Neuroscience and Neurobiology Commons^™

Apoe Stabilization By Exercise Prevents Aging Neurovascular Dysfunction And Complement Induction, Ileana Soto Reyes, Leah C. Graham, Hannah J. Richter, Stephen N. Simeone, Jake E. Radell, Weronika Grabowska, W. Keith Funkhouser, Megan C. Howell, Gareth R. Howell

College of Science & Mathematics Departmental Research

Aging is the major risk factor for neurodegenerative diseases such as Alzheimer's disease, but little is known about the processes that lead to age-related decline of brain structures and function. Here we use RNA-seq in combination with high resolution histological analyses to show that aging leads to a significant deterioration of neurovascular structures including basement membrane reduction, pericyte loss, and astrocyte dysfunction. Neurovascular decline was sufficient to cause vascular leakage and correlated strongly with an increase in neuroinflammation including up-regulation of complement component C1QA in microglia/monocytes. Importantly, long-term aerobic exercise from midlife to old age prevented this age-related neurovascular decline, …

Age-Related Sexual Dimorphism In Temporal Discrimination And In Adult-Onset Dystonia Suggests Gabaergic Mechanisms, John Butler, Ines M. Beiser, Laura Williams, Eavan Mcgovern, Fiona Molloy, Timothy Lynch, Dan G. Healy, Helena Moore, Richard Walsh, Richard B. Reilly, Sean O'Riordan, Cathal Walsh, Michael Hutchinson

Articles

Background: Adult-onset isolated focal dystonia (AOIFD) presenting in early adult life is more frequent in men, whereas in middle age it is female predominant. Temporal discrimination, an endophenotype of adult-onset idiopathic isolated focal dystonia, shows evidence of sexual dimorphism in healthy participants. Objectives: We assessed the distinctive features of age-related sexual dimorphism of (i) sex ratios in dystonia phenotypes and (ii) sexual dimorphism in temporal discrimination in unaffected relatives of cervical dystonia patients. Methods: We performed (i) a meta-regression analysis of the proportion of men in published cohorts of phenotypes of adult-onset dystonia in relation to their mean age of …

Involvement Of The Right Hemisphere In Reading Comprehension: A Dti Study, Tzipi Horowitz-Kraus, Yingying Wang, Elena Plante, Scott K. Holland

Center for Brain, Biology, and Behavior: Faculty Publications

The Simple View of reading emphasizes the critical role of two factors in normal reading skills: word recognition and reading comprehension. The current study aims to identify the anatomical support for aspects of reading performance that fall within these two components. Fractional anisotropy (FA) values were obtained from Diffusion Tensor images in twenty-one typical adolescents and young adults using the Tract Based Spatial Statistics (TBSS) method. We focused on the Arcuate Fasciculus (AF) and Inferior Longitudinal Fasciculus (ILF) as fiber tracts that connect regions already implicated in the distributed cortical network for reading. Our results demonstrate dissociation between word-level and …

The Neurochemistry And Social Flow Of Singing: Bonding And Oxytocin, Jason R. Keeler, Brittany L. Neuser, John M. Spitsbergen, Daniel J.M. Waters, John-Mary Vianney

BRAIN Lab Research

Music is used in healthcare to promote physical and psychological well-being. As clinical applications of music continue to expand, there is a growing need to understand the biological mechanisms by which music influences health. Here we explore the neurochemistry and social flow of group singing. Four participants from a vocal jazz ensemble were conveniently sampled to sing together in two separate performances: pre-composed and improvised. Concentrations of plasmaoxytocin and adrenocorticotropichormone (ACTH) were measured before and after each singing condition to assess levels of social affiliation, engagement and arousal. Avalidated assessment off low state was administered after each singing condition to …

Isoflurane Inhibits Synaptic Vesicle Exocytosis Through Reduced Ca2+ Influx, Not Ca2+-Exocytosis Coupling, Joel Baumgart, Zhen-Yu Zhou, Masato Hara, Daniel Cook, Michael Hoppa

Dartmouth Scholarship

Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits synaptic vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition of presynaptic Ca2+ influx without significantly altering the Ca2+ sensitivity of SV exocytosis. A clinically relevant concentration of isoflurane (0.7 mM) inhibited changes in [Ca2+]i driven by single action potentials (APs) by 25 ± 3%, which in turn led to 62 ± 3% inhibition of single AP-triggered exocytosis at 4 mM extracellular Ca2+ ([Ca2+]e). Lowering external Ca2+ to match the isoflurane-induced reduction in …

Characterizing The Rogfp2-Orp1 Fluorescent Biosensor For Detecting Oxidative Stress In Mammalian Cells, Sara A. Doan, Stevie Norcross, Mathew Tantama

The Summer Undergraduate Research Fellowship (SURF) Symposium

Parkinson’s disease is a neurodegenerative disease involving the death of neurons in the substantia nigra and loss of the neurotransmitter, dopamine. The disease leads to progressive loss of motor control. Exact causes and mechanisms by which Parkinson’s disease proceeds are unknown, however, previous experiments determine oxidative stress in mitochondria as a factor that results in cell death. Strategies have been implemented to generate fluorescent biosensors to monitor reactive oxygen species (ROS) concentrations while simultaneously measuring the spatiotemporal distribution and correlation between the ROS, cellular function and organelle. Orp1, an enzyme found in yeast, is a sensitive oxidizing species and when …

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 …

Neurobiology Of Seasonal Life-History Transitions, Ashley Rae Lucas

Dissertations and Theses

Many animals exhibit seasonal changes in life-history stages, and these seasonal transitions are often accompanied by dramatic switches in behavior. While the neuroendocrine mechanisms that regulate such behavioral transitions are poorly understood, arginine vasotocin (AVT) and neuropeptide Y (NPY) are excellent candidates because they regulate reproductive and feeding behavior, respectively. In this study, I asked if seasonal changes in AVT and/or NPY are concomitant with spring migration away from the breeding grounds, as male and female red-sided garter snakes (Thamnophis sirtalis parietalis) are transitioning from reproductive to non-reproductive behavior during this time. To address this question, I collected …

Effects Of Testosterone On The Spatial Ecology, Coloration, And Brain Regions In Western Fence Lizards, Sceloporus Occidentalis, Rachel Catharine Wilson

Master's Theses

An organism’s spatial ecology allows for access to essential resources such as food, mates, and escape from predators. Home range size, or the total area an organism inhabits, varies in relation to numerous factors including seasonality. During the breeding season, home range size increases in males across taxa. In addition, males usually also have larger home range sizes than females. This implicates testosterone (T) as a possible mediator of this relationship. Indeed, T causes an increase in home range size of males in numerous species of lizards. In addition to T causing an increase in home range size, it also …

Familiar Face Detection In 180ms, Matteo Visconti Di Oleggio Castello, M. Ida Gobbini

Dartmouth Scholarship

The visual system is tuned for rapid detection of faces, with the fastest choice saccade to a face at 100ms. Familiar faces have a more robust representation than do unfamiliar faces, and are detected faster in the absence of awareness and with reduced attentional resources. Faces of family and close friends become familiar over a protracted period involving learning the unique visual appearance, including a view-invariant representation, as well as person knowledge. We investigated the effect of personal familiarity on the earliest stages of face processing by using a saccadic-choice task to measure how fast familiar face detection can happen. …

Short-Term Memory For Space And Time Flexibly Recruit Complementary Sensory-Biased Frontal Lobe Attention Networks, Samantha W. Michalka, Lingqiang Kong, Maya L. Rosen, Barbara G. Shinn-Cunningham, David C. Somers

Neuroscience: Faculty Publications

The frontal lobes control wide-ranging cognitive functions; however, functional subdivisions of human frontal cortex are only coarsely mapped. Here, functional magnetic resonance imaging reveals two distinct visual-biased attention regions in lateral frontal cortex, superior precentral sulcus (sPCS) and inferior precentral sulcus (iPCS), anatomically interdigitated with two auditory-biased attention regions, transverse gyrus intersecting precentral sulcus (tgPCS) and caudal inferior frontal sulcus (cIFS). Intrinsic functional connectivity analysis demonstrates that sPCS and iPCS fall within a broad visual-attention network, while tgPCS and cIFS fall within a broad auditory-attention network. Interestingly, we observe that spatial and temporal short-term memory (STM), respectively, recruit visual and …

Characteristics Of Exocytosis And Endocytosis In Photoreceptors, Karlene M. Cork

Theses & Dissertations

Photoreceptors signal changes in light intensity to downstream retinal neurons through the exocytosis of glutamate-containing synaptic vesicles. The maintenance of the vesicle exocytosis and endocytosis process is essential for ongoing synaptic signaling. This study investigated the properties of exocytosis and endocytosis in photoreceptors and their role in ongoing neurotransmission.

I used electrophysiology and imaging techniques to study the properties of vesicle exocytosis and endocytosis in photoreceptors. First, we examined baseline release in photoreceptors that occurs in the absence of depolarizing stimulation. We measured mEPSCs in whole cell patch clamp recordings from horizontal cells. After inhibiting Ca²⁺ influx and efflux …

Effects Of Maternal Immune Activation And Repeated Maternal Separation On Postpartum Behaviors In The Female Rat Offspring, Shinnyi Chou

Theses & Dissertations

Early life stress can induce persistent brain and behavioral alterations. As a lifetime history of clinical symptoms similar to those caused by early adversities may predict postpartum dysfunctions, these stressors likely contribute to their etiology. Postpartum neuropsychiatric disorders (e.g. postpartum depression, anxiety and depression) are costly, yet due to the complex neuronal reorganization during this period, insights into how early adversities-induced CNS functional changes affect postpartum processes remain limited, especially under multiple stressors. Thus, there is a need to determine postpartum functions altered by early stress, in order to increase understandings of risks associated with postpartum maladaptations. Accordingly, this work …

Influences Of Long-Term Memory-Guided Attention And Stimulus-Guided Attention On Visuospatial Representations Within Human Intraparietal Sulcus, Maya L. Rosen, Chantal E. Stern, Samantha W. Michalka, Kathryn J. Devaney, David C. Somers

Neuroscience: Faculty Publications

Human parietal cortex plays a central role in encoding visuospatial information and multiple visual maps exist within the intraparietalsulcus (IPS), with each hemisphere symmetrically representing contralateral visual space. Two forms of hemispheric asymmetries havebeen identified in parietal cortex ventrolateral to visuotopic IPS. Key attentional processes are localized to right lateral parietal cortex inthe temporoparietal junction and long-term memory (LTM) retrieval processes are localized to the left lateral parietal cortex in theangular gyrus. Here, using fMRI, we investigate how spatial representations of visuotopic IPS are influenced by stimulus-guided visuospatialattention and by LTM-guided visuospatial attention. We replicate prior findings that a hemispheric …

A Screen To Identify Saga-Activated Genes That Are Required For Proper Photoreceptor Axon Targeting In Drosophila Melanogaster, Kaelan J. Brennan, Vikki M. Weake, Jingqun Q. Ma

The Summer Undergraduate Research Fellowship (SURF) Symposium

The inherited human genetic disease spinocerebellar ataxia type 7 (SCA7) is characterized by progressive neurodegeneration and visual impairment that ultimately leads to blindness. SCA7 results from a mutation in the human ATXN7 gene that causes an expansion of polyglutamine tracts in this gene’s corresponding protein. Human ATXN7 protein serves as a component of the deubiquitylase (DUB) module of the large, multi-subunit complex Spt-Ada-Gcn acetyltransferase, or SAGA. SAGA is a transcriptional coactivator and histone modifier that functions to deubiquitylate histone H2B and allow for transcription of SAGA-mediated genes to occur. In Drosophila, mutations in SAGA DUB’s Nonstop and sgf11 components …

Analysis Of Mitochondrial Turnover In Neuromuscular Junctions Of Parkin Mutants, Kenny Nguyen, Hyun Sung, Peter J. Hollenbeck

The Summer Undergraduate Research Fellowship (SURF) Symposium

The accumulation of dysfunctional or damaged mitochondria in neurons has been linked to the pathogenesis of many neurodegenerative diseases, such as Parkinson’s disease. It has been proposed that proteins PINK1 and Parkin regulate mitochondrial quality control by selectively targeting depolarized mitochondria for autophagic degradation, a process known as mitophagy. Though previously analyzed in the cell bodies and axons of neurons, the role of the PINK1/Parkin pathway in the synapse is unclear, and it is not known whether mitochondrial turnover occurs in the neuromuscular junctions (NMJs). To study this, intact Drosophila nervous systems were analyzed in vivo by performing gentle dissections …

Competitive Tuning Of Calmodulin Target Protein Activation Drives E-Ltp Induction In Ca1 Hippocampal Neurons, Daniel R. Romano, Tamara L. Kinzer-Ursem

The Summer Undergraduate Research Fellowship (SURF) Symposium

A number of neurological disorders are caused by disruptions in dynamic neuronal connections called synapses. Normally, electrical activity between neurons activates protein cascades that cause long-lasting, localized changes in the structure and molecular composition of synapses. These changes either increase or decrease the strength of synaptic connections, leading to long-term-potentiation (LTP) or long-term-depression (LTD), respectively. The protein cascades responsible for this synaptic plasticity are initiated in a stimulus-dependent manner by the Ca²⁺ sensor calmodulin (CaM). Ultimately, it is disruptions within these signaling pathways that cause disease. Traditionally, these protein networks are studied in the laboratory, but limitations in existing …

Behavioral Outputs Of Fragile-X Autistic Mice Exposed To Open-Field, Randomized, Short-Term Visual Stimuli, Nicholas M. Dicola, Alexander A. Chubykin

The Summer Undergraduate Research Fellowship (SURF) Symposium

Animal models of different neurological disorders are required for studying the pathophysiology of these diseases, and for potential development of pharmacological and behavioral treatments. The scientific community often uses mouse models for behavior studies due to their powerful genetic tools and low cost. However, subjective measurement techniques are often used when analyzing mice for behavioral traits which often results in discrepancies in results. An automated tracking software would aim to eliminate these discrepancies and subjective analysis. This lab has developed a software program which offered an ability to automatically collect open-field behavioral data with simultaneous on-line analysis. Python, an open …

Hippocalcin Response To Calcium: Do Conserved Tryptophans – W30 Or W103 – Matter?, Sunkesula K. Sagar

Graduate School of Biomedical Sciences Theses and Dissertations

Changes in intracellular calcium levels play a very important role in cell signaling, in turn, affecting neuronal functions such as memory, learning and cell death. A class of proteins called Neuronal Calcium Sensor (NCS) proteins serves to modulate the functioning of the neuronal cells in response to changes in calcium levels, and prevent neuronal apoptosis. Structurally, all NCS proteins have 4 calcium-binding EF hand motifs, although EF1 does not bind to calcium in many members. All NCS proteins have an acyl modification at the N- terminus – where a myristoyl group is added post-translationally. Hippocalcin (HPCA) is an NCS protein, …

Responses Of Primate Frontal Cortex Neurons During Natural Vocal Communication, Cory T. Miller, A. Wren Thomas, Samuel U. Nummela, Lisa A. De La Mothe

Psychological Sciences and Counseling Faculty Research

The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed in chair-restrained animals. Here we recorded the activity of single neurons across multiple regions of prefrontal and premotor cortex while freely moving marmosets engaged in a natural vocal behavior known as antiphonal calling. Our …