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Identification of Neural Markers Accompanying Memory
Identification of Neural Markers Accompanying Memory
Identification of Neural Markers Accompanying Memory
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Identification of Neural Markers Accompanying Memory

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Identification of Neural Markers Accompanying Memory is a fresh and novel volume of memory study, providing up-to-date and comprehensive information for both students and researchers focused on the identification of neural markers accompanying memory. Contributions by experts in specific areas of memory study provide background on and definitions of memory, memory alterations, and the brain areas involved in memory and its related processes, such as consolidation, retrieval, forgetting, amnesia, and antiamnesiac effects. With coverage of the principal neurotransmitters related to memory, brain disorders presenting memory alterations, and available treatments—and with discussion of neural markers as new targets for the treatment of memory alterations—Identification of Neural Markers Accompanying Memory is a necessary and timely work for researchers in this growing field.

  • Discusses the alterations of memory in diverse diseases
  • Includes coverage from a basic introduction of memory investigation
  • Reviews brain areas and neurotransmitters involved in memory
  • Discusses behavioral models of memory
  • Contains novel insights into the complexity of signaling and memory
  • Includes the neuropharmacological and neurobiological bases of memory
LanguageEnglish
Release dateNov 23, 2013
ISBN9780124167117
Identification of Neural Markers Accompanying Memory

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    Identification of Neural Markers Accompanying Memory - Alfredo Meneses

    1

    Introduction

    Alfredo Meneses,    Department of Pharmacobiology, CINVESTAV, México

    Contributions of age-related changes in neuromodulatory systems to cognitive decline, but also the contribution of interactions between neurotransmission systems and their transporters to the learning and memory deficits associated with aging and AD and forgetting. Excellent, fresh, and new advances are included. Also, the contribution of pharmacology to research on the mechanisms of memory formation is one of the major focus.

    Keywords

    Memory; dysfunctional memory; neurotransmitters systems

    Neurotransmitters and Memory: Introduction

    Memory is a basic function of the brain and fundamental in our life. Memory may be defined according to its content, in relation to time and its neurobiological basis: in the former case, as declarative/explicit or nondeclarative/implicit memory, and regarding time, as short-term memory (STM) or working and long-term memory (LTM) (Davis and Squire, 1984; Izquierdo et al., 1999, 2006); the latter depends on protein and mRNA synthesis (Meneses et al., 2011). Considering that memory is a field of scientific investigation in constant expansion, hence in this book the aim is offering a brief and introductory overview for students of the area, using relevant and (and when is possible) recent references. Diverse brain areas (Squire and Zola, 1996; Eichenbaum, 2013), neurotransmitters (see below), and cell signaling have been associated to memory (Vianna et al., 2000) and its alterations.

    Firstly, extensive evidence indicates that disruption of cholinergic function is characteristic of aging and Alzheimer’s disease (AD), and experimental manipulation of the cholinergic system in laboratory animals suggests age-related cholinergic dysfunction may play an important role in cognitive deterioration associated with aging and AD (Decker and McGaugh, 2004; McGaugh, 1989; Myhrer, 2003). Recent investigation, however, suggests that cholinergic dysfunction does not provide a complete account of age-related cognitive deficits and that age-related changes in cholinergic function typically occur within the context of changes in several other neuromodulatory systems. Interactions between the cholinergic system and several of other neurotransmitters and neuromodulators (including norepinephrine, dopamine, serotonin, GABA, opioid peptides, galanin, substance P, and angiotensin II) may be important in learning and memory (Decker and McGaugh, 2004; Reiss et al., 2009). It is important to consider not only the independent contributions of age-related changes in neuromodulatory systems to cognitive decline, but also the contribution of interactions between neurotransmission systems to the learning and memory deficits associated with aging and AD (Decker and McGaugh, 2004).

    In perspective, if receptors for all agents (e.g., hormones, trophic factors odorants, peptides) in addition to the transmitters were counted, a total of 1000 would not be surprising (Cooper et al., 2003). Before this abundance of neurotransmitters, then, among the neurotransmitters mentioned in this chapter, we are including the cholinergic (Bentley et al., 2011; Graef et al., 2011), glutamatergic (Piers et al., 2012; chapter 3 this volume), GABAergic (Reiss et al., 2009; chapter 4 this volume), dopaminergic (Reiss et al., 2009; chapter 5 this volume), and serotonergic (serotonin, 5-hydroxytryptamine or 5-HT) (Altman and Normile, 1988; Ogren, 1985; Rodríguez et al., 2012; see below). Importantly, the behavioral endophenotypes had become an important tool (chapter 6 this volume). An excellent, fresh, and new advance is about a role for learning and memory in the expression of an innate behavior (chapter 9 this volume). Of course, protein synthesis and memory had become an important subject (chapter 7 this volume).

    As a detailed description of the neurotransmission systems included herein is beyond the present work, then a shallow overview is provided. An excellent atlas about neuroactive substances, their projections and receptors is available (Tohyama et al., 1998); hence, in this work the contribution of pharmacology to research on the mechanisms of memory formation (McGaugh and Izquierdo, 2000) is one of the major focus. Certainly, the transporters of neurotransmission systems play a crucial function in the regulation of intra-synaptic concentrations and play an important role in memory formation, amnesia, anti-amnesic effects, and forgetting (see e.g., Tellez et al., 2012a,b). Likewise, hippocampal neurogenesis and forgetting are important (Frankland et al., 2013). Finally, the diabetes case (chapter 10 this volume) allows illustrating the variety of memory disorders. The basic elements of signal transduction pathways are provided (chapter 8 this volume).

    References

    1. Altman HJ, Normile HJ. What is the nature of the role of the serotonergic nervous system in learning and memory: prospects for development of an effective treatment strategy for senile dementia. Neurobiol Aging. 1988;9(5–6):627–638.

    2. Bentley P, Driver J, Dolan RJ. Cholinergic modulation of cognition: insights from human pharmacological functional neuroimaging. Prog Neurobiol. 2011;94(4):360–388.

    3. Cooper JR, Bloom FE, Roth RH. The Biochemical Basis of Neuropharmacology New York, NY: Oxford University Press; 2003.

    4. Davis HP, Squire LR. Protein synthesis and memory: a review. Psychol Bull. 1984;96(3):518–559.

    5. Decker MW, McGaugh JL. The role of interactions between the cholinergic system and other neuromodulatory systems in learning and memory. Synapse. 2004;7(2):151–168.

    6. Eichenbaum H. What H.M taught us. J Cogn Neurosci. 2013;25(1):14–21.

    7. Frankland PW, Köhler S, Josselyn SA. Hippocampal neurogenesis and forgetting. Trends Neurosci. 2013;36(9):497–503.

    8. Graef S, Schönknecht P, Sabri O, Hegerl U. Cholinergic receptor subtypes and their role in cognition, emotion, and vigilance control: an overview of preclinical and clinical findings. Psychopharmacology (Berl.). 2011;215(2):205–229.

    9. Izquierdo I, Medina JH, Vianna MR, Izquierdo LA, Barros DM. Separate mechanisms for short- and long-term memory. Behav Brain Res. 1999;103(1):1–11.

    10. Izquierdo I, Bevilaqua LR, Rossato JI, Bonini JS, Medina JH, Cammarota M. Different molecular cascades in different sites of the brain control memory consolidation. Trends Neurosci. 2006;29(9):496–505.

    11. McGaugh JL. Dissociating learning and performance: drug and hormone enhancement of memory storage. Brain Res Bull. 1989;23(4–5):339–345.

    12. McGaugh JL, Izquierdo I. The contribution of pharmacology to research on the mechanisms of memory formation. Trends Pharmacol Sci. 2000;21(6):208–210.

    13. Meneses A, Pérez-García G, Ponce-Lopez T, Castillo C. 5-HT6 receptor memory and amnesia: behavioral pharmacology—learning and memory processes. Int Rev Neurobiol. 2011;96:27–47.

    14. Myhrer T. Neurotransmitter systems involved in learning and memory in the rat: a meta-analysis based on studies of four behavioral tasks. Brain Res Rev. 2003;41:268–287.

    15. Ogren SO. Evidence for a role of brain serotonergic neurotransmission in avoidance learning. Acta Physiol Scand Suppl. 1985;544:1–71.

    16. Piers TM, Kim DH, Kim BC, Regan P, Whitcomb DJ, Cho K. Translational concepts of mGluR5 in synaptic diseases of the brain. Front Pharmacol. 2012;3:199.

    17. Reis HJ, Guatimosim C, Paquet M, et al. Neuro-transmitters in the central nervous system & their implication in learning and memory processes. Curr Med Chem. 2009;16(7):796–840.

    18. Rodríguez JJ, Noristani HN, Verkhratsky A. The serotonergic system in ageing and Alzheimer’s disease. Prog Neurobiol. 2012;99:15–41.

    19. Squire LR, Zola SM. Structure and function of declarative and nondeclarative memory systems. Proc Natl Acad Sci USA. 1996;93(24):13515–13522.

    20. Tellez R, Gómez-Víquez L, Meneses A. GABA, glutamate, dopamine and serotonin transporters expression on memory formation and amnesia. Neurobiol Learn Mem. 2012a;97(2):189–201.

    21. Tellez R, Gómez-Viquez L, Liy-Salmeron G, Meneses A. GABA, glutamate, dopamine and serotonin transporters expression on forgetting. Neurobiol Learn Mem. 2012b;98(1):66–77.

    22. Tohyama M, Takatsuji K, Kantha SS, eds. Atlas of Neuroactive Substances and Their Receptors in the Rat. Oxford: Oxford University Press; 1998.

    23. Vianna MR, Izquierdo LA, Barros DM, Walz R, Medina JH, Izquierdo I. Short- and long-term memory: differential involvement of neurotransmitter systems and signal transduction cascades. An Acad Bras Cienc. 2000;72(3):353–364.

    2

    Neurotransmitters and Memory

    Cholinergic, Glutamatergic, GaBAergic, Dopaminergic, Serotonergic, Signaling, and Memory

    Alfredo Meneses,    Department of Pharmacobiology, CINVESTAV, México

    Certainly, beyond the implication of cholinergic system in memory and therapeutic applications, the muscarinic antagonist scopolamine had been a remarkable amnesic agent. In addition, therapeutic options for AD are currently limited to symptomatic treatment that only provides modest and temporary maintenance of cognitive and memory functions, without altering disease progression. Neurotransmitters like glutamate, GABA, dopamine and serotonin seem to be involved in memory and its alterations; hence some aspects and data are summarized. Importantly, 5-HT systems and neurobiological markers related to memory systems are revised. Likewise, protocols of training/testing, memory tasks and drugs used are briefly discussed. Importantly, determination if drugs, age and/or memory alone alter receptor expression and/or signal cascades is very important. Brain areas, neurotransmitters systems, drugs together with cognitive and behavioral demand of memory tasks, and protocols of training are highlighted. Molecular signaling is key field of scientific investigation; particularly, as the study of the molecular bases of memory has been become a field of the major scientific interest, hence, in the following lines some aspects are mentioned. Moreover, quest for memory enhancement is an important investigation area; considering that the global population is increasingly aging. Finally, in addition to pharmacological approaches, there are a number of behavioral manipulations that have been found to be effective in promoting memory.

    Keywords

    Memory; amnesia; forgetting; memory disorders; neurotransmitters; acetylcholine; GABA; glutamate; dopamine; serotonin; behavioral models of memory; signaling; tentative treatments for memory dysfunctions

    Neurotransmitters and Memory

    Cholinergic

    Terry and Buccafusco in 2003 revised the cholinergic hypothesis about memory, which was initially presented over 20 years ago, indicating that a dysfunction of acetylcholine containing neurons in the brain contributes substantially to the cognitive decline observed in those with advanced age and Alzheimer’s disease (AD). This premise has since served as the basis for the majority of treatment strategies and drug development approaches for AD to date (Terry and Buccafusco, 2003; see also Bentley et al., 2011; Cummings et al., 2012; Decker and McGaugh, 2004). Studies of the brains of patients who had mild cognitive impairment (MCI) or early stage AD in which choline acetyltransferase and/or acetylcholinesterase activity was unaffected (or even upregulated) have, however, led some to challenge the validity of the hypothesis as well as the rationale for using cholinomimetics to treat the disorder, particularly in the earlier stages (Terry and Buccafusco, 2003). These challenges primarily are based on assays of postmortem enzyme activity, which should be taken in perspective and evaluated within the wide range of cholinergic abnormalities known to exist in both aging and AD (e.g., Zhang et al., 2012; Zhou et al., 2012). In addition, the results of both postmortem and antemortem studies in aged humans and AD patients, as well as preclinical animal experimentation, suggest that a host of cholinergic abnormalities including alterations in choline transport, acetylcholine release, nicotinic and muscarinic receptor expression, neurotrophin support, and perhaps axonal transport may all contribute to cognitive abnormalities in aging and AD (Terry and Buccafusco, 2003; see also Graef et al., 2011; Martyn et al., 2012) as well as other neurotransmitter systems. Cholinergic abnormalities may also contribute to noncognitive behavioral abnormalities as well as the deposition of toxic neuritic plaques in AD. Therefore, cholinergic-based strategies will likely remain valid approaches to rational drug development for the treatment of AD and other forms of dementia (Terry and Buccafusco, 2003). Focus on the cholinergic system in aging and neuronal degeneration reveals that the basal forebrain cholinergic complex comprising medial septum, horizontal and vertical diagonal band of Broca, and nucleus basalis of Meynert provides the mayor cholinergic projections to the cerebral cortex and hippocampus (Schliebs and Arendt, 2011). The cholinergic neurons of this complex have been assumed to undergo moderate degenerative changes during aging, resulting in cholinergic hypofunction that has been related to the progressing memory deficits with aging. However, the previous view of significant cholinergic cell loss during aging has been challenged (Schliebs and Arendt, 2011). Neuronal cell loss was found predominantly in pathological aging, such as AD, while normal aging is accompanied by a gradual loss of cholinergic function caused by dendritic, synaptic, and axonal degeneration as well as a decrease in trophic support (Schliebs and Arendt, 2011; see also Tremblay et al., 2010). As a consequence, decrements in gene expression, impairments in intracellular signaling, and cytoskeletal transport may mediate cholinergic cell atrophy, which finally leads to the known age-related functional decline in the brain including aging-associated cognitive impairments (Schliebs and Arendt, 2011). However, in pathological situations associated with cognitive deficits, such as Parkinsons’s disease, Down syndrome, progressive supranuclear palsy, Creutzfeldt–Jakob disease, Korsakoff’s syndrome, traumatic brain injury, significant degenerations of basal forebrain cholinergic cells, have been observed. In presenile (early onset), and in the advanced stages of late-onset AD, a severe loss of cortical cholinergic innervation has extensively been documented. In contrast, in patients with MCI (a prodromal stage of AD), and early forms of AD, apparently no cholinergic neurodegeneration but a loss of cholinergic function occurs (Schliebs and Arendt, 2011). In particular imbalances in the expression of NGF, its precursor proNGF, the high and low NGF receptors, trkA and p75NTR, respectively, changes in acetylcholine release, high-affinity choline uptake, as well as alterations in muscarinic and nicotinic acetylcholine receptor expression, may contribute to the cholinergic dysfunction (Reiss et al., 2009; Schliebs and Arendt, 2011). These observations support the suggestion of a key role of the cholinergic system in the functional processes that lead to AD. Malfunction of the cholinergic system may be tackled pharmacologically by intervening in cholinergic as well as neurotrophic signaling cascades that have been shown to ameliorate the cholinergic deficit at early stages of the disease and slow down the progression (Schliebs and Arendt, 2011). However, in contrast to many other disorders demential ones, in AD the cholinergic dysfunctions are accompanied by the occurrence of two major histopathological hallmarks such as β-amyloid plaques and neurofibrillary tangles, provoking the question whether they play a particular role in inducing or mediating cholinergic dysfunction in AD (Schliebs and Arendt, 2011). Indeed, there is abundant evidence that β-amyloid may trigger cholinergic dysfunction through action on α7-nicotinic acetylcholine receptors, affecting NGF signaling, mediating tau phosphorylation, interacting with acetylcholinesterase, and specifically affecting the proteome in cholinergic neurons (Schliebs and Arendt, 2011). Therefore, an early onset of an anti-β-amyloid strategy may additionally be potential in preventing aging-associated cholinergic deficits and cognitive impairments (Schliebs and Arendt, 2011). Herein, it is important to highlight that AD likely represents the most known psychiatry disorder where memory is (progressively) impaired; however, others (e.g., depression, Parkinson’s disease; see Millan et al., 2012) also present memory deficits. Certainly, beyond the implication of cholinergic system in memory and therapeutic applications, the muscarinic antagonist scopolamine had been a remarkable amnesic agent (Klinkenberg and Blokland,

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