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Carisbamate Blockade Of T-Type Voltage-Gated Calcium Channels, Do Young Kim, Fang-Xiong Zhang, Stan T. Nakanishi, Timothy Mettler, Ik-Hyun Cho, Younghee Ahn, Florian Hiess, Lina Chen, Patrick G. Sullivan, S. R. Wayne Chen, Gerald W. Zamponi, Jong M. Rho Apr 2017

Carisbamate Blockade Of T-Type Voltage-Gated Calcium Channels, Do Young Kim, Fang-Xiong Zhang, Stan T. Nakanishi, Timothy Mettler, Ik-Hyun Cho, Younghee Ahn, Florian Hiess, Lina Chen, Patrick G. Sullivan, S. R. Wayne Chen, Gerald W. Zamponi, Jong M. Rho

Spinal Cord and Brain Injury Research Center Faculty Publications

Objectives

Carisbamate (CRS) is a novel monocarbamate compound that possesses antiseizure and neuroprotective properties. However, the mechanisms underlying these actions remain unclear. Here, we tested both direct and indirect effects of CRS on several cellular systems that regulate intracellular calcium concentration [Ca2+]i.

Methods

We used a combination of cellular electrophysiologic techniques, as well as cell viability, Store Overload‐Induced Calcium Release (SOICR), and mitochondrial functional assays to determine whether CRS might affect [Ca2+]i levels through actions on the endoplasmic reticulum (ER), mitochondria, and/or T‐type voltage‐gated Ca2+ channels.

Results

In CA3 pyramidal neurons, kainic …


Rod-Shaped Microglia Morphology Is Associated With Aging In 2 Human Autopsy Series, Adam D. Bachstetter, Eseosa T. Ighodaro, Yasmin Hassoun, Danah Aldeiri, Janna H. Neltner, Ela Patel, Erin L. Abner, Peter T. Nelson Apr 2017

Rod-Shaped Microglia Morphology Is Associated With Aging In 2 Human Autopsy Series, Adam D. Bachstetter, Eseosa T. Ighodaro, Yasmin Hassoun, Danah Aldeiri, Janna H. Neltner, Ela Patel, Erin L. Abner, Peter T. Nelson

Spinal Cord and Brain Injury Research Center Faculty Publications

A subtype of microglia is defined by the morphological appearance of the cells as rod-shaped. Little is known about this intriguing cell type, as there are only a few case reports describing rod-shaped microglia in the neuropathological literature. Rod-shaped microglia were shown recently to account for a substantial proportion of the microglia cells in the hippocampus of both demented and cognitively intact aged individuals. We hypothesized that aging could be a defining feature in the occurrence of rod-shaped microglia. To test this hypothesis, two independent series of autopsy cases (total n=168 cases), which covered the adult lifespan from 20 – …


GabaB Receptor Attenuation Of GabaA Currents In Neurons Of The Mammalian Central Nervous System, Wen Shen, Changlong Nan, Peter T. Nelson, Harris Ripps, Malcolm M. Slaughter Mar 2017

GabaB Receptor Attenuation Of GabaA Currents In Neurons Of The Mammalian Central Nervous System, Wen Shen, Changlong Nan, Peter T. Nelson, Harris Ripps, Malcolm M. Slaughter

Pathology and Laboratory Medicine Faculty Publications

Ionotropic receptors are tightly regulated by second messenger systems and are often present along with their metabotropic counterparts on a neuron's plasma membrane. This leads to the hypothesis that the two receptor subtypes can interact, and indeed this has been observed in excitatory glutamate and inhibitory GABA receptors. In both systems the metabotropic pathway augments the ionotropic receptor response. However, we have found that the metabotropic GABAB receptor can suppress the ionotropic GABAA receptor current, in both the in vitro mouse retina and in human amygdala membrane fractions. Expression of amygdala membrane microdomains in Xenopus oocytes by microtransplantation …


Cytomegalovirus Serostatus, Inflammation, And Antibody Response To Influenza Vaccination In Older Adults: The Moderating Effect Of Beta Blockade, Rebecca G. Reed, Richard N. Greenberg, Suzanne C. Segerstrom Mar 2017

Cytomegalovirus Serostatus, Inflammation, And Antibody Response To Influenza Vaccination In Older Adults: The Moderating Effect Of Beta Blockade, Rebecca G. Reed, Richard N. Greenberg, Suzanne C. Segerstrom

Psychology Faculty Publications

Cytomegalovirus (CMV) has been implicated as a factor in immunosenescence, including poor antibody response to vaccination and higher immune activation and inflammation. Some people may be more or less vulnerable to the negative effects of CMV. The present investigation tested the effects of beta-blocker use and chronological age on the associations between CMV and immunity in adults aged 60–91 (N=98; 69% CMV seropositive) who were administered the trivalent influenza vaccine for up to 5 years. Peak antibody response, corrected for baseline, and spring (persistent) antibody response, corrected for peak, were assessed, as well as beta-2 microglobulin (β2μ) and interleukin-6 (IL-6). …


The Effect Of Sazetidine-A And Other Nicotinic Ligands On Nicotine Controlled Goal-Tracking In Female And Male Rats, S. Charntikov, A. M. Falco, K. Fink, Linda P. Dwoskin, R. A. Bevins Feb 2017

The Effect Of Sazetidine-A And Other Nicotinic Ligands On Nicotine Controlled Goal-Tracking In Female And Male Rats, S. Charntikov, A. M. Falco, K. Fink, Linda P. Dwoskin, R. A. Bevins

Pharmaceutical Sciences Faculty Publications

Nicotine is the primary addictive component of tobacco products and its complex stimulus effects are readily discriminated by humans and non-human animals. Previous preclinical research investigating directly the nature of the nicotine stimulus has been limited to male rodents. The current study began to address this significant gap in the literature by training female and male rats to discriminate 0.4 mg/kg nicotine from saline in the discriminated goal-tracking task. In this task, access to sucrose was intermittently available on nicotine session. On saline session, intermixed with nicotine sessions on separate days, sucrose was not available. Both sexes acquired the discrimination …


Safety And Improvement Of Movement Function After Stroke With Atomoxetine: A Pilot Randomized Trial, Andrea Ward, Cheryl Carrico, Elizabeth Powell, Philip M. Westgate, Laurie Nichols, Anne Fleischer, Lumy Sawaki Jan 2017

Safety And Improvement Of Movement Function After Stroke With Atomoxetine: A Pilot Randomized Trial, Andrea Ward, Cheryl Carrico, Elizabeth Powell, Philip M. Westgate, Laurie Nichols, Anne Fleischer, Lumy Sawaki

Physical Medicine and Rehabilitation Faculty Publications

Background: Intensive, task-oriented motor training has been associated with neuroplastic reorganization and improved upper extremity movement function after stroke. However, to optimize such training for people with moderate-to-severe movement impairment, pharmacological modulation of neuroplasticity may be needed as an adjuvant intervention.

Objective: Evaluate safety, as well as improvement in movement function, associated with motor training paired with a drug to upregulate neuroplasticity after stroke.

Methods: In this double-blind, randomized, placebo-controlled study, 12 subjects with chronic stroke received either atomoxetine or placebo paired with motor training. Safety was assessed using vital signs. Upper extremity movement function was assessed using Fugl-Meyer Assessment, …


A Cognitive Electrophysiological Signature Differentiates Amnestic Mild Cognitive Impairment From Normal Aging, Juan Li, Lucas S. Broster, Gregory A. Jicha, Nancy B. Munro, Frederick A. Schmitt, Erin L. Abner, Richard J. Kryscio, Charles D. Smith, Yang Jiang Jan 2017

A Cognitive Electrophysiological Signature Differentiates Amnestic Mild Cognitive Impairment From Normal Aging, Juan Li, Lucas S. Broster, Gregory A. Jicha, Nancy B. Munro, Frederick A. Schmitt, Erin L. Abner, Richard J. Kryscio, Charles D. Smith, Yang Jiang

Behavioral Science Faculty Publications

Background: Noninvasive and effective biomarkers for early detection of amnestic mild cognitive impairment (aMCI) before measurable changes in behavioral performance remain scarce. Cognitive event-related potentials (ERPs) measure synchronized synaptic neural activity associated with a cognitive event. Loss of synapses is a hallmark of the neuropathology of early Alzheimer’s disease (AD). In the present study, we tested the hypothesis that ERP responses during working memory retrieval discriminate aMCI from cognitively normal controls (NC) matched in age and education.

Methods: Eighteen NC, 17 subjects with aMCI, and 13 subjects with AD performed a delayed match-to-sample task specially designed not only to be …


Neuropathological And Genetic Correlates Of Survival And Dementia Onset In Synucleinopathies: A Retrospective Analysis, David J. Irwin, Murray Grossman, Daniel Weintraub, Howard I. Hurtig, John E. Duda, Sharon X. Xie, Edward B. Lee, Vivianna M. Van Deerlin, Oscar L. Lopez, Julia K. Kofler, Peter T. Nelson, Gregory A. Jicha, Randy Woltjer, Joseph F. Quinn, Jeffery Kaye, James B. Leverenz, Debby Tsuang, Katelan Longfellow, Dora Yearout, Walter Kukull, C. Dirk Keene, Thomas J. Montine, Cyrus P. Zabetian, John Q. Trojanowski Jan 2017

Neuropathological And Genetic Correlates Of Survival And Dementia Onset In Synucleinopathies: A Retrospective Analysis, David J. Irwin, Murray Grossman, Daniel Weintraub, Howard I. Hurtig, John E. Duda, Sharon X. Xie, Edward B. Lee, Vivianna M. Van Deerlin, Oscar L. Lopez, Julia K. Kofler, Peter T. Nelson, Gregory A. Jicha, Randy Woltjer, Joseph F. Quinn, Jeffery Kaye, James B. Leverenz, Debby Tsuang, Katelan Longfellow, Dora Yearout, Walter Kukull, C. Dirk Keene, Thomas J. Montine, Cyrus P. Zabetian, John Q. Trojanowski

Sanders-Brown Center on Aging Faculty Publications

Background

Great heterogeneity exists in survival and the interval between onset of motor symptoms and dementia symptoms across synucleinopathies. We aimed to identify genetic and pathological markers that have the strongest association with these features of clinical heterogeneity in synucleinopathies.

Methods

In this retrospective study, we examined symptom onset, and genetic and neuropathological data from a cohort of patients with Lewy body disorders with autopsy-confirmed α synucleinopathy (as of Oct 1, 2015) who were previously included in other studies from five academic institutions in five cities in the USA. We used histopathology techniques and markers to assess the burden of …


Reduced Efficacy Of Anti-AΒ Immunotherapy In A Mouse Model Of Amyloid Deposition And Vascular Cognitive Impairment Comorbidity, Erica M. Weekman, Tiffany L. Sudduth, Carly N. Caverly, Timothy J. Kopper, Oliver W. Phillips, David K. Powell, Donna M. Wilcock Sep 2016

Reduced Efficacy Of Anti-AΒ Immunotherapy In A Mouse Model Of Amyloid Deposition And Vascular Cognitive Impairment Comorbidity, Erica M. Weekman, Tiffany L. Sudduth, Carly N. Caverly, Timothy J. Kopper, Oliver W. Phillips, David K. Powell, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Vascular cognitive impairment and dementia (VCID) is the second most common form of dementia behind Alzheimer's disease (AD). It is estimated that 40% of AD patients also have some form of VCID. One promising therapeutic for AD is anti-Aβ immunotherapy, which uses antibodies against Aβ to clear it from the brain. While successful in clearing Aβ and improving cognition in mice, anti-Aβ immunotherapy failed to reach primary cognitive outcomes in several different clinical trials. We hypothesized that one potential reason the anti-Aβ immunotherapy clinical trials were unsuccessful was due to this high percentage of VCID …


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 Jun 2016

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 …


Associative Spike Timing-Dependent Potentiation Of The Basal Dendritic Excitatory Synapses In The Hippocampus In Vivo., Thomas K Fung, Clayton S Law, L Stan Leung Jun 2016

Associative Spike Timing-Dependent Potentiation Of The Basal Dendritic Excitatory Synapses In The Hippocampus In Vivo., Thomas K Fung, Clayton S Law, L Stan Leung

Physiology and Pharmacology Publications

Spike timing-dependent plasticity in the hippocampus has rarely been studied in vivo. Using extracellular potential and current source density analysis in urethane-anesthetized adult rats, we studied synaptic plasticity at the basal dendritic excitatory synapse in CA1 after excitation-spike (ES) pairing; E was a weak basal dendritic excitation evoked by stratum oriens stimulation, and S was a population spike evoked by stratum radiatum apical dendritic excitation. We hypothesize that positive ES pairing-generating synaptic excitation before a spike-results in long-term potentiation (LTP) while negative ES pairing results in long-term depression (LTD). Pairing (50 pairs at 5 Hz) at ES intervals of -10 …


Diffuse Traumatic Brain Injury Induces Prolonged Immune Sysregulation And Potentiates Hyperalgesia Following A Peripheral Immune Challenge, Rachel K. Rowe, Gavin I. Ellis, Jordan L. Harrison, Adam D. Bachstetter, Gregory F. Corder, Linda J. Van Eldik, Bradley K. Taylor, Francesc Marti, Jonathan Lifshitz May 2016

Diffuse Traumatic Brain Injury Induces Prolonged Immune Sysregulation And Potentiates Hyperalgesia Following A Peripheral Immune Challenge, Rachel K. Rowe, Gavin I. Ellis, Jordan L. Harrison, Adam D. Bachstetter, Gregory F. Corder, Linda J. Van Eldik, Bradley K. Taylor, Francesc Marti, Jonathan Lifshitz

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: Nociceptive and neuropathic pain occurs as part of the disease process after traumatic brain injury (TBI) in humans. Central and peripheral inflammation, a major secondary injury process initiated by the traumatic brain injury event, has been implicated in the potentiation of peripheral nociceptive pain. We hypothesized that the inflammatory response to diffuse traumatic brain injury potentiates persistent pain through prolonged immune dysregulation.

Results: To test this, adult, male C57BL/6 mice were subjected to midline fluid percussion brain injury or to sham procedure. One cohort of mice was analyzed for inflammation-related cytokine levels in cortical biopsies and serum along an …


Effects Of Lesions Of The Bed Nucleus Of The Stria Terminalis, Laterual Hypothalamus, Or Insular Cortex On Conditioned Taste Aversion And Conditioned Odor Aversion, Christopher T. Roman, Nino Nebieridze, Aristides Sastre, Steve Reilly Mar 2016

Effects Of Lesions Of The Bed Nucleus Of The Stria Terminalis, Laterual Hypothalamus, Or Insular Cortex On Conditioned Taste Aversion And Conditioned Odor Aversion, Christopher T. Roman, Nino Nebieridze, Aristides Sastre, Steve Reilly

Christopher Roman

The effects of permanent forebrain lesions on conditioned taste aversions (CTAs) and conditioned odor aversions (COAs) were examined in 3 experiments. In Experiment 1, lesions of the bed nucleus of the stria terminalis had no influence on CTA or COA acquisition. Although lesions of the lateral hypothalamus induced severe hypodipsia in Experiment 2, they did not prevent the acquisition of CTAs or COAs. Finally, in Experiment 3, lesions of the insular cortex retarded CTA acquisition but had no influence on COA acquisition. The implications of these findings are discussed with regard to the forebrain influence on parabrachial nucleus function during …


AΒ40 Reduces P-Glycoprotein At The Blood-Brain Barrier Through The Ubiquitin-Proteasome Pathway, Anika M. S. Hartz, Yu Zhong, Andrea Wolf, Harry Levine Iii, David S. Miller, Björn Bauer Feb 2016

AΒ40 Reduces P-Glycoprotein At The Blood-Brain Barrier Through The Ubiquitin-Proteasome Pathway, Anika M. S. Hartz, Yu Zhong, Andrea Wolf, Harry Levine Iii, David S. Miller, Björn Bauer

Sanders-Brown Center on Aging Faculty Publications

Failure to clear amyloid-β (Aβ) from the brain is in part responsible for Aβ brain accumulation in Alzheimer's disease (AD). A critical protein for clearing Aβ across the blood–brain barrier is the efflux transporter P-glycoprotein (P-gp) in the luminal plasma membrane of the brain capillary endothelium. P-gp is reduced at the blood–brain barrier in AD, which has been shown to be associated with Aβ brain accumulation. However, the mechanism responsible for P-gp reduction in AD is not well understood. Here we focused on identifying critical mechanistic steps involved in reducing P-gp in AD. We …


Blockade Of Astrocytic Calcineurin/Nfat Signaling Helps To Normalize Hippocampal Synaptic Function And Plasticity In A Rat Model Of Traumatic Brain Injury, Jennifer L. Furman, Pradoldej Sompol, Susan D. Kraner, Melanie M. Pleiss, Esther J. Putman, Jacob Dunkerson, Hafiz Mohmmad Abdul, Kelly N. Roberts, Stephen William Scheff, Christopher M. Norris Feb 2016

Blockade Of Astrocytic Calcineurin/Nfat Signaling Helps To Normalize Hippocampal Synaptic Function And Plasticity In A Rat Model Of Traumatic Brain Injury, Jennifer L. Furman, Pradoldej Sompol, Susan D. Kraner, Melanie M. Pleiss, Esther J. Putman, Jacob Dunkerson, Hafiz Mohmmad Abdul, Kelly N. Roberts, Stephen William Scheff, Christopher M. Norris

Pharmacology and Nutritional Sciences Faculty Publications

Increasing evidence suggests that the calcineurin (CN)-dependent transcription factor NFAT (Nuclear Factor of Activated T cells) mediates deleterious effects of astrocytes in progressive neurodegenerative conditions. However, the impact of astrocytic CN/NFAT signaling on neural function/recovery after acute injury has not been investigated extensively. Using a controlled cortical impact (CCI) procedure in rats, we show that traumatic brain injury is associated with an increase in the activities of NFATs 1 and 4 in the hippocampus at 7 d after injury. NFAT4, but not NFAT1, exhibited extensive labeling in astrocytes and was found throughout the axon/dendrite layers of CA1 and the dentate …


Chronic Systemic Immune Dysfunction In African-Americans With Small Vessel-Type Ischemic Stroke, Candice M. Brown, Cheryl D. Bushnell, Gregory P. Samsa, Larry B. Goldstein, Carol A. Colton Dec 2015

Chronic Systemic Immune Dysfunction In African-Americans With Small Vessel-Type Ischemic Stroke, Candice M. Brown, Cheryl D. Bushnell, Gregory P. Samsa, Larry B. Goldstein, Carol A. Colton

Neurology Faculty Publications

The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 weeks post-stroke compared to control individuals. Cases were African-Americans with lacunar stroke (n = 30), and controls were age-matched African-Americans with no history of stroke or other major neurologic disease (n = 37). Blood was obtained > 6 weeks post-stroke and was analyzed for inflammatory biomarkers. Freshly isolated peripheral blood mononuclear cells were stimulated with lipopolysaccharide …


Disease-Related Microglia Heterogeneity In The Hippocampus Of Alzheimer's Disease, Dementia With Lewy Bodies, And Hippocampal Sclerosis Of Aging, Adam D. Bachstetter, Linda J. Van Eldik, Frederick A. Schmitt, Janna H. Neltner, Eseosa T. Ighodaro, Scott J. Webster, Ela Patel, Erin L. Abner, Richard J. Kryscio, Peter T. Nelson May 2015

Disease-Related Microglia Heterogeneity In The Hippocampus Of Alzheimer's Disease, Dementia With Lewy Bodies, And Hippocampal Sclerosis Of Aging, Adam D. Bachstetter, Linda J. Van Eldik, Frederick A. Schmitt, Janna H. Neltner, Eseosa T. Ighodaro, Scott J. Webster, Ela Patel, Erin L. Abner, Richard J. Kryscio, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Introduction: Neuropathological, genetic, and biochemical studies have provided support for the hypothesis that microglia participate in Alzheimer's disease (AD) pathogenesis. Despite the extensive characterization of AD microglia, there are still many unanswered questions, and little is known about microglial morphology in other common forms of age-related dementia: particularly, dementia with Lewy bodies (DLB) and hippocampal sclerosis of aging (HS-Aging). In addition, no prior studies have attempted to compare and contrast the microglia morphology in the hippocampus of various neurodegenerative conditions.

Results: Here we studied cases with pathologically-confirmed AD (n = 7), HS-Aging (n = 7), AD + HS-aging …


Multimodal Frontostriatal Connectivity Underlies Individual Differences In Self-Esteem, Robert S. Chavez, Todd F. Heatherton May 2015

Multimodal Frontostriatal Connectivity Underlies Individual Differences In Self-Esteem, Robert S. Chavez, Todd F. Heatherton

Dartmouth Scholarship

A heightened sense of self-esteem is associated with a reduced risk for several types of affective and psychiatric disorders, including depression, anxiety and eating disorders. However, little is known about how brain systems integrate self-referential processing and positive evaluation to give rise to these feelings. To address this, we combined diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) to test how frontostriatal connectivity reflects long-term trait and short-term state aspects of self-esteem. Using DTI, we found individual variability in white matter structural integrity between the medial prefrontal cortex and the ventral striatum was related to trait measures of …


Belief About Nicotine Selectively Modulates Value And Reward Prediction Error Signals In Smokers, Xiaosi Gu, Terry Lohrenz, Ramiro Salas, Philip R. Baldwin, Alireza Soltani Feb 2015

Belief About Nicotine Selectively Modulates Value And Reward Prediction Error Signals In Smokers, Xiaosi Gu, Terry Lohrenz, Ramiro Salas, Philip R. Baldwin, Alireza Soltani

Dartmouth Scholarship

Little is known about how prior beliefs impact biophysically described processes in the presence of neuroactive drugs, which presents a profound challenge to the understanding of the mechanisms and treatments of addiction. We engineered smokers' prior beliefs about the presence of nicotine in a cigarette smoked before a functional magnetic resonance imaging session where subjects carried out a sequential choice task. Using a model-based approach, we show that smokers' beliefs about nicotine specifically modulated learning signals (value and reward prediction error) defined by a computational model of mesolimbic dopamine systems. Belief of "no nicotine in cigarette" (compared with "nicotine in …


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 Jan 2015

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. …


Dissociation Between Face Perception And Face Memory In Adults, But Not Children, With Developmental Prosopagnosia, Kirsten A. Dalrymple, Lúcia Garrido, Brad Duchaine Oct 2014

Dissociation Between Face Perception And Face Memory In Adults, But Not Children, With Developmental Prosopagnosia, Kirsten A. Dalrymple, Lúcia Garrido, Brad Duchaine

Dartmouth Scholarship

Cognitive models propose that face recognition is accomplished through a series of discrete stages, including perceptual representation of facial structure, and encoding and retrieval of facial information. This implies that impaired face recognition can result from failures of face perception, face memory, or both. Studies of acquired prosopagnosia, autism spectrum disorders, and the development of normal face recognition support the idea that face perception and face memory are distinct processes, yet this distinction has received little attention in developmental prosopagnosia (DP). To address this issue, we tested the face perception and face memory of children and adults with DP. By …


Large-Scale Identification Of Chemically Induced Mutations In Drosophila Melanogaster., Nele A Haelterman, Lichun Jiang, Yumei Li, Vafa Bayat, Hector Sandoval, Berrak Ugur, Kai Li Tan, Ke Zhang, Danqing Bei, Bo Xiong, Wu-Lin Charng, Theodore Busby, Adeel Jawaid, Gabriela David, Manish Jaiswal, Koen J T Venken, Shinya Yamamoto, Rui Chen, Hugo J Bellen Oct 2014

Large-Scale Identification Of Chemically Induced Mutations In Drosophila Melanogaster., Nele A Haelterman, Lichun Jiang, Yumei Li, Vafa Bayat, Hector Sandoval, Berrak Ugur, Kai Li Tan, Ke Zhang, Danqing Bei, Bo Xiong, Wu-Lin Charng, Theodore Busby, Adeel Jawaid, Gabriela David, Manish Jaiswal, Koen J T Venken, Shinya Yamamoto, Rui Chen, Hugo J Bellen

Faculty Publications

Forward genetic screens using chemical mutagens have been successful in defining the function of thousands of genes in eukaryotic model organisms. The main drawback of this strategy is the time-consuming identification of the molecular lesions causative of the phenotypes of interest. With whole-genome sequencing (WGS), it is now possible to sequence hundreds of strains, but determining which mutations are causative among thousands of polymorphisms remains challenging. We have sequenced 394 mutant strains, generated in a chemical mutagenesis screen, for essential genes on the Drosophila X chromosome and describe strategies to reduce the number of candidate mutations from an average of …


Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio Jun 2014

Self-Reported Head Injury And Risk Of Late-Life Impairment And Ad Pathology In An Ad Center Cohort, Erin L. Abner, Peter T. Nelson, Frederick A. Schmitt, Steven R. Browning, David W. Fardo, Lijie Wan, Gregory A. Jicha, Gregory E. Cooper, Charles D. Smith, Allison M. Caban-Holt, Linda J. Van Eldik, Richard J. Kryscio

Sanders-Brown Center on Aging Faculty Publications

Aims: To evaluate the relationship between self-reported head injury and cognitive impairment, dementia, mortality, and Alzheimer's disease (AD)-type pathological changes. Methods: Clinical and neuropathological data from participants enrolled in a longitudinal study of aging and cognition (n = 649) were analyzed to assess the chronic effects of self-reported head injury. Results: The effect of self-reported head injury on the clinical state depended on the age at assessment: for a 1-year increase in age, the OR for the transition to clinical mild cognitive impairment (MCI) at the next visit for participants with a history of head injury was 1.21 and 1.34 …


The N400 As An Index Of Racial Stereotype Accessibility, Eric Hehman, Hannah I. Volpert, Robert F. Simons Mar 2014

The N400 As An Index Of Racial Stereotype Accessibility, Eric Hehman, Hannah I. Volpert, Robert F. Simons

Dartmouth Scholarship

The current research examined the viability of the N400, an event-related potential (ERP) related to the detection of semantic incongruity, as an index of both stereotype accessibility and interracial prejudice. Participants’ EEG was recorded while they completed a sequential priming task, in which negative or positive, stereotypically black (African American) or white (Caucasian American) traits followed the presentation of either a black or white face acting as a prime. ERP examination focused on the N400, but additionally examined N100 and P200 reactivity. Replicating and extending previous N400 stereotype research, results indicated that the N400 can indeed function as an index …


Enrichment And Training Improve Cognition In Rats With Cortical Malformations, Kyle R. Jenks, Marcella M. Lucas, Ben A. Duffy, Ashlee A. Robbins, Barjor Gimi, Jeremy M. Barry, Rod C. Scott Dec 2013

Enrichment And Training Improve Cognition In Rats With Cortical Malformations, Kyle R. Jenks, Marcella M. Lucas, Ben A. Duffy, Ashlee A. Robbins, Barjor Gimi, Jeremy M. Barry, Rod C. Scott

Dartmouth Scholarship

Children with malformations of cortical development (MCD) frequently have associated cognitive impairments which reduce quality of life. We hypothesized that cognitive deficits associated with MCD can be improved with environmental manipulation or additional training. The E17 methylazoxymethanol acetate (MAM) exposure model bears many anatomical hallmarks seen in human MCDs as well as similar behavioral and cognitive deficits. We divided control and MAM exposed Sprague-Dawley rats into enriched and non-enriched groups and tested performance in the Morris water maze. Another group similarly divided underwent sociability testing and also underwent Magnetic Resonance Imaging (MRI) scans pre and post enrichment. A third group …


Short Duration Waveforms Recorded Extracellularly From Freely Moving Rats Are Representative Of Axonal Activity, Ashlee A. Robbins, Steven E. Fox, Gregory L. Holmes, Rod C. Scott, Jeremy M. Barry Nov 2013

Short Duration Waveforms Recorded Extracellularly From Freely Moving Rats Are Representative Of Axonal Activity, Ashlee A. Robbins, Steven E. Fox, Gregory L. Holmes, Rod C. Scott, Jeremy M. Barry

Dartmouth Scholarship

While extracellular somatic action potentials from freely moving rats have been well characterized, axonal activity has not. We report direct extracellular tetrode recordings of putative axons whose principal feature is a short duration waveform (SDW) with an average peak-trough length less than 179 μs. While SDW recordings using tetrodes have previously been treated as questionable or classified as cells, we hypothesize that they are representative of axonal activity. These waveforms have significantly shorter duration than somatic action potentials, are triphasic and are therefore similar to classic descriptions of microelectrode recordings in white matter and of in vitro action potential propagation …


Socially Excluded Individuals Fail To Recruit Medial Prefrontal Cortex For Negative Social Scenes, Katherine E. Powers, Dylan D. Wagner, Catherine J. Norris, Todd F. Heatherton Nov 2013

Socially Excluded Individuals Fail To Recruit Medial Prefrontal Cortex For Negative Social Scenes, Katherine E. Powers, Dylan D. Wagner, Catherine J. Norris, Todd F. Heatherton

Dartmouth Scholarship

Converging behavioral evidence suggests that people respond to experiences of social exclusion with both defensive and affiliative strategies, allowing them to avoid further distress while also encouraging re-establishment of positive social connections. However, there are unresolved questions regarding the cognitive mechanisms underlying people's responses to social exclusion. Here, we sought to gain insight into these behavioral tendencies by using functional magnetic resonance imaging (fMRI) to examine the impact of social exclusion on neural responses to visual scenes that varied on dimensions of sociality and emotional valence. Compared to socially included participants, socially excluded participants failed to recruit dorsomedial prefrontal cortex …


The Flexible Fairness: Equality, Earned Entitlement, And Self-Interest, Chunliang Feng, Yi Luo, Ruolei Gu, Lucas S. Broster, Xueyi Shen, Tengxiang Tian, Yue-Jia Luo, Frank Krueger Sep 2013

The Flexible Fairness: Equality, Earned Entitlement, And Self-Interest, Chunliang Feng, Yi Luo, Ruolei Gu, Lucas S. Broster, Xueyi Shen, Tengxiang Tian, Yue-Jia Luo, Frank Krueger

Behavioral Science Faculty Publications

The current study explored whether earned entitlement modulated the perception of fairness in three experiments. A preliminary resource earning task was added before players decided how to allocate the resource they jointly earned. Participants' decision in allocation, their responses to equal or unequal offers, whether advantageous or disadvantageous, and subjective ratings of fairness were all assessed in the current study. Behavioral results revealed that participants proposed more generous offers and showed enhanced tolerance to disadvantageous unequal offers from others when they performed worse than their presumed "partners," while the reverse was true in the better-performance condition. The subjective ratings also …


Self-Regulatory Depletion Increases Emotional Reactivity In The Amygdala, Dylan D. Wagner, Todd F. Heatherton Aug 2013

Self-Regulatory Depletion Increases Emotional Reactivity In The Amygdala, Dylan D. Wagner, Todd F. Heatherton

Dartmouth Scholarship

The ability to self-regulate can become impaired when people are required to engage in successive acts of effortful self-control, even when self-control occurs in different domains. Here, we used functional neuroimaging to test whether engaging in effortful inhibition in the cognitive domain would lead to putative dysfunction in the emotional domain. Forty-eight participants viewed images of emotional scenes during functional magnetic resonance imaging in two sessions that were separated by a challenging attention control task that required effortful inhibition (depletion group) or not (control group). Compared to the control group, depleted participants showed increased activity in the left amygdala to …


Prefrontal Cortical Microcircuits Bind Perception To Executive Control, Ioan Opris, Lucas Santos, Greg A. Gerhardt, Dong Song, Theodore W. Berger, Robert E. Hampson, Sam A. Deadwyler Jul 2013

Prefrontal Cortical Microcircuits Bind Perception To Executive Control, Ioan Opris, Lucas Santos, Greg A. Gerhardt, Dong Song, Theodore W. Berger, Robert E. Hampson, Sam A. Deadwyler

Neuroscience Faculty Publications

During the perception-to-action cycle, our cerebral cortex mediates the interactions between the environment and the perceptual-executive systems of the brain. At the top of the executive hierarchy, prefrontal cortical microcircuits are assumed to bind perceptual and executive control information to guide goal-driven behavior. Here, we tested this hypothesis by comparing simultaneously recorded neuron firing in prefrontal cortical layers and the caudate-putamen of rhesus monkeys, trained in a spatial-versus-object, rule-based match-to-sample task. We found that during the perception and executive selection phases, cell firing in the localized prefrontal layers and caudate-putamen region exhibited similar location preferences on spatial-trials, but less on …