Medicine and Health Sciences Commons^™

The Scripps Research Institute Summer Undergraduate Research Fellowship, Ezana Assefa

Trick to the Treat of Internships and Research

This program is a 10-week internship designed for undergraduates interested in the scientific field to engage in current research. Students have the option of requesting to work under three mentors, one of which they will be paired. Students will work in the lab with the principal investigator and other members of the lab. Along with working in the lab, students in the program will also attend bi-weekly talks/lectures from researchers, grad students, and professionals at TSRI as well as participating in two presentations and a final poster or oral presentation.

Interleukin-17a Promotes Cd8 T Cell Cytotoxicity To Facilitate West Nile Virus Clearance, Amber M. Paul, Dhiraj Acharya, Penghua Wang, Jianfeng Dai, David Gate

Publications

CD8 T cells are crucial components of immunity and play a vital role in recovery from West Nile virus (WNV) infection. Here, we identify a previously unrecognized function of interleukin-17A (IL-17A) in inducing cytotoxic-mediator gene expression and promoting CD8 T cell cytotoxicity against WNV infection in mice. We find that IL-17A-deficient (Il17a/) mice are more susceptible to WNV infection and develop a higher viral burden than wild-type (WT) mice. Interestingly, the CD8 T cells isolated from Il17a/ mice are less cytotoxic and express lower levels of cytotoxic-mediator genes, which can be restored by supplying recombinant IL-17A in vitro and in …

Usage Of Swi (Susceptibility Weighted Imaging) Acquired At 7t For Qualitative Evaluation Of Temporal Lobe Epilepsy Patients With Histopathological And Clinical Correlation: An Initial Pilot Study., Benjamin Y M Kwan, Fateme Salehi, Pavlo Ohorodnyk, Donald H Lee, Jorge G Burneo, Seyed M Mirsattari, David Steven, Robert Hammond, Terry M Peters, Ali R Khan

Brain and Mind Institute Researchers' Publications

OBJECTIVES: Ultra high field MRI at 7T is able to provide much improved spatial and contrast resolution which may aid in the diagnosis of hippocampal abnormalities. This paper presents a preliminary experience on qualitative evaluation of 7T MRI in temporal lobe epilepsy patients with a focus on comparison to histopathology.

METHODS: 7T ultra high field MRI data, using T1-weighted, T2*-weighted and susceptibility-weighted images (SWI), were acquired for 13 patients with drug resistant temporal lobe epilepsy (TLE) during evaluation for potential epilepsy surgery. Qualitative evaluation of the imaging data for scan quality and presence of hippocampal and temporal lobe abnormalities were …

Quantifying And Comparing The Pattern Of Thalamic And Cortical Projections To The Posterior Auditory Field In Hearing And Deaf Cats., Blake E Butler, Nicole Chabot, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

Following sensory loss, compensatory crossmodal reorganization occurs such that the remaining modalities are functionally enhanced. For example, behavioral evidence suggests that peripheral visual localization is better in deaf than in normal hearing animals, and that this enhancement is mediated by recruitment of the posterior auditory field (PAF), an area that is typically involved in localization of sounds in normal hearing animals. To characterize the anatomical changes that underlie this phenomenon, we identified the thalamic and cortical projections to the PAF in hearing cats and those with early- and late-onset deafness. The retrograde tracer biotinylated dextran amine was deposited in the …

Fumarate Modulates The Immune/Inflammatory Response And Rescues Nerve Cells And Neurological Function After Stroke In Rats., Ruihe Lin, Jingli Cai, Eric W Kostuk, Robert H. Rosenwasswer Md, Lorraine Iacovitti

Farber Institute for Neuroscience Faculty Papers

BACKGROUND: Dimethyl fumarate (DMF), working via its metabolite monomethylfumarate (MMF), acts as a potent antioxidant and immunomodulator in animal models of neurologic disease and in patients with multiple sclerosis. These properties and their translational potential led us to investigate whether DMF/MMF could also protect at-risk and/or dying neurons in models of ischemic stroke in vitro and in vivo. Although the antioxidant effects have been partially addressed, the benefits of DMF immunomodulation after ischemic stroke still need to be explored.

METHODS: In vitro neuronal culture with oxygen-glucose deprivation and rats with middle cerebral artery occlusion were subjected to DMF/MMF treatment. Live/dead …

Professional Action Sport Athletes’ Experiences With And Attitudes Toward Concussion: A Phenomenological Study, Caroline E. Faure, John M. Fitzpatrick

The Qualitative Report

This study examined the lived experiences and subsequent attitudes of freestyle BMX and motocross athletes relative to suffering concussions. Eleven professional athletes were interviewed using a semi-structured protocol. All cited a significant personal history with concussion and those personal accounts, along with their observations of others who experienced similar head injuries, shaped the athletes’ attitudes towards concussion. Both intrinsic and extrinsic factors contributed to each athlete’s acceptance of concussion risk inherent in their respective sport. Generally, athletes accepted concussion risk as part of their sport, but were largely unfamiliar with what concussion was and what long-term effects could result from …

Neural Measures Reveal Implicit Learning During Language Processing., Laura J Batterink, Larry Y Cheng, Ken A Paller

Brain and Mind Institute Researchers' Publications

Language input is highly variable; phonological, lexical, and syntactic features vary systematically across different speakers, geographic regions, and social contexts. Previous evidence shows that language users are sensitive to these contextual changes and that they can rapidly adapt to local regularities. For example, listeners quickly adjust to accented speech, facilitating comprehension. It has been proposed that this type of adaptation is a form of implicit learning. This study examined a similar type of adaptation, syntactic adaptation, to address two issues: (1) whether language comprehenders are sensitive to a subtle probabilistic contingency between an extraneous feature (font color) and syntactic structure …

Intravenous Prenatal Nicotine Exposure Alters Meth-Induced Hyperactivity, Conditioned Hyperactivity, And Bdnf In Adult Rat Offspring, Ryan T. Lacy, Russell. W. Brown, Amanda J. Morgan, Charles F. Mactutus, Steven B. Harrod

ETSU Faculty Works

In the USA, approximately 15% of women smoke tobacco cigarettes during pregnancy. In utero tobacco smoke exposure produces somatic growth deficits like intrauterine growth restriction and low birth we

Assessment Of The Effects Of Mptp And Paraquat On Dopaminergic Neurons And Microglia In The Substantia Nigra Pars Compacta Of C57bl/6 Mice., Richard Jay Smeyne, Charles B. Breckenridge, Melissa Beck, Yun Jiao, Mark T. Butt, Jeffrey C. Wolf, Dan Zadory, Daniel J. Minnema, Nicholas C. Sturgess, Kim Z. Travis, Andrew R. Cook, Lewis L. Smith, Philip A. Botham

Department of Neuroscience Faculty Papers

The neurotoxicity of paraquat dichloride (PQ) was assessed in two inbred strains of 9- or 16-week old male C57BL/6 mice housed in two different laboratories and compared to the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). PQ was administered by intraperitoneal injections; either once (20 mg/kg) or twice (10 mg/kg) weekly for 3 weeks, while MPTP-HCl was injected 4 times on a single day (20 mg/kg/dose). Brains were collected 8, 16, 24, 48, 96 or 168 hours after the last PQ treatment, and 48 or 168 hours after MPTP treatment. Dopamine neurons in the substantia nigra pars compacta (SNpc) were identified by antibodies …

Structural Dichotomy Of The Mind; The Role Of Sexual Neuromodulators, Ion G. Motofei, David L. Rowland

Journal of Mind and Medical Sciences

The mind (mental function) and sexuality represent two distinct environmental functions, but which are supported within the brain by a common (somatic-autonomic) neurobiological substrate. As a consequence, mental function takes on autonomic characteristics from the sexual-autonomic system (like autonomy, duality), while sexual function takes on features from mental functioning (such as lateralization). In this paper we discuss the lateralized action of two classes of sexual neuromodulators: hormones and pheromones. This process of lateralization is assimilated with the structural dichotomy of the mind.

A relatively similar process but related to informational dichotomy of the mind will be presented in a forthcoming …

The Substrate Of The Biopsychosocial Influences In The Carcinogenesis Of The Digestive Tract, Georgică C. Târtea, Cristina Florescu, Daniel Pirici, Daniel Caragea, Elena A. Târtea, Cristin C. Vere

Journal of Mind and Medical Sciences

Digestive cancer represents a severe public health problem, being one of the main causes of death. It is considered a multifactorial disease, with hereditary predisposition, environmental factors, and other factors involved in carcinogenesis. Both the evolution and the pathogenesis of digestive neoplasms remain incompletely elucidated. As a multifactorial disease, it can be approached by taking into account the biopsychosocial influences via enteric nervous system. Many peptides and non-peptides having a neurotransmitter role can be found in the enteric nervous system, which can influence the neoplastic process directly or indirectly by affecting some angiogenic, growth, and metastasis factors. However, neurotransmitters can …

The Postfinasteride Syndrome; An Overview, David L. Rowland, Ion G. Motofei, Florian Popa, Vlad D. Constantin, Adriana Vasilache, Ioana Păunică, Cristian Bălălău, Georgeta P. Păunică, Petrisor Banu, Stana Păunică

Journal of Mind and Medical Sciences

As a 5-α reductase inhibitor, Finasteride has proven effective in ameliorating two conditions documented to be androgen dependent, namely male androgenic alopecia and benign prostatic hyperplasia. Therapeutic results are maintained as long as the drug is administered, with treatment cessation generally leading to the return of symptomatology for each condition. In addition, during the therapeutic phase, several adverse effects have been reported, some of which persist long or indefinitely after treatment cessation, known as “post-finasteride syndrome.”

Herein we present and discuss the most common finasteride side effects, along with a psycho-neuroendocrine rationale that could explain the persistence of many adverse …

Immunomodulators As Therapeutic Agents In Mitigating The Progression Of Parkinson's Disease, Bethany Grimmig, Josh Morganti, Kevin Nash, Paula C. Bickford

Sanders-Brown Center on Aging Faculty Publications

Parkinson’s disease (PD) is a common neurodegenerative disorder that primarily afflicts the elderly. It is characterized by motor dysfunction due to extensive neuron loss in the substantia nigra pars compacta. There are multiple biological processes that are negatively impacted during the pathogenesis of PD, and are implicated in the cell death in this region. Neuroinflammation is evidently involved in PD pathology and mitigating the inflammatory cascade has been a therapeutic strategy. Age is the number one risk factor for PD and thus needs to be considered in the context of disease pathology. Here, we discuss the role of neuroinflammation within …

Tau Phosphorylation At Alzheimer's Disease-Related Ser356 Contributes To Tau Stabilization When Par-1/Mark Activity Is Elevated., Kanae Ando, Mikiko Oka, Yosuke Ohtake, Motoki Hayashishita, Sawako Shimizu, Shin-Ichi Hisanaga, Koichi M. Iijima

Department of Neuroscience Faculty Papers

Abnormal phosphorylation of the microtubule-associated protein tau is observed in many neurodegenerative diseases, including Alzheimer's disease (AD). AD-related phosphorylation of two tau residues, Ser262 and Ser356, by PAR-1/MARK stabilizes tau in the initial phase of mismetabolism, leading to subsequent phosphorylation events, accumulation, and toxicity. However, the relative contribution of phosphorylation at each of these sites to tau stabilization has not yet been elucidated. In a Drosophila model of human tau toxicity, we found that tau was phosphorylated at Ser262, but not at Ser356, and that blocking Ser262 phosphorylation decreased total tau levels. By contrast, when PAR-1 was co-overexpressed with tau, …

Probing The Nature Of Deficits In The ‘Approximate Number System’ In Children With Persistent Developmental Dyscalculia, S Bugden, Daniel Ansari

Brain and Mind Institute Researchers' Publications

In the present study we examined whether children with Developmental Dyscalculia (DD) exhibit a deficit in the so-called 'Approximate Number System' (ANS). To do so, we examined a group of elementary school children who demonstrated persistent low math achievement over 4 years and compared them to typically developing (TD), aged-matched controls. The integrity of the ANS was measured using the Panamath (www.panamath.org) non-symbolic numerical discrimination test. Children with DD demonstrated imprecise ANS acuity indexed by larger Weber fraction (w) compared to TD controls. Given recent findings showing that non-symbolic numerical discrimination is affected by visual parameters, we went further and …

A Quantitative Comparison Of The Hemispheric, Areal, And Laminar Origins Of Sensory And Motor Cortical Projections To The Superior Colliculus Of The Cat., Blake E Butler, Nicole Chabot, Stephen G Lomber

Brain and Mind Institute Researchers' Publications

The superior colliculus (SC) is a midbrain structure central to orienting behaviors. The organization of descending projections from sensory cortices to the SC has garnered much attention; however, rarely have projections from multiple modalities been quantified and contrasted, allowing for meaningful conclusions within a single species. Here, we examine corticotectal projections from visual, auditory, somatosensory, motor, and limbic cortices via retrograde pathway tracers injected throughout the superficial and deep layers of the cat SC. As anticipated, the majority of cortical inputs to the SC originate in the visual cortex. In fact, each field implicated in visual orienting behavior makes a …

Neural Control Of Tongue Movements Across Effort Levels, Megan Rovang, Angela M. Dietsch

UCARE Research Products

Background

A hallmark of Parkinson’s disease (PD) is a mismatch between the perceived effort and actual forces exerted during functional activities such as speech. Current evidence supports therapy to help reset this perception of effort, but the neurological underpinnings of such treatments are unclear. This study examined brain activity during tongue movements performed at varying levels of effort to determine (1) which brain areas are involved in each task, and (2) which areas, if any, scale in activation according to effort level. These results, considered with the neurological changes associated with PD, can be used to develop and refine treatment …

An Ultrasensitive Electrogenerated Chemiluminescence-Based Immunoassay For Specific Detection Of Zika Virus, Amber M. Paul, Dhiraj Acharya, Pradip Bastola, Linda Le, Estenfani Fernandez, Michael S. Diamond, Wujian Miao, Fengwei Bai

Publications

Zika virus (ZIKV) is a globally emerging mosquito-transmitted flavivirus that can cause severe fetal abnormalities, including microcephaly. As such, highly sensitive, specific, and cost-effective diagnostic methods are urgently needed. Here, we report a novel electrogenerated chemiluminescence (ECL)-based immunoassay for ultrasensitive and specific detection of ZIKV in human biological fluids. We loaded polystyrene beads (PSB) with a large number of ECL labels and conjugated them with anti-ZIKV monoclonal antibodies to generate anti-ZIKV-PSBs. These anti-ZIKV-PSBs efficiently captured ZIKV in solution forming ZIKV-anti-ZIKV-PSB complexes, which were subjected to measurement of ECL intensity after further magnetic beads separation. Our results show that the anti-ZIKV-PSBs …

Statistical Learning In Specific Language Impairment And Autism Spectrum Disorder: A Meta-Analysis, Rita Obeid, Patricia J. Brooks, Kasey L. Powers, Kristen Gillespie-Lynch, Jarrad A. G. Lum

Publications and Research

Impairments in statistical learning might be a common deficit among individuals with Specific Language Impairment (SLI) and Autism Spectrum Disorder (ASD). Using metaanalysis, we examined statistical learning in SLI (14 studies, 15 comparisons) and ASD (13 studies, 20 comparisons) to evaluate this hypothesis. Effect sizes were examined as a function of diagnosis across multiple statistical learning tasks (Serial Reaction Time, Contextual Cueing, Artificial Grammar Learning, Speech Stream, Observational Learning, and Probabilistic Classification). Individuals with SLI showed deficits in statistical learning relative to age-matched controls. In contrast, statistical learning was intact in individuals with ASD relative to controls. Effect sizes did …

Is Online Motor Control Really Impaired In Parkinson's Disease?, Kate E. Merritt

Electronic Thesis and Dissertation Repository

Patients with Parkinson’s disease (PD) are thought to be selectively impaired in consciously-mediated online automatic motor control, whereas the ability to perform subconscious online adjustments remains intact. This present study evaluates the hypothesis that the previously alleged deficits in online motor control in PD are not due to the consciousness of the correction, but rather are attributable to aspects of the prior experimental designs disproportionately penalizing patients for PD-related bradykinesia. Here, we implemented a modified traditional double-step paradigm to investigate consciously-mediated online motor control in PD, in a manner that would be unconfounded by disease-related bradykinesia. Further, we investigated the …

Microangiopathic Occlusion Of A Perforating Prepontine Long Circumferential Artery Presenting With Lower Motor Neuron Facial Weakness: Clinical And Radiological Correlation, Archie Defillo Md, Muhammad Shah Miran Md, Kenneth Shea Md, Michelle Peterson Np, Leah Roering Np, Jerone Kennedy Md, M. Fareed, K. Suri

Articles

Case Description: A 79-year old male patient with myelodysplastic syndrome associated with severe neutropenia, thrombocytopenia, anemia, hypertension, and hyperlipidemia was admitted for pneumonia secondary to influenza A. Two weeks later he presented with new symptoms of acute dysarthria, and left facial weakness involving his upper and lower face; the following day he developed left arm weakness. Admission computed tomography (CT) and MRI scans revealed an acute ischemic stroke (AIS) in the right posterior frontal cortex. The initial MRI was reported negative for pontine lesions. Anatomically, the cortical infarct could not explain his left lower motor neuron cranial nerve VII (LMN …

Closed-State Inactivation Involving An Internal Gate In Kv4.1 Channels Modulates Pore Blockade By Intracellular Quaternary Ammonium Ions., Jeffrey D. Fineberg, Tibor G. Szanto, Gyorgy Panyi, Manuel Covarrubias

Department of Neuroscience Faculty Papers

Voltage-gated K(+) (Kv) channel activation depends on interactions between voltage sensors and an intracellular activation gate that controls access to a central pore cavity. Here, we hypothesize that this gate is additionally responsible for closed-state inactivation (CSI) in Kv4.x channels. These Kv channels undergo CSI by a mechanism that is still poorly understood. To test the hypothesis, we deduced the state of the Kv4.1 channel intracellular gate by exploiting the trap-door paradigm of pore blockade by internally applied quaternary ammonium (QA) ions exhibiting slow blocking kinetics and high-affinity for a blocking site. We found that inactivation gating seemingly traps benzyl-tributylammonium …

Mechanical Reliability Of Implantable Polyimide-Based Magnetic Microactuators For Biofouling Removal, Christian G. Figueroa-Espada, Qi Yang, Hyowon Lee

The Summer Undergraduate Research Fellowship (SURF) Symposium

Hydrocephalus is a neurological disorder that typically requires a long-term implantation of a shunt system to manage its symptoms. These shunt systems are notorious for their extremely high failure rate. More than 40% of all implanted shunt systems fail within the first year of implantation. On average, 85% of all hydrocephalus patients with shunt systems undergo at least two shunt-revision surgeries within 10 years of implantation. A large portion of this high failure rate can be attributed to biofouling-related obstructions and infections. Previously, we developed flexible polyimide-based magnetic microactuators to remove obstructions formed on hydrocephalus shunts. To test the long-term …

A Trial-By-Trial Window Into Sensorimotor Transformations In The Human Motor Periphery., Chao Gu, Daniel K Wood, Paul L Gribble, Brian D Corneil

Brain and Mind Institute Researchers' Publications

UNLABELLED: The appearance of a novel visual stimulus generates a rapid stimulus-locked response (SLR) in the motor periphery within 100 ms of stimulus onset. Here, we recorded SLRs from an upper limb muscle while humans reached toward (pro-reach) or away (anti-reach) from a visual stimulus. The SLR on anti-reaches encoded the location of the visual stimulus rather than the movement goal. Further, SLR magnitude was attenuated when subjects reached away from rather than toward the visual stimulus. Remarkably, SLR magnitudes also correlated with reaction times on both pro-reaches and anti-reaches, but did so in opposite ways: larger SLRs preceded shorter …

Predominant Expression Of Alzheimer’S Disease-Associated Bin1 In Mature Oligodendrocytes And Localization To White Matter Tracts, Pierre De Rossi, Virginie Buggia-Prévot, Benjamin L. L. Clayton, Jared B. Vasquez, Carson Van Sanford, Robert J. Andrew, Ruben Lesnick, Alexandra Botté, Carole Deyts, Someya Salem, Eshaan Rao, Richard C. Rice, Angèle Parent, Satyabrata Kar, Brian Popko, Peter Pytel, Steven Estus, Gopal Thinakaran

Physiology Faculty Publications

Background: Genome-wide association studies have identified BIN1 within the second most significant susceptibility locus in late-onset Alzheimer’s disease (AD). BIN1 undergoes complex alternative splicing to generate multiple isoforms with diverse functions in multiple cellular processes including endocytosis and membrane remodeling. An increase in BIN1 expression in AD and an interaction between BIN1 and Tau have been reported. However, disparate descriptions of BIN1 expression and localization in the brain previously reported in the literature and the lack of clarity on brain BIN1 isoforms present formidable challenges to our understanding of how genetic variants in BIN1 increase the risk for AD.

Methods: …

Characterization And Personalization Of Botulinum Toxin Type A Therapy For Upper Limb Tremor In Parkinson Disease And Essential Tremor Patients Using Multi-Sensor Kinematic Technology, Olivia Samotus

Electronic Thesis and Dissertation Repository

Tremor commonly affects the upper extremities in essential tremor (ET) and Parkinson disease (PD) patients where many experience functional disability and ultimately seek therapy. As ET and PD tremor features overlap and clinical assessment is challenging due to its highly complex nature, misdiagnosis is common resulting in unsuitable therapies and prognosis. Current treatment options for ET and PD tremor include pharmacotherapy, focal therapy with botulinum toxin type A (BoNT-A) injections, and surgical interventions which provide modest relief of tremor. However, such therapies are commonly associated with significant adverse events and lack long-term efficacy and tolerability. Hence lack of standardized, objective …

Why Numerical Symbols Count In The Development Of Mathematical Skills: Evidence From Brain And Behaviour, Rebecca Merkley, Daniel Ansari

Brain and Mind Institute Researchers' Publications

Numerical skills measured prior to school entry are predictive of mathematics achievement longitudinally. It is therefore important that young children start school with strong mathematical foundations. Here we review evidence from behavior and neuroimaging that highlights numerical symbol knowledge as a key mediator between informal and formal mathematical competencies. We argue that future research should aim to elucidate cognitive and neuronal mechanisms underpinning the acquisition of symbolic knowledge. Furthermore, multiple aspects of numerical symbol knowledge, such as identification, cardinality, and ordinality, should be emphasized in preschool childcare environments

Multipronged Approach To Study Glaucoma-Associated Phenotypes, Sumana Rameshbabu Chintalapudi

Theses and Dissertations (ETD)

Glaucoma refers to a group of conditions characterized by death of RGCs, increase in intraocular pressure is usually a precursor to glaucoma and irreversible optic neuropathy leads to visual impairment and blindness. Recent advances have seen a surge of new ideas and technologies to aid in the early detection, efficacious treatments and neuroprotection. Despite advances we face several challenges in understanding the pathophysiology of glaucoma. One of the many challenges scientists and ophthalmologists are facing is, to better understand IOP, its role in glaucomatous damage and design safer, more predictable IOP-lowering therapies. Another challenge is to find a practical method …

Pituitary Adenylate-Cyclase Activating Polypeptide Regulates Hunger- And Palatability-Induced Binge Eating, Matthew M. Hurley, Brian Maunze, Megan E. Block, Michael J. Reilly, Eugene Kim, Yao Chen, Yan Li, David A. Baker, Qing-Song Liu, Sujean Choi

Biomedical Sciences Faculty Research and Publications

While pituitary adenylate cyclase activating polypeptide (PACAP) signaling in the hypothalamic ventromedial nuclei (VMN) has been shown to regulate feeding, a challenge in unmasking a role for this peptide in obesity is that excess feeding can involve numerous mechanisms including homeostatic (hunger) and hedonic-related (palatability) drives. In these studies, we first isolated distinct feeding drives by developing a novel model of binge behavior in which homeostatic-driven feeding was temporally separated from feeding driven by food palatability. We found that stimulation of the VMN, achieved by local microinjections of AMPA, decreased standard chow consumption in food-restricted rats (e.g., homeostatic feeding); surprisingly, …

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 …