patients will have …

Glioma Stem Cells-Derived Exosomes Promote The Angiogenic Ability Of Endothelial Cells Through Mir-21/Vegf Signal, Xu Sun, Xiaotang Ma, Jinju Wang, Yuhui Zhao, Yue Wang, Ji C. Bihl, Yanfang Chen, Chuanlu Jiang

Pharmacology and Toxicology Faculty Publications

Glioma stem cells (GSCs) play an important role in glioblastoma prognosis. Exosomes (EXs) mediate cell communication by delivering microRNAs (miRs). Glioblastoma has a high level of miR-21 which could upregulate vascular endothelial growth factor (VEGF) expression. We hypothesized GSC-EXs can promote the angiogenic ability of endothelial cells (ECs) through miR-21/VEGF signal. GSCs were isolated from U-251 cells with stem cell marker CD133. GSCs transfected without or with scramble or miR-21 mimics were used to produce GSC-^EXscon, GSC-EXs^sc and GSC-EXs^miR-21. Human brain ECs were co-cultured with vehicle, GSC-EXs^con, GSC-EXs^sc or GSC-EXs^miR-21 plus …

Regulation Of Trpm7 By Cytosolic Mg2+ And Ph: Insights From Vsp Expression, Pavani Beesetty, Krystyna Blanka Wieczerzak, Tatyana Zhelay, Taku Kaitsuka, Masayuki Matsushita, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

TRPM7 is an ion channel/protein kinase belonging to TRP melastatin and eEF2 kinase families. Under physiological conditions, most native TRPM7 channels are inactive, due to inhibition by cytoplasmic Mg2+, protons and polyamines. ITRPM7 is strongly potentiated when cell cytosol is depleted of Mg2+ or alkalinized. In Jurkat T cells, Mg2+ inhibition involves a high and a low affinity inhibitor sites, whereas proton inhibition involves only one site. Like many other TRP channels, TRPM7 is activated by PI(4,5)P2 and suppressed by its hydrolysis. Here we examined Mg2+ and pH inhibition of native TRPM7 channels in HEK293 cells overexpressing voltage-sensitive phospholipid phosphatase …

Analysis Of Proprioceptive Sensory Innervation Of The Mouse Soleus: A Whole-Mount Muscle Approach, Martha Jean Sonner, Marie C. Walters, David R. Ladle

Neuroscience, Cell Biology & Physiology Faculty Publications

Muscle proprioceptive afferents provide feedback critical for successful execution of motor tasks via specialized mechanoreceptors housed within skeletal muscles: muscle spindles, supplied by group Ia and group II afferents, and Golgi tendon organs, supplied by group Ib afferents. The morphology of these proprioceptors and their associated afferents has been studied extensively in the cat soleus, and to a lesser degree, in the rat; however, quantitative analyses of proprioceptive innervation in the mouse soleus are comparatively limited. The present study employed genetically-encoded fluorescent reporting systems to label and analyze muscle spindles, Golgi tendon organs, and the proprioceptive sensory neuron subpopulations supplying …

Survival And Growth Of C57bl/6j Mice Lacking The Bk Channel, Kcnma1: Lower Adult Body Weight Occurs Together With Higher Body Fat, Susan T. Halm, Michael A. Bottomley, Mohammed M. Almutairi, Mauricio Di Fulvio, Dan R. Halm

Neuroscience, Cell Biology & Physiology Faculty Publications

Big conductance potassium (BK) channels contribute to K⁺ flow and electrical behavior in many cell types. Mice made null for the gene (Kcnma1) producing the BK channel (BK^KO) exhibit numerous deficits in physiological functions. Breeding mice lacking a single allele of Kcnma1 (C57BL/6J background) had litter sizes of approximately eight pups. For the period of maternal care (P0– P21), pup deaths peaked at P1 with a second less severe interval of death peaking near P13. Early deaths were twice as likely during a 20-month period of building construction compared with the quiescent period after cessation of construction. Births …

Evidence Of Morphological And Functional Variation Among Bluegill Lepomis Macrochirus Populations Across Grand Lake St Mary's Watershed Area, Anthony Bell, Stephen J. Jacquemin

Biological Sciences Faculty Publications

A myriad of factors have been shown to influence the morphology offreshwaterfish. However, studies that parse out where variation is comingfrom (e.g. body size, sex, and habitat) as well as what potential thesechanges have to influence function (e.g. swimming performance) areunderstudied. Therefore, the objectives of this study were to describemorphological variation of BluegillLepomis macrochirusacross the GrandLake St Mary’s watershed area (northwest OH, USA) and test forcovariation of morphology with size, sex, and habitat as well as to assessswimming performance to discern whether any differences in habitat (andmorphology) correspond with functional aspects related to criticalswimming velocity. Geometric morphometric methods were used …

First Definitive Fossil Of An Oestroid Fly (Diptera: Calyptratae: Oestroidea) And The Dating Of Oestroid Divergences, Pierfilippo Cerretti, John O. Stireman Iii, Thomas Pape, James E. O'Hara, Marco A. Marinho, Knut Rognes, David A. Grimaldi

Biological Sciences Faculty Publications

Calyptrate flies include about 22,000 extant species currently classified into Hippoboscoidea (tsetse, louse, and bat flies), the muscoid grade (house flies and relatives) and the Oestroidea (blow flies, bot flies, flesh flies, and relatives). Calyptrates are abundant in nearly all terrestrial ecosystems, often playing key roles as decomposers, parasites, parasitoids, vectors of pathogens, and pollinators. For oestroids, the most diverse group within calyptrates, definitive fossils have been lacking. The first unambiguous fossil of Oestroidea is described based on a specimen discovered in amber from the Dominican Republic. The specimen was identified through digital dissection by CT scans, which provided morphological …

Uvb Induces Mvp Release In A Paf Dependent Manner In Skin-Dervied Epithelial Cell Line, Langni Liu, Katherine E. Fahy, Christine M. Rapp, Eric J. Romer, Christina E. Borchers, Ji C. Bihl, Jeffrey B. Travers

Pharmacology and Toxicology Faculty Publications

Ultraviolet-B (UVB) irradiation of the skin can result in both acute inflammation and systemic immunosuppression. These effects are mediated by the release of bioactive molecules (e.g. cytokines and lipids) from resident skin epithelial and immune cells. Our lab has previously determined that UVB exposure stimulates the production of an inflammatory phospholipid activator, platelet-activating factor (PAF) and its oxidized analogs, which are involved in mediating the UVB responses. Due to the fact that UVB radiation is absorbed by the epidermis but causes systemic effects, we are interested in examining the PAF-mediated mechanisms of systemic intercellular communication. Microvesicle particles (MVP) are small …

Intercellular Adhesion Molecule-1 Augments Myoblast Adhesion And Fusion Through Homophilic Trans-Interactions, Francis X. Pizza, Ryan A. Martin, Evan M. Springer, Maxwell S. Leffler, Bryce R. Woelmer, Issac J. Recker, Douglas W. Leaman

Biological Sciences Faculty Publications

The overall objective of the study was to identify mechanisms through which intercellular adhesion molecule-1 (ICAM-1) augments the adhesive and fusogenic properties of myogenic cells. Hypotheses were tested using cultured myoblasts and fibroblasts, which do not constitutively express ICAM-1, and myoblasts and fibroblasts forced to express full length ICAM-1 or a truncated form lacking the cytoplasmic domain of ICAM-1. ICAM-1 mediated myoblast adhesion and fusion were quantified using novel assays and cell mixing experiments. We report that ICAM-1 augments myoblast adhesion to myoblasts and myotubes through homophilic trans-interactions. Such adhesive interactions enhanced levels of active Rac in adherent and …

Synaptic Up-Scaling Preserves Motor Circuit Output After Chronic, Natural Inactivity, Joseph Michael Santin, Mauricio Vallejo, Lynn K. Hartzler

Biological Sciences Faculty Publications

Neural systems use homeostatic plasticity to maintain normal brain functions and to prevent abnormal activity. Surprisingly, homeostatic mechanisms that regulate circuit output have mainly been demonstrated during artificial and/or pathological perturbations. Natural, physiological scenarios that activate these stabilizing mechanisms in neural networks of mature animals remain elusive. To establish the extent to which a naturally inactive circuit engages mechanisms of homeostatic plasticity, we utilized the respiratory motor circuit in bullfrogs that normally remains inactive for several months during the winter. We found that inactive respiratory motoneurons exhibit a classic form of homeostatic plasticity, up-scaling of AMPA-glutamate receptors. Up-scaling increased the …

Insights Into The Ecology, Genetics And Distribution Of Lucanus Elaphus Fabricius (Coleoptera: Lucanidae), North America's Giant Stag Beetle, Michael D. Ulyshen, Louis G. Zachos, John O. Stireman Iii, Thomas N. Sheehan, Ryan C. Garrick

Biological Sciences Faculty Publications

1. Little is known about the biology or conservation status of Lucanus elaphus Fabricius in North America despite well-documented declines of a related species, Lucanus cervus (L.), in Europe. This study provides information critical to developing conservation plans for L. elaphus including the species’ larval substrate requirements, genetic data and range-wide estimates of habitat suitability. 2. In Mississippi floodplain forests, larval L. elaphus were recovered from a wide range of log sizes and rot types and were either found tunnelling within the wood or feeding beneath logs at the soil–wood interface. The species appears to require 1–2 years to complete …

Neprilysin Is A Mediator Of Alternative Renin-Angiotensin-System Activation In The Murine And Human Kidney, Oliver Domenig, Arndt Manzel, Nadja Grobe, Eva Königshausen, Christopher C. Kaltenecker, Johannes J. Kovarik, Susan B. Gurley, Dunja Van Oyen, Marlies Antlanger, Michael Bader, Daisy Motta-Santos, Jose Carlos Santos, Robson A. Santos, Khalid M. Elased, Marcus D. Säemann, Ralf A. Linker, Marko Poglitsch

Pharmacology and Toxicology Faculty Publications

Cardiovascular and renal pathologies are frequently associated with an activated renin-angiotensin-system (RAS) and increased levels of its main effector and vasoconstrictor hormone angiotensin II (Ang II). Angiotensin-converting-enzyme-2 (ACE2) has been described as a crucial enzymatic player in shifting the RAS towards its so-called alternative vasodilative and reno-protective axis by enzymatically converting Ang II to angiotensin-(1-7) (Ang-(1-7)). Yet, the relative contribution of ACE2 to Ang-(1-7) formation in vivo has not been elucidated. Mass spectrometry based quantification of angiotensin metabolites in the kidney and plasma of ACE2 KO mice surprisingly revealed an increase in Ang-(1-7), suggesting additional pathways to be responsible for …

Reduced Motor Neuron Excitability Is An Important Contributor To Weakness In A Rat Model Of Sepsis, Paul Nardelli, Jacob A. Vincent, Randall K. Powers, Timothy C. Cope, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

The mechanisms by which sepsis triggers intensive care unit acquired weakness (ICUAW) remain unclear. We previously identified difficulty with motor unit recruitment in patients as a novel contributor to ICUAW. To study the mechanism underlying poor recruitment of motor units we used the rat cecal ligation and puncture model of sepsis. We identified striking dysfunction of alpha motor neurons during repetitive firing. Firing was more erratic, and often intermittent. Our data raised the possibility that reduced excitability of motor neurons was a significant contributor to weakness induced by sepsis. In this study we quantified the contribution of reduced motor neuron …

Combining Real-Time Fmri Neurofeedback Training Of The Dlpfc With N-Back Practice Results In Neuroplastic Effects Confined To The Neurofeedback Target Region, Matthew Sherwood, Michael P. Weisend, Jessica H. Kane, Jason G. Parker

Neuroscience, Cell Biology & Physiology Faculty Publications

In traditional fMRI, individuals respond to exogenous stimuli and are naïve to the effects of the stimuli on their neural activity patterns. Changes arising in the fMRI signal are analyzed post-hoc to elucidate the spatial and temporal activation of brain regions associated with the tasks performed. The advent of real-time fMRI has enabled a new method to systematically alter brain activity across space and time using neurofeedback training (NFT), providing a new tool to study internally-driven processes such as neuroplasticity. In this work, we combined n-back practice with fMRI-NFT of the left dorsolateral prefrontal cortex (DLPFC) to better understand the …

Synapse Formation In Monosynaptic Sensory–Motor Connections Is Regulated By Presynaptic Rho Gtpase Cdc42, Fumiyasu Imai, David R. Ladle, Jennifer R. Leslie, Xin Duan, Tilat A. Rizvi, Georgianne M. Ciraolo, Yi Zheng, Yutaka Yoshida

Neuroscience, Cell Biology & Physiology Faculty Publications

Spinal reflex circuit development requires the precise regulation of axon trajectories, synaptic specificity, and synapse formation. Of these three crucial steps, the molecular mechanisms underlying synapse formation between group Ia proprioceptive sensory neurons and motor neurons is the least understood. Here, we show that the Rho GTPase Cdc42 controls synapse formation in monosynaptic sensory–motor connections in presynaptic, but not postsynaptic, neurons. In mice lacking Cdc42 in presynaptic sensory neurons, proprioceptive sensory axons appropriately reach the ventral spinal cord, but significantly fewer synapses are formed with motor neurons compared with wild-type mice. Concordantly, electrophysiological analyses show diminished EPSP amplitudes in monosynaptic …