Anatomy Commons^™

Glial Cytokine Modulation Improves Sleep And Circadian Disruption In Female Saa Knock-In Mice Of Alzheimer’S-Related Pathology, Teresa Macheda, Margaret R. Hawkins, Carrie E. Johnson, Madison G. Lapid, Haleigh R. Whitlock, Savannah M. Shepard, Makayla F. Cox, Kelly N. Roberts, Leke Bytyqi, Heather M. Hash, Omar A. Abou El-Ezz, Mohammed Abou El-Ezz, Katharina Kohler, Sridhar Sunderam, Bruce F. O'Hara, Linda J. Van Eldik, Michael Paul Murphy, Marilyn J. Duncan, Adam D. Bachstetter

Neuroscience Faculty Publications

Introduction: Sleep and circadian disturbances are early Alzheimer's disease (AD) features, yet mechanisms linking amyloid pathology, neuroinflammation, and sex differences remain unclear.

Methods: We longitudinally assessed sleep, circadian rhythms, and cognition in female and male hAPP^SAA knock-in and control mice from 2 to 19 months using piezoelectric monitoring. Aged mice (15 months) received MW151, a glial cytokine inhibitor (2.5 mg/kg, every other day, 6 weeks).

Results: Only females exhibited midlife reductions in light-phase sleep, increased rhythm fragmentation, and reduced rhythm stability, coinciding with selective reversal learning deficits, effects independent of amyloid or cytokine burden. MW151 increased light-phase sleep and …

Temporal Evolution Of Brain Inflammation In The Bilateral Common Carotid Artery Stenosis Model Of Chronic Cerebral Hypoperfusion, Makayla F. Cox, Jill M. Roberts, Ryan K. Shahidehpour, David L. Dornbos Iii, Adam D. Bachstetter

Neuroscience Faculty Publications

Chronic cerebral hypoperfusion is a major contributor to vascular cognitive impairment and dementia, primarily through its disruption of white matter integrity and promotion of neuroinflammatory cascades. The bilateral common carotid artery stenosis (BCAS) model has emerged as the predominant experimental approach for studying the effects of chronic cerebral hypoperfusion, particularly in aging-relevant contexts. This review synthesizes current knowledge of inflammatory responses in the BCAS model, with an emphasis on their temporal progression and functional consequences. We begin by outlining the clinical burden of hypoperfusion, the rationale for BCAS, and the hemodynamic phases it produces. We then examine early neurovascular unit …

Dim Light At Night Impacts Circadian Rhythms And Alzheimer’S Disease-Like Neuroinf Lammation And Neuropathology In Humanized App Saa Knock-In Mice, Marilyn J. Duncan, Margaret R. Hawkins, Leke Bytyqi, Haleigh R. Whitlock, Savannah M. Shepard, Makayla F. Cox, Esther G. Drinkard, Teresa Macheda, Kelly N. Roberts, Katharina Kohler, Mary-Claire Schmidt, Carrie E. Johnson, Sridhar Sunderam, Bruce F. O'Hara, Michael Paul Murphy, Adam D. Bachstetter

Neuroscience Faculty Publications

Artificial light at night (light pollution) is widespread but understudied in the context of Alzheimer’s disease (AD). Sleep and circadian disruption have been linked to amyloid-β (Aβ) accumulation and neuroinflammation, but whether dim light at night (dLAN) modifies these processes remains unclear. We tested whether chronic dLAN exposure (8 lux during the dark phase, 8 weeks) alters circadian rhythms, amyloid pathology, and neuroinflammation in 12–13 month-old humanized APP knock-in (KI) mice. hAPP^SAA KI mice, which develop plaques, were compared with hAPP^WT KI controls carrying only a humanized APP sequence. dLAN reduced circadian rhythm amplitude and stability while increasing …

Alzheimer’S Disease And The Immune System: The Emerging Role Of Temra Cells, Edric D. Winford, Adam D. Bachstetter

Neuroscience Faculty Publications

No abstract provided.

Age-Related Brain Atrophy And The Positive Effects Of Behavioral Enrichment In Middle-Aged Beagles., Jessica A Noche, Hamsanandini Radhakrishnan, Margo F. Ubele, Kathy Boaz, Jennifer L Mefford, Erin D Jones, Hollie Y Van Rooyen, Jessica A Perpich, Katie Mccarty, Beverly Meacham, Jeffrey R. Smiley, Stasia A Bembenek Bailey, László G Puskás, David K. Powell, Lorena Sordo, Michael J Phelan, Christopher M. Norris, Elizabeth Head, Craig E L Stark

Neuroscience Faculty Publications

Aging dogs serve as a valuable preclinical model for Alzheimer's disease (AD) due to their natural age-related development of β-amyloid (Aβ) plaques, human-like metabolism, and large brains that are ideal for studying structural brain aging trajectories from serial neuroimaging. Here we examined the effects of chronic treatment with the calcineurin inhibitor (CNI) tacrolimus or the nuclear factor of activated T cells (NFAT)-inhibiting compound Q134R on age-related canine brain atrophy from a longitudinal study in middle-aged beagles (36 females, 7 males) undergoing behavioral enrichment. Annual MRI was analyzed using modern, automated techniques for region-of-interest-based and voxel-based volumetric assessments. We found that …

An Efficient And High-Throughput Method For The Evaluation Of Mitochondrial Dysfunction In Frozen Brain Samples After Traumatic Brain Injury., Hemendra J Vekaria, Olivia J. Kalimon, Paresh Prajapati, Gopal V. Velmurugan, Patrick G Sullivan

Neuroscience Faculty Publications

Mitochondrial function analysis is a well-established method used in preclinical and clinical investigations to assess pathophysiological changes in various disease states, including traumatic brain injury (TBI). Although there are multiple approaches to assess mitochondrial function, one common method involves respirometric assays utilizing either Clark-type oxygen electrodes or fluorescent-based Seahorse analysis (Agilent). However, these functional analysis methods are typically limited to the availability of freshly isolated tissue samples due to the compromise of the electron transport chain (ETC) upon storage, caused by freeze-thaw-mediated breakdown of mitochondrial membranes. In this study, we propose and refine a method for evaluating electron flux through …

Association Of Plasma Neurofilament Light Chain With Microstructural White Matter Changes In Down Syndrome, Herminia Diana Rosas, Nathaniel David Mercaldo, Yasemin Hasimoglu, Melissa Petersen, Lydia R. Lewis, Florence Lai, David Powell, Asim Dhungana, Ali Demir, David Keater, Michael Yassa, Adam M. Brickman, Sid O'Bryant

Neuroscience Faculty Publications

INTRODUCTION: Both micro- and macrostructural white matter (WM) abnormalities, particularly those related to axonal degeneration, are associated with cognitive decline in adults with Down syndrome (DS) prior to a diagnosis of Alzheimer disease. Neurofilament light chain (NfL) is a support protein within myelinated axons released into blood following axonal damage. In this study we investigated cross-sectional relationships between WM microstructural changes as measured by diffusion tensor imaging (DTI) and plasma NfL concentration in adults with DS without dementia.

METHODS: Thirty cognitively stable (CS) adults with DS underwent diffusion-weighted MRI scanning and plasma NfL measurement. DTI measures of select WM tracts …

Microglia Proliferation Underlies Synaptic Dysfunction In The Prefrontal Cortex: Implications For The Pathogenesis Of Hiv-1- Associated Neurocognitive And Affective Alterations, Hailong Li, Kristen A. Mclaurin, Charles F. Mactutus, Rosemarie M. Booze

Neuroscience Faculty Publications

Microglia, which are productively infected by HIV-1, are critical for brain development and maturation, as well as synaptic plasticity. The pathophysiology of HIV-infected microglia and their role in the pathogenesis of HIV-1-associated neurocognitive and affective alterations, however, remains understudied. Three complementary aims were undertaken to critically address this knowledge gap. First, the expression of HIV-1 mRNA in the dorsolateral prefrontal cortex of postmortem HIV-1 seropositive individuals with HAND was investigated. Utilization of a combined RNAscope multiplex fluorescent and immunostaining assay revealed prominent HIV-1 mRNA in microglia of postmortem HIV-1 seropositive individuals with HAND. Second, measures of microglia proliferation and neuronal …

What Lies Beneath? Molecular Evolution During The Radiation Of Caecilian Amphibians, María Torres-Sánchez, David J. Gower, David Alvarez-Ponce, Christopher J. Creevey, Mark Wilkinson, Diego San Mauro

Neuroscience Faculty Publications

Background: Evolution leaves an imprint in species through genetic change. At the molecular level, evolutionary changes can be explored by studying ratios of nucleotide substitutions. The interplay among molecular evolution, derived phenotypes, and ecological ranges can provide insights into adaptive radiations. Caecilians (order Gymnophiona), probably the least known of the major lineages of vertebrates, are limbless tropical amphibians, with adults of most species burrowing in soils (fossoriality). This enigmatic order of amphibians are very distinct phenotypically from other extant amphibians and likely from the ancestor of Lissamphibia, but little to nothing is known about the molecular changes underpinning their radiation. …

Hdac Regulates Transcription At The Outset Of Axolotl Tail Regeneration, S. Randal Voss, Larissa V. Ponomareva, Varun B. Dwaraka, Kaitlin E. Pardue, Nour W. Al Haj Baddar, A. Katherine Rodgers, M. Ryan Woodcock, Qingchao Qiu, Anne Crowner, Dana Blichmann, Shivam Khatri, Jon S. Thorson

Neuroscience Faculty Publications

Tissue regeneration is associated with complex changes in gene expression and post-translational modifications of proteins, including transcription factors and histones that comprise chromatin. We tested 172 compounds designed to target epigenetic mechanisms in an axolotl (Ambystoma mexicanum) embryo tail regeneration assay. A relatively large number of compounds (N = 55) inhibited tail regeneration, including 18 histone deacetylase inhibitors (HDACi). In particular, romidepsin, an FDA-approved anticancer drug, potently inhibited tail regeneration when embryos were treated continuously for 7 days. Additional experiments revealed that romidepsin acted within a very narrow, post-injury window. Romidepsin treatment for only 1-minute post amputation inhibited …

Rediscovering The Axolotl As A Model For Thyroid Hormone Dependent Development, Anne Crowner, Shivam Khatri, Dana Blichmann, S. Randal Voss

Neuroscience Faculty Publications

The Mexican axolotl (Ambystoma mexicanum) is an important model organism in biomedical research. Much current attention is focused on the axolotl's amazing ability to regenerate tissues and whole organs after injury. However, not forgotten is the axolotl's equally amazing ability to thwart aspects of tissue maturation and retain juvenile morphology into the adult phase of life. Unlike close tiger salamander relatives that undergo a thyroid hormone regulated metamorphosis, the axolotl does not typically undergo a metamorphosis. Instead, the axolotl exhibits a paedomorphic mode of development that enables a completely aquatic life cycle. The evolution of paedomorphosis allowed axolotls …

The Effects Of Huntingtin-Lowering: What Do We Know So Far?, William F. Kaemmerer, Richard C. Grondin

Neuroscience Faculty Publications

Therapies targeting mutant huntingtin DNA, mRNA, and protein have a chance at becoming the first disease-modifying treatments for Huntington’s disease, a fatal inherited neurodegenerative disorder for which only symptom management treatments are available today. This review focuses on evidence addressing several key questions pertinent to huntingtin-lowering, ranging from the functions of wild-type huntingtin (wtHTT) that may be disrupted by huntingtin-lowering treatments through the various ways huntingtin can be lowered, the tolerability of wtHTT-lowering in mice and primates, what has been found in the Ionis Pharmaceutical safety trial of a huntingtin-lowering therapy, and to the question of how much mutant huntingtin …

Validations Of Apomorphine-Induced Bold Activation Correlations In Hemiparkinsonian Rhesus Macaques, Jorge E. Quintero, Yi Ai, Anders H. Andersen, Peter A. Hardy, Richard Grondin, Zain Guduru, Don M. Gash, Greg A. Gerhardt, Zhiming Zhang

Neuroscience Faculty Publications

Identification of Parkinson's disease at the earliest possible stage of the disease may provide the best opportunity for the use of disease modifying treatments. However, diagnosing the disease during the pre-symptomatic period remains an unmet goal. To that end, we used pharmacological MRI (phMRI) to assess the function of the cortico-basal ganglia circuit in a non-human primate model of dopamine deficiency to determine the possible relationships between phMRI signals with behavioral, neurochemical, and histological measurements. Animals with unilateral treatments with the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), that expressed stable, long-term hemiparkinsonism were challenged with the dopaminergic receptor agonist, apomorphine, and structure-specific phMRI …

Transcriptional Correlates Of Proximal-Distal Identify And Regeneration Timing In Axolotl Limbs, S. Randal Voss, David Murrugarra, Tyler B. Jensen, James R Monaghan

Neuroscience Faculty Publications

Cells within salamander limbs retain memories that inform the correct replacement of amputated tissues at different positions along the length of the arm, with proximal and distal amputations completing regeneration at similar times. We investigated the possibility that positional memory is associated with variation in transcript abundances along the proximal-distal limb axis. Transcripts were deeply sampled from Ambystoma mexicanum limbs at the time they were administered fore arm vs upper arm amputations, and at 19 post-amputation time points. After amputation and prior to regenerative outgrowth, genes typically expressed by differentiated muscle cells declined more rapidly in upper arms while cell …

Adaptation Of Microelectrode Array Technology For The Study Of Anesthesia-Induced Neurotoxicity In The Intact Piglet Brain, Emily D. Geyer, Prithvi A. Shetty, Christopher J. Suozzi, David Z. Allen, Pamela P. Benavidez, Joseph Liu, Charles N. Hollis, Greg A. Gerhardt, Jorge E. Quintero, Jason J. Burmeister, Emmett E. Whitaker

Neuroscience Faculty Publications

Every year, millions of children undergo anesthesia for a multitude of procedures. However, studies in both animals and humans have called into question the safety of anesthesia in children, implicating anesthetics as potentially toxic to the brain in development. To date, no studies have successfully elucidated the mechanism(s) by which anesthesia may be neurotoxic. Animal studies allow investigation of such mechanisms, and neonatal piglets represent an excellent model to study these effects due to their striking developmental similarities to the human brain.

This protocol adapts the use of enzyme-based microelectrode array (MEA) technology as a novel way to study the …

Bilateral Carotid Artery Stenosis Causes Unexpected Early Changes In Brain Extracellular Matrix And Blood-Brain Barrier Integrity In Mice, Jill M. Roberts, Michael E. Maniskas, Gregory J. Bix

Neuroscience Faculty Publications

Bilateral carotid artery stenosis (BCAS) is one experimental model of vascular dementia thought to preferentially impact brain white matter. Indeed, few studies report hippocampal and cortical pathology prior to 30 days post-stenosis; though it is unclear whether those studies examined regions outside the white matter. Since changes in the blood-brain barrier (BBB) permeability precede more overt brain pathology in various diseases, we hypothesized that changes within the BBB and/or BBB-associated extracellular matrix (ECM) could occur earlier after BCAS in the hippocampus, cortex and striatum and be a precursor of longer term pathology. Here, C57Bl/6 mice underwent BCAS or sham surgeries …

Amperometric Self-Referencing Ceramic Based Microelectrode Arrays For D-Serine Detection, Diana Campos-Beltrán, Åsa Konradsson-Geuken, Jorge E. Quintero, Lisa Marshall

Neuroscience Faculty Publications

D-serine is the major D-amino acid in the mammalian central nervous system. As the dominant co-agonist of the endogenous synaptic NMDA receptor, D-serine plays a role in synaptic plasticity, learning, and memory. Alterations in D-serine are linked to neuropsychiatric disorders including schizophrenia. Thus, it is of increasing interest to monitor the concentration of D-serine in vivo as a relevant player in dynamic neuron-glia network activity. Here we present a procedure for amperometric detection of D-serine with self-referencing ceramic-based microelectrode arrays (MEAs) coated with D-amino acid oxidase from the yeast Rhodotorula gracilis (RgDAAO). We demonstrate in vitro D-serine recordings with a …

Ginsenoside Re Protects Methamphetamine-Induced Dopaminergic Neurotoxicity In Mice Via Upregulation Of Dynorphin-Mediated Κ-Opioid Receptor And Downregulation Of Substance P-Mediated Neurokinin 1 Receptor, Duy-Khanh Dang, Eun-Joo Shin, Dae-Joong Kim, Hai-Quyen Tran, Ji Hoon Jeong, Choon-Gon Jang, Seung-Yeol Nah, Jung Hwan Jeong, Jae Kyung Byun, Sung Kwon Ko, Guoying Bing, Jau-Shyong Hong, Hyoung-Chun Kim

Neuroscience Faculty Publications

Background: We previously reported that ginsenoside Re (GRe) attenuated against methamphetamine (MA)-induced neurotoxicity via anti-inflammatory and antioxidant potentials. We also demonstrated that dynorphin possesses anti-inflammatory and antioxidant potentials against dopaminergic loss, and that balance between dynorphin and substance P is important for dopaminergic neuroprotection. Thus, we examined whether GRe positively affects interactive modulation between dynorphin and substance P against MA neurotoxicity in mice.

Methods: We examined changes in dynorphin peptide level, prodynorphin mRNA, and substance P mRNA, substance P-immunoreactivity, homeostasis in enzymatic antioxidant system, oxidative parameter, microglial activation, and pro-apoptotic parameter after a neurotoxic dose of MA to clarify the …

Age- And Sex-Related Changes In Fasting Plasma Glucose And Lipoprotein In Cynomolgus Monkeys, Feng Yue, Guodong Zhang, Rongping Tang, Zhouquan Zhang, Liqiong Teng, Zhiming Zhang

Neuroscience Faculty Publications

Background: The age-related dysfunction of glucose and lipid metabolism has a long-standing relationship with cardiovascular and neurodegenerative disease. However, the effects of metabolic dysfunction on men and women are different. Reasons for these sex differences remains unclear. Cynomolgus monkeys have been used, in the past, for the study of human metabolic diseases due to their biologically proximity to humans. Nevertheless, few studies to date have focused on both age- and sex-related differences in glucose and lipid metabolism. The present study was designed to specifically address these questions by using a large cohort of cynomolgus monkeys (N = 1,399) including …

Proceedings Of The Third Annual Deep Brain Stimulation Think Tank: A Review Of Emerging Issues And Technologies, P. Justin Rossi, Aysegul Gunduz, Jack Judy, Linda Wilson, Andre Machado, James J Giordano, W. Jeff Elias, Marvin A. Rossi, Christopher L. Butson, Michael D. Fox, Cameron C. Mcintyre, Nader Pouratian, Nicole C. Swann, Coralie De Hemptinne, Robert E. Gross, Howard J. Chizeck, Michele Tagliati, Andres M. Lozano, Wayne Goodman, Jean-Philippe Langevin, Ron L. Alterman, Umer Akbar, Greg A. Gerhardt, Warren M. Grill, Mark Hallett, Todd Herrington, Jeffrey Herron, Craig Van Horne, Brian H. Kopell, Anthony E. Lang

Neuroscience Faculty Publications

The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and …

Dopaminergic Modulation Of Medial Prefrontal Cortex Deactivation In Parkinson Depression, Anders H. Andersen, Charles D. Smith, John T. Slevin, Richard J. Kryscio, Catherine A. Martin, Frederick A. Schmitt, Lee X. Blonder

Neuroscience Faculty Publications

Parkinson's disease (PD) is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD) patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD) patients. Participants included 18 ndPD patients (11 men, 7 women) and 10 dPD patients (7 men, 3 women). Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after …

White Matter Microstructure Contributes To Age-Related Declines In Task-Induced Deactivation Of The Default Mode Network, Christopher A. Brown, Jonathan G. Hakun, Zude Zhu, Nathan F. Johnson, Brian T. Gold

Neuroscience Faculty Publications

Task-induced deactivations within the brain’s default mode network (DMN) are thought to reflect suppression of endogenous thought processes to support exogenous goal-directed task processes. Older adults are known to show reductions in deactivation of the DMN compared to younger adults. However, little is understood about the mechanisms contributing to functional dysregulation of the DMN in aging. Here, we explored the relationships between functional modulation of the DMN and age, task performance and white matter (WM) microstructure. Participants were 117 adults ranging from 25 to 83 years old who completed an fMRI task switching paradigm, including easy (single) and difficult (mixed) …

The Hand Of Homo Naledi, Tracy L. Kivell, Andrew S. Deane, Matthew W. Tocheri, Caley M. Orr, Peter Schmid, John Hawks, Lee R. Berger, Steven E. Churchill

Neuroscience Faculty Publications

A nearly complete right hand of an adult hominin was recovered from the Rising Star cave system, South Africa. Based on associated hominin material, the bones of this hand are attributed to Homo naledi. This hand reveals a long, robust thumb and derived wrist morphology that is shared with Neandertals and modern humans, and considered adaptive for intensified manual manipulation. However, the finger bones are longer and more curved than in most australopiths, indicating frequent use of the hand during life for strong grasping during locomotor climbing and suspension. These markedly curved digits in combination with an otherwise human-like …

Distributed Encoding Of Spatial And Object Categories In Primate Hippocampal Microcircuits, Ioan Opris, Lucas M. Santos, Greg A. Gerhardt, Dong Song, Theodore W. Berger, Robert E. Hampson, Sam A. Deadwyler

Neuroscience Faculty Publications

The primate hippocampus plays critical roles in the encoding, representation, categorization and retrieval of cognitive information. Such cognitive abilities may use the transformational input-output properties of hippocampal laminar microcircuitry to generate spatial representations and to categorize features of objects, images, and their numeric characteristics. Four nonhuman primates were trained in a delayed-match-to-sample (DMS) task while multi-neuron activity was simultaneously recorded from the CA1 and CA3 hippocampal cell fields. The results show differential encoding of spatial location and categorization of images presented as relevant stimuli in the task. Individual hippocampal cells encoded visual stimuli only on specific types of trials in …

The Foot Of Homo Naledi, W. E. H. Harcourt-Smith, Z. Throckmorton, K. A. Congdon, B. Zipfel, Andrew S. Deane, M. S. M. Drapeau, S. E. Churchill, L. R. Berger, J. M. Desilva

Neuroscience Faculty Publications

Modern humans are characterized by a highly specialized foot that reflects our obligate bipedalism. Our understanding of hominin foot evolution is, although, hindered by a paucity of well-associated remains. Here we describe the foot of Homo naledi from Dinaledi Chamber, South Africa, using 107 pedal elements, including one nearly-complete adult foot. The H. naledi foot is predominantly modern human-like in morphology and inferred function, with an adducted hallux, an elongated tarsus, and derived ankle and calcaneocuboid joints. In combination, these features indicate a foot well adapted for striding bipedalism. However, the H. naledi foot differs from modern humans in having …

Homo Naledi, A New Species Of The Genus Homo From The Dinaledi Chamber, South Africa, Lee R. Berger, John Hawks, Darryl J. De Ruiter, Steven E. Churchill, Peter Schmid, Lucas K. Delezene, Tracy L. Kivell, Heather M. Garvin, Scott A. Williams, Jeremy M. Desilva, Matthew M. Skinner, Charles M. Musiba, Noel Cameron, Trenton W. Holliday, William Harcourt-Smith, Rebecca R. Ackermann, Markus Bastir, Barry Bogin, Debra Bolter, Juliet Brophy, Zachary D. Cofran, Kimberly A. Congdon, Andrew S. Deane, Mana Dembo, Michelle Drapeau, Marina C. Elliott, Elen M. Feuerriegel, Daniel Garcia-Martinez, David J. Green, Alia Gurtov, Joel D. Irish, Ashley Kruger, Myra F. Laird, Damiano Marchi, Marc R. Meyer, Shahed Nalla, Enquye W. Negash, Caley M. Orr, Davorka Radovcic, Lauren Schroeder, Jill E. Scott, Zachary Throckmorton, Matthew W. Tocheri, Caroline Vansickle, Christopher S. Walker, Pianpian Wei, Bernhard Zipfel

Neuroscience Faculty Publications

Homo naledi is a previously-unknown species of extinct hominin discovered within the Dinaledi Chamber of the Rising Star cave system, Cradle of Humankind, South Africa. This species is characterized by body mass and stature similar to small-bodied human populations but a small endocranial volume similar to australopiths. Cranial morphology of H. naledi is unique, but most similar to early Homo species including Homo erectus, Homo habilis or Homo rudolfensis. While primitive, the dentition is generally small and simple in occlusal morphology. H. naledi has humanlike manipulatory adaptations of the hand and wrist. It also exhibits a humanlike foot …

Onset Time And Durability Of Huntingtin Suppression In Rhesus Putamen After Direct Infusion Of Antihuntingtin Sirna, Richard Grondin, Pei Ge, Qingmin Chen, Jessica E. Sutherland, Zhiming Zhang, Don M. Gash, David K. Stiles, Gregory R. Stewart, Dinah W. Y. Sah, William F. Kaemmerer

Neuroscience Faculty Publications

One possible treatment for Huntington's disease involves direct infusion of a small, interfering RNA (siRNA) designed to reduce huntingtin expression into brain tissue from a chronically implanted programmable pump. Here, we studied the suppression of huntingtin mRNA achievable with short infusion times, and investigated how long suppression may persist after infusion ceases. Rhesus monkeys received 3 days of infusion of Magnevist into the putamen to confirm catheter patency and fluid distribution. After a 1-week washout period, monkeys received radiolabeled siRNA targeting huntingtin. After 1 or 3 days of siRNA delivery, monkeys were either terminated, or their pumps were shut off …

Neuron-Based Heredity And Human Evolution, Don M. Gash, Andrew S. Deane

Neuroscience Faculty Publications

It is widely recognized that human evolution has been driven by two systems of heredity: one DNA-based and the other based on the transmission of behaviorally acquired information via nervous system functions. The genetic system is ancient, going back to the appearance of life on Earth. It is responsible for the evolutionary processes described by Darwin. By comparison, the nervous system is relatively newly minted and in its highest form, responsible for ideation and mind-to-mind transmission of information. Here the informational capabilities and functions of the two systems are compared. While employing quite different mechanisms for encoding, storing and transmission …

Disruption Of Columnar And Laminar Cognitive Processing In Primate Prefrontal Cortex Following Cocaine Exposure, Ioan Opris, Greg A. Gerhardt, Robert E. Hampson, Sam A. Deadwyler

Neuroscience Faculty Publications

Prefrontal cortical activity in primate brain plays a critical role in cognitive processes involving working memory and the executive control of behavior. Groups of prefrontal cortical neurons within specified cortical layers along cortical minicolumns differentially generate inter- and intra-laminar firing to process relevant information for goal oriented behavior. However, it is not yet understood how cocaine modulates such differential firing in prefrontal cortical layers. Rhesus macaque nonhuman primates (NHPs) were trained in a visual delayed match-to-sample (DMS) task while the activity of prefrontal cortical neurons (areas 46, 8 and 6) was recorded simultaneously with a custom multielectrode array in cell …

Designer Receptors Enhance Memory In A Mouse Model Of Down Syndrome, Ashley M. Fortress, Eric D. Hamlett, Elena M. Vazey, Gary Aston-Jones, Wayne A. Cass, Heather A. Boger, Ann-Charlotte E. Granholm

Neuroscience Faculty Publications

Designer receptors exclusively activated by designer drugs (DREADDs) are novel and powerful tools to investigate discrete neuronal populations in the brain. We have used DREADDs to stimulate degenerating neurons in a Down syndrome (DS) model, Ts65Dn mice. Individuals with DS develop Alzheimer's disease (AD) neuropathology and have elevated risk for dementia starting in their 30s and 40s. Individuals with DS often exhibit working memory deficits coupled with degeneration of the locus coeruleus (LC) norepinephrine (NE) neurons. It is thought that LC degeneration precedes other AD-related neuronal loss, and LC noradrenergic integrity is important for executive function, working memory, and attention. …