DOCSLIB.ORG

Cognitive Aging Is Associated with Redistribution of Synaptic Weights in the Hippocampus

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cognitive Aging Is Associated with Redistribution of Synaptic Weights in the Hippocampus Cognitive aging is associated with redistribution of synaptic weights in the hippocampus Eric W. Bussa,1, Nicola J. Corbetta,1, Joshua G. Robertsa, Natividad Ybarraa, Timothy F. Musiala, Dina Simkinb, Elizabeth Molina-Camposa, Kwang-Jin Oha, Lauren L. Nielsena, Gelique D. Ayalaa, Sheila A. Mullena, Anise K. Farooqia, Gary X. D’Souzaa, Corinne L. Hilla, Linda A. Beana, Annalise E. Rogalskya, Matthew L. Russoa, Dani M. Curlikb, Marci D. Antionb, Craig Weissb, Dane M. Chetkovichc, M. Matthew Ohb, John F. Disterhoftb,2, and Daniel A. Nicholsona,2 aDepartment of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612; bDepartment of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611; and cDepartment of Neurology, Vanderbilt University Medical Center, Nashville, TN 37232 Edited by Carol A. Barnes, University of Arizona, Tucson, AZ, and approved January 19, 2021 (received for review December 6, 2019) Behaviors that rely on the hippocampus are particularly susceptible 11), cognitive aging within hippocampus-dependent forms of learn- to chronological aging, with many aged animals (including humans) ing and memory are relatively independent of those that engage the maintaining cognition at a young adult-like level, but many others prefrontal/orbitofrontal cortical neural systems (6–9, 12–15). the same age showing marked impairments. It is unclear whether Neither the mechanisms underlying the conservation of memory the ability to maintain cognition over time is attributable to brain function across chronological aging nor those contributing to the maintenance, sufficient cognitive reserve, compensatory changes in age-related emergence and exacerbation of memory impairments network function, or some combination thereof. While network dys- are clearly understood for either neurocognitive system. It is clear, function within the hippocampal circuit of aged, learning-impaired however, that neither frank neuronal loss (16, 17) nor overall animals is well-documented, its neurobiological substrates remain synapse loss (18) contributes to cognitive aging within the medial elusive. Here we show that the synaptic architecture of hippocampal temporal lobe/hippocampal memory system. Rather, the intrigu- regions CA1 and CA3 is maintained in a young adult-like state in ing idea that has emerged from work in both the hippocampal and aged rats that performed comparably to their young adult counter- the prefrontal/orbitofrontal cortical memory systems is that there parts in both trace eyeblink conditioning and Morris water maze are functional alterations in the synaptic connections in individual NEUROSCIENCE learning. In contrast, among learning-impaired, but equally aged microcircuits embedded within these larger neuroanatomical rats, we found that a redistribution of synaptic weights amplifies systems (6–10, 19–31). the influence of autoassociational connections among CA3 pyramidal Axospinous synapses (including those in hippocampal and neurons, yet reduces the synaptic input onto these same neurons cortical circuits) are characterized on the basis of the three- from the dentate gyrus. Notably, synapses within hippocampal re- dimensional morphology of their postsynaptic densities (PSDs) gion CA1 showed no group differences regardless of cognitive abil- (20, 32–34). The most-abundant axospinous synaptic subtype has a ity. Taking the data together, we find the imbalanced synaptic weights within hippocampal CA3 provide a substrate that can explain Significance the abnormal firing characteristics of both CA3 and CA1 pyramidal neurons in aged, learning-impaired rats. Furthermore, our work pro- A longstanding question in the field of the neurobiology of vides some clarity with regard to how some animals cognitively age learning and memory is why some aged individuals perform successfully, while others’ lifespans outlast their “mindspans.” comparably to young adults in learning and memory tasks, whereas others show impairments that resemble the perfor- synapse | aging | hippocampus | cognition mance of those with hippocampal damage. Answers to this question have been critical for advancing our understanding ging is the biggest risk factor for Alzheimer’s disease, but of, and our ability to treat, aging-related cognitive impair- Amany aged individuals nevertheless retain the ability to ments. Here, we have exploited the exquisite organization of perform cognitive tasks with young adult (YA)-like competency, the hippocampal circuit to reveal that “unsuccessful” cognitive and are thus resilient to age-related cognitive decline and de- aging is associated with a breakdown of young adult-like cir- mentias (1, 2). The mechanisms of such resilience are unknown, cuit organization, and provide a remarkably straightforward but are thought to involve neural or cognitive reserve, brain net- potential cellular substrate for the well-documented dysfunc- work adaptations, or simply the ability to maintain cognitive brain tion in neuronal encoding of hippocampal CA1 and CA3 pyra- circuits in a YA-like state (3–5). Much of the cellular and func- midal neurons in aged learning-impaired rats. tional insight into the concept or risk of/resilience against age- related cognitive impairments has come from animal models of Author contributions: J.F.D. and D.A.N. designed research; E.W.B., N.J.C., J.G.R., N.Y., normal/nonpathological aging (6–10). Many of these studies have T.F.M., D.S., E.M.-C., K.-J.O., L.L.N., G.D.A., S.A.M., A.K.F., G.X.D., C.L.H., L.A.B., A.E.R., M.L.R., D.M. Curlik, M.D.A., C.W., M.M.O., and D.A.N. performed research; D.M. Chetko- shown that circuit function abnormalities are associated with be- vich and D.A.N. contributed new reagents/analytic tools; E.W.B., N.J.C., J.G.R., N.Y., T.F.M., havioral impairments. The cellular and structural bases for such D.S., E.M.-C., K.-J.O., L.L.N., G.D.A., S.A.M., A.K.F., G.X.D., C.L.H., L.A.B., A.E.R., M.L.R., D.M. functional aberrations, however, remain largely unknown. Curlik, M.D.A., C.W., D.M. Chetkovich, M.M.O., J.F.D., and D.A.N. analyzed data; and Two of the most well-studied cognitive domains that show E.W.B., N.J.C., M.L.R., M.M.O., J.F.D., and D.A.N. wrote the paper. susceptibility to chronological aging in both rodents and nonhu- The authors declare no competing interest. man primates are working memory and spatial/temporal memory This article is a PNAS Direct Submission. (6–10). Importantly, these cognitive domains engage anatomically Published under the PNAS license. distinct neurocognitive systems, with the former relying on pre- 1E.W.B. and N.J.C. contributed equally to this work. frontal/orbitofrontal cortical circuits and the latter relying on 2To whom correspondence may be addressed. Email: [email protected] or hippocampal circuitry. Interestingly, although behavioral deficits [email protected]. in these two domains (in the case of rat models of cognitive aging) This article contains supporting information online at https://www.pnas.org/lookup/suppl/ begin to emerge, worsen, and become increasingly prevalent be- doi:10.1073/pnas.1921481118/-/DCSupplemental. tween 12 and 18 mo of age in most strains (reviewed in refs. 9 and Published February 15, 2021. PNAS 2021 Vol. 118 No. 8 e1921481118 https://doi.org/10.1073/pnas.1921481118 | 1of10 Downloaded by guest on September 29, 2021 continuous, macular, disk-shaped PSD, as compared to the less- only AMPARs, only perforated axospinous synapses, and only abundant perforated synaptic subtype, which has at least one dis- hippocampal region CA3, which together shift the balance of continuity in its PSD (34). In addition to differing substantially with synaptic weights that drive action potential output in CA3 py- regard to relative frequency, perforated and nonperforated synap- ramidal neurons maladaptively toward an overemphasis of the ses also harbor major differences in size and synaptic AMPA-type autoassociational synapses that interconnect CA3 pyramidal and NMDA-type receptor expression levels (AMPAR and neurons. NMDAR, respectively) (34–38). There is also evidence that per- forated and nonperforated synapses are differentially involved in Results synaptic plasticity (39–44) and in preservation of—or reduc- Spontaneous Excitatory Postsynaptic Potential Amplitude Is Elevated tions in—memory function during chronological aging (6, 20, in Aged CA3, but Not CA1, Pyramidal Neurons. We recorded spon- 45). Layered onto these general distinctions between perfo- taneous excitatory postsynaptic potentials (sEPSPs) from hippo- rated and nonperforated synapses are more specific differences campal pyramidal neurons of YA (6- to 8-mo old) and aged (28- in their characteristics when considered within neural circuits. to 31-mo old) rats from regions CA1 and CA3, which many studies For example, perforated synapses have a stronger and more have implicated in age-related learning and memory impairments consistent influence on neuronal computation within hippo- (6–10) (Fig. 1A). These rats, unlike all others studied here, were campal region CA1 than their nonperforated counterparts, which not behaviorally characterized. Although sEPSP amplitude was nevertheless outnumber the former by a roughly 9-to-1 ratio (34, similar in pyramidal neurons from YA and aged rats in region 46, 47). CA1 (Fig. 1A), CA3 pyramidal neurons from aged rats had sig- These and other circuit-specific differences necessitate a nificantly higher sEPSP amplitudes as compared to those from circuit-based approach to understanding the synaptic
Load more

Recommended publications
  • Transsynaptic Modulation of Presynaptic Short-Term Plasticity Induction in Hippocampal Mossy Fiber Synapses
    bioRxiv preprint doi: https://doi.org/10.1101/2020.10.25.353953; this version posted October 25, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Transsynaptic modulation of presynaptic short-term plasticity induction in hippocampal mossy fiber synapses David Vandael1,2, Yuji Okamoto1, and Peter Jonas2 Cellular Neuroscience, IST Austria (Institute of Science and Technology Austria), Am Campus 1, A-3400 Klosterneuburg, Austria 1 These authors contributed equally. 2 Corresponding authors. E-mail: [email protected] or [email protected] Corresponding author: Dr. David Vandael Dr. Peter Jonas IST Austria (Institute of Science and Technology Austria) Cellular Neuroscience, Am Campus 1 A-3400 Klosterneuburg, Austria Phone: 0043-2243-9000-3700 Fax: 0043-2243-9000-2007 E-mail: [email protected] E-mail: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.10.25.353953; this version posted October 25, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. SUMMARY The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit of the hippocampus. Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this synaptic connection. It is widely believed that mossy fiber PTP is an entirely presynaptic phenomenon, implying that PTP induction is input-specific, and requires neither activity of multiple inputs nor stimulation of postsynaptic neurons for induction.
    [Show full text]
  • Risk Factors for the Progression of Mild Cognitive Impairment to Dementia
    HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Clin Geriatr Manuscript Author Med. Author Manuscript Author manuscript; available in PMC 2018 April 24. Published in final edited form as: Clin Geriatr Med. 2013 November ; 29(4): 873–893. doi:10.1016/j.cger.2013.07.009. Risk Factors for the Progression of Mild Cognitive Impairment to Dementia Noll L. Campbell, PharmDa,b,c,d,*, Fred Unverzagt, PhDe, Michael A. LaMantia, MD, MPHb,c,f, Babar A. Khan, MD, MSb,c,f, and Malaz A. Boustani, MD, MPHb,c,f aDepartment of Pharmacy Practice, College of Pharmacy, Purdue University, West Lafayette, IN, USA bIndiana University Center for Aging Research, Indianapolis, IN, USA cRegenstrief Institute, Inc, Indianapolis, IN, USA dDepartment of Pharmacy, Wishard Health Services, Indianapolis, IN, USA eDepartment of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA fDepartment of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA Keywords Mild cognitive impairment; Dementia; Risk factors; Genetics; Biomarkers Introduction As identified in previously published articles, including those published in this issue, the detection of early cognitive impairment among older adult populations is worthy of diagnostic and clinical recognition. Several definitions and classifications have been applied to this form of cognitive impairment over time1–4 including mild cognitive impairment (MCI),4–6 cognitive impairment no dementia,7,8 malignant senescent forgetfulness,9 and age-associated cognitive decline.10
    [Show full text]
  • Use of Neurotechnology in Normal Brain Aging and Alzheimer
    Use of Neurotechnology in Normal Brain Aging and Alzheimer’s Disease (AD) and AD-Related Dementias (ADRD) NIA Virtual Workshop Division of Neuroscience April 27, 2020 Final June 1, 2020 This meeting summary was prepared by Dave Frankowski, Rose Li and Associates, Inc., under contract to the National Institute on Aging (NIA). The views expressed in this document reflect both individual and collective opinions of the focus group participants an d not necessarily those of NIA. Review of earlier versions of this meeting summary by the following individuals is gratefully acknowledged: Ali Abedi, Ed Boyden, Dana Carluccio, Monica Fabiani, Mariana Figueiro, Jay Gupta, Ben Hampstead, Marie Hayes, Abhishek Rege, Fiza Singh, Nancy Tuvesson, Shuai Xu. Neurotechnology in Normal Brain Aging, AD, and ADRD April 27, 2020 Table of Contents Executive Summary ............................................................................................................... 1 Meeting Summary ................................................................................................................. 3 Welcome and Opening Remarks .............................................................................................................. 3 Using Non-invasive Sensory Stimulation to Ameliorate Alzheimer’s Disease Pathology and Symptoms 3 Flipping the Switch: How to Use Light to Improve the Lives and Health of Persons with Alzheimer’s Disease and Related Dementias ..............................................................................................................
    [Show full text]
  • Mild Cognitive Impairment (Mci) and Dementia February 2017
    CareCare Process Process Model Model FEBRUARY MONTH 2015 2017 DIAGNOSIS AND MANAGEMENT OF Mild Cognitive Impairment (MCI) and Dementia minor update - 12 / 2020 The Intermountain Cognitive Care Development Team developed this care process model (CPM) to improve the diagnosis and treatment of patients with cognitive impairment across the staging continuum from mild impairment to advanced dementia. It is primarily intended as a tool to assist primary care teams in making the diagnosis of dementia and in providing optimal treatment and support to patients and their loved ones. This CPM is based on existing guidelines, where available, and expert opinion. WHAT’S INSIDE? Why Focus ON DIAGNOSIS AND MANAGEMENT ALGORITHMS OF DEMENTIA? Algorithm 1: Diagnosing Dementia and MCI . 6 • Prevalence, trend, and morbidity. In 2016, one in nine people age 65 and Algorithm 2: Dementia Treatment . .. 11 older (11%) has Alzheimer’s, the most common dementia. By 2050, that Algorithm 3: Driving Assessment . 13 number may nearly triple, and Utah is expected to experience one of the Algorithm 4: Managing Behavioral and greatest increases of any state in the nation.HER,WEU One in three seniors dies with Psychological Symptoms . 14 a diagnosis of some form of dementia.ALZ MCI AND DEMENTIA SCREENING • Costs and burdens of care. In 2016, total payments for healthcare, long-term AND DIAGNOSIS ...............2 care, and hospice were estimated to be $236 billion for people with Alzheimer’s MCI TREATMENT AND CARE ....... HUR and other dementias. Just under half of those costs were borne by Medicare. MANAGEMENT .................8 The emotional stress of dementia caregiving is rated as high or very high by nearly DEMENTIA TREATMENT AND PIN, ALZ 60% of caregivers, about 40% of whom suffer from depression.
    [Show full text]
  • The Three Amnesias
    The Three Amnesias Russell M. Bauer, Ph.D. Department of Clinical and Health Psychology College of Public Health and Health Professions Evelyn F. and William L. McKnight Brain Institute University of Florida PO Box 100165 HSC Gainesville, FL 32610-0165 USA Bauer, R.M. (in press). The Three Amnesias. In J. Morgan and J.E. Ricker (Eds.), Textbook of Clinical Neuropsychology. Philadelphia: Taylor & Francis/Psychology Press. The Three Amnesias - 2 During the past five decades, our understanding of memory and its disorders has increased dramatically. In 1950, very little was known about the localization of brain lesions causing amnesia. Despite a few clues in earlier literature, it came as a complete surprise in the early 1950’s that bilateral medial temporal resection caused amnesia. The importance of the thalamus in memory was hardly suspected until the 1970’s and the basal forebrain was an area virtually unknown to clinicians before the 1980’s. An animal model of the amnesic syndrome was not developed until the 1970’s. The famous case of Henry M. (H.M.), published by Scoville and Milner (1957), marked the beginning of what has been called the “golden age of memory”. Since that time, experimental analyses of amnesic patients, coupled with meticulous clinical description, pathological analysis, and, more recently, structural and functional imaging, has led to a clearer understanding of the nature and characteristics of the human amnesic syndrome. The amnesic syndrome does not affect all kinds of memory, and, conversely, memory disordered patients without full-blown amnesia (e.g., patients with frontal lesions) may have impairment in those cognitive processes that normally support remembering.
    [Show full text]
  • Glutamate Regulation in the Hippocampal Trisynaptic Pathway in Aging and Status Epilepticus
    University of Kentucky UKnowledge University of Kentucky Doctoral Dissertations Graduate School 2009 GLUTAMATE REGULATION IN THE HIPPOCAMPAL TRISYNAPTIC PATHWAY IN AGING AND STATUS EPILEPTICUS Michelle Lee Stephens University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Stephens, Michelle Lee, "GLUTAMATE REGULATION IN THE HIPPOCAMPAL TRISYNAPTIC PATHWAY IN AGING AND STATUS EPILEPTICUS" (2009). University of Kentucky Doctoral Dissertations. 736. https://uknowledge.uky.edu/gradschool_diss/736 This Dissertation is brought to you for free and open access by the Graduate School at UKnowledge. It has been accepted for inclusion in University of Kentucky Doctoral Dissertations by an authorized administrator of UKnowledge. For more information, please contact [email protected]. ABSTRACT OF DISSERTATION Michelle Lee Stephens The Graduate School University of Kentucky 2009 GLUTAMATE REGULATION IN THE HIPPOCAMPAL TRISYNAPTIC PATHWAY IN AGING AND STATUS EPILEPTICUS ABSTRACT OF DISSERTATION A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the College of Medicine at the University of Kentucky By Michelle Lee Stephens Lexington, Kentucky Director: Dr. Greg A. Gerhardt, Professor of Anatomy and Neurobiology Lexington, Kentucky 2009 Copyright © Michelle Lee Stephens 2009 ABSTRACT OF DISSERTATION GLUTAMATE REGULATION IN THE HIPPOCAMPAL TRISYNAPTIC PATHWAY IN AGING AND STATUS EPILEPTICUS A positive correlation exists between increasing age and the incidence of hippocampal-associated dysfunction and disease. Normal L-glutamate neurotransmission is absolutely critical for hippocampal function, while abnormal glutamate neurotransmission has been implicated in many neurodegenerative diseases. Previous studies, overwhelmingly utilizing ex vivo methods, have filled the literature with contradicting reports about hippocampal glutamate regulation during aging.
    [Show full text]
  • LEARNING in SILICON: a NEUROMORPHIC MODEL of the HIPPOCAMPUS John Vernon Arthur a DISSERTATION in Bioengineering Presented to Th
    LEARNING IN SILICON: A NEUROMORPHIC MODEL OF THE HIPPOCAMPUS John Vernon Arthur A DISSERTATION in Bioengineering Presented to the Faculties of the University of Pennsylvania in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy 2006 Kwabena Boahen, Christopher S. Chen, Supervisor of Dissertation Graduate Group Chair COPYRIGHT John Vernon Arthur 2006 Acknowledgements Many people contributed in many ways to my time at Penn. I thank them all. Specifically, I thank my advisor, Kwabena Boahen. He has guided me through many challenges and has provided a constant example of what a researcher should be and can accomplish. Our interactions taught me a great deal and shaped my vision of research, science, and engineering for the better. I thank my committee - Matt Dalva, Leif Finkel, and John Hopfield - who provided advice as well as new insights and different viewpoints that challenged my assumptions, improving my work. I thank those that I had the opportunity to work with - Kareem Zaghloul, Kai Hynna, Brian Taba, Paul Merolla, Bo Wen, John Wittig, Thomas Choi, Rodrigo Alvarez, and Joe Lin - for the time we spent at work and at play. I thank them and many others for their friendship. I thank my family, my parents for exemplifying integrity and work ethic, and my sib- lings for their encouragement. Finally, I thank my wife, Amy, for immeasurable contributions— her enduring support, her constant willingness to help, and her extraordinary tolerance. iii Abstract LEARNING IN SILICON: A NEUROMORPHIC MODEL OF THE HIPPOCAMPUS John Vernon Arthur Supervisor: Kwabena Boahen The human brain is the most complex computing structure in the known universe; it excels at many tasks that digital computers perform poorly, such as learning input patterns and later retreiving them with only a part of the original patterns as input, realizing associa- tive memory.
    [Show full text]
  • Role of Lifestyle in Neuroplasticity and Neurogenesis in an Aging Brain
    Open Access Review Article DOI: 10.7759/cureus.10639 Role of Lifestyle in Neuroplasticity and Neurogenesis in an Aging Brain Reeju Maharjan 1, 2 , Liliana Diaz Bustamante 3 , Kyrillos N. Ghattas 4 , Shahbakht Ilyas 5, 6 , Reham Al-Refai 7 , Safeera Khan 4 1. Neurology, V.N. Karazin Kharkiv National University, Kharkiv, UKR 2. Neurology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA 3. Family Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA 4. Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA 5. Medicine and Surgery, CMH Lahore Medical College and Institute of Dentistry, Lahore, PAK 6. Surgery, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA 7. Pathology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA Corresponding author: Reeju Maharjan, [email protected] Abstract Neuroplasticity is the brain's ability to transform its shape, adapt, and develop a new neuronal connection provided with a new stimulus. The stronger the electrical stimulation, the robust is the transformation. Neurogenesis is a complex process when the new neuronal blast cells present in the dentate gyrus divide in the hippocampus. We collected articles from the past 11 years for review, using the Medical Subject Headings (MeSH) strategy from PubMed. Quality appraisal was done for each research article using various assessment tools. A total of 24 articles were chosen, applying all the mentioned inclusion and exclusion criteria and reviewed. The reviewed studies emphasized that modifiable lifestyle factors such as diet and exercise should be implemented as an intervention in the elderly for healthy aging of the brain, as the world's aging population is going to be increased, leading to the expansion of health care and cost.
    [Show full text]
  • Implications of Aging Neuronal Gain Control on Cognition
    Available online at www.sciencedirect.com ScienceDirect Neuromodulation and aging: implications of aging neuronal gain control on cognition 1,2 3,4 Shu-Chen Li and Anna Rieckmann The efficacy of various transmitter systems declines with 30-year gain in physical health is, however, not necess- advancing age. Of particular interest, various pre-synaptic and arily accompanied by cognitive fitness and mental well- post-synaptic components of the dopaminergic system being into old age. Faced with the rapid growth of aging change across the human lifespan; impairments in these populations worldwide and an ever-expanding prevalence components play important roles in cognitive deficits of dementia, understanding brain aging and aging-related commonly observed in the elderly. Here, we review evidence cognitive declines has become a key challenge for neuro- from recent multimodal neuroimaging, pharmacological and science and psychology in the 21st century. genetic studies that have provided new insights for the associations among dopamine functions, aging, functional Brain aging is characterized by multiple neurobiological brain activations and behavioral performance across key changes including losses of white matter integrity, cortical cognitive functions, ranging from working memory and thickness and grey matter volumes, metabolic activity, episodic memory to goal-directed learning and decision and neurotransmitter functions (e.g. see [4 ] for an over- making. Specifically, we discuss these empirical findings in the view). The focus of the current review will be on aging- context of an established neurocomputational theory of aging related declines in neurotransmitter functions and the neuronal gain control. We also highlight gaps in the current associated implications for cognitive functioning.
    [Show full text]
  • A Neural Mechanism for Capnotaxis in the Naked Mole-Rat
    City University of New York (CUNY) CUNY Academic Works All Dissertations, Theses, and Capstone Projects Dissertations, Theses, and Capstone Projects 2-2020 A Neural Mechanism for Capnotaxis in the Naked Mole-Rat Michael Zions The Graduate Center, City University of New York How does access to this work benefit ou?y Let us know! More information about this work at: https://academicworks.cuny.edu/gc_etds/3555 Discover additional works at: https://academicworks.cuny.edu This work is made publicly available by the City University of New York (CUNY). Contact: [email protected] A NEURAL MECHANISM FOR CAPNOTAXIS IN THE NAKED MOLE-RAT By MICHAEL ZIONS A dissertation submitted to the Graduate Faculty in Biology in partial fulfillment of the requirements for the degree of Doctor of Philosophy, The City University of New York 2020 © 2020 MICHAEL ZIONS All Rights Reserved ii A NEURAL MECHANISM FOR CAPNOTAXIS IN THE NAKED MOLE-RAT By Michael Zions This manuscript has been read and accepted for the Graduate Faculty in Biology in satisfaction of the dissertation requirements for the degree of Doctor of Philosophy. Date Dan P. McCloskey, Ph.D. (College of Staten Island) Chair of Examining Committee Date Christine Li, Ph.D. Acting Executive Officer Graduate Center/CUNY Program in Biology Supervisory Committee Dr. Abdeslem El Idrissi, College of Staten Island, City University of New York Dr. Jeffrey Goodman, Dept. of Developmental Biology, Institute for Basic Research Dr. Jonathan Levitt, City College, City University of New York Dr. Kai Kaila, Laboratory of Neurobiology, Neuroscience Center, University of Helsinki THE CITY UNIVERSITY OF NEW YORK iii ABSTRACT A Neural Mechanism for Capnotaxis in the Naked Mole-Rat by Michael Zions Advisor: Dan P.
    [Show full text]
  • Somatostatin-Positive Interneurons in the Dentate Gyrus of Mice Provide
    RESEARCH ARTICLE Somatostatin-positive interneurons in the dentate gyrus of mice provide local- and long-range septal synaptic inhibition Mei Yuan1,2†, Thomas Meyer1†, Christoph Benkowitz1, Shakuntala Savanthrapadian1, Laura Ansel-Bollepalli3, Angelica Foggetti3, Peer Wulff3, Pepe Alcami1, Claudio Elgueta1, Marlene Bartos1* 1Systemic and Cellular Neurophysiology, Institute for Physiology I, University of Freiburg, Freiburg, Germany; 2Faculty for Biology, University of Freiburg, Freiburg, Germany; 3Institute for Physiology, University of Kiel, Kiel, Germany Abstract Somatostatin-expressing-interneurons (SOMIs) in the dentate gyrus (DG) control formation of granule cell (GC) assemblies during memory acquisition. Hilar-perforant-path- associated interneurons (HIPP cells) have been considered to be synonymous for DG-SOMIs. Deviating from this assumption, we show two functionally contrasting DG-SOMI-types. The classical feedback-inhibitory HIPPs distribute axon fibers in the molecular layer. They are engaged by converging GC-inputs and provide dendritic inhibition to the DG circuitry. In contrast, SOMIs with axon in the hilus, termed hilar interneurons (HILs), provide perisomatic inhibition onto GABAergic cells in the DG and project to the medial septum. Repetitive activation of glutamatergic inputs onto HIPP cells induces long-lasting-depression (LTD) of synaptic transmission but long-term- potentiation (LTP) of synaptic signals in HIL cells. Thus, LTD in HIPPs may assist flow of spatial information from the entorhinal cortex to the DG, whereas LTP in HILs may facilitate the temporal coordination of GCs with activity patterns governed by the medial septum. *For correspondence: marlene. DOI: 10.7554/eLife.21105.001 [email protected]. de †These authors contributed equally to this work Introduction Competing interest: See The DG is situated between the entorhinal cortex and the CA3 area of the hippocampus, forming page 20 the first stage of the classical trisynaptic circuit (Andersen et al., 1971; Eichenbaum, 1993; Lis- man, 1999).
    [Show full text]
  • The Aging Brain and Neuroplasticity
    POWER OF POSITIVE AGING NEUROPLASTICITY AND THE AGING BRAIN Worlds First Senior Moment . QUIZ • Loss of memory is a normal part of aging • The brain can form new connections throughout life • We can predict which individuals with memory complaints will progress to Alzheimer’s disease dementia THERE WILL BE A LOT OF AGING BRAINS • By 2029, 20% of population over 65 • 65 y/o will live, on average, 20 more years • Effect of 10-25% reduction in 7 risk factors may prevent up to 500,000 cases of AD IS MEMORY LOSS A NORMAL PART OF AGING MEMORY • Multiple sub-systems: Episodic (personally relevant events/episodes) Working (manipulate learned info) Semantic (knowledge of facts, meaning of words) Procedural (performance of skills) • Can run independently MEMORY PROCESS Sensations Sensations Sensations Sensations Immediate Memory 1. encoding Short Term Memory 3. Retrieval 2. storage Long Term Memory WHAT’S NORMAL, WHAT’S NOT? Normal Aging Cognitive Function Years NORMAL COGNITIVE AGING • Slowing of central processing • Mild changes in memory • Other cognitive abilities relatively preserved NORMAL AGING: COGNITIVE CHANGES 50 YO +20% 80 YO 20 YO -20% -40% -60% Vocabulary Mental Verbal Fluency Math NORMAL AGING: COGNITIVE CHANGES 50 YO +20% 80 YO 20 YO -20% -40% -60% Selective Mental Visual- Attention Flexibility Construction AGE-RELATED MEMORY/COGNITIVE CHANGES • Few changes: • Declines: • Crystallized Intelligence • Sensory Memory • Procedural Memory • Short-term Memory • Complex/Selective Attention • Long-term Memory • Executive Skills • Auditory
    [Show full text]