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https://www.readbyqxmd.com/read/28213444/the-dendrites-of-ca2-and-ca1-pyramidal-neurons-differentially-regulate-information-flow-in-the-cortico-hippocampal-circuit
#1
Kalyan V Srinivas, Eric W Buss, Qian Sun, Bina Santoro, Hiroto Takahashi, Daniel A Nicholson, Steven A Siegelbaum
The impact of a given neuronal pathway depends on the number of synapses it makes with its postsynaptic target, the strength of each individual synapse and the integrative properties of the postsynaptic dendrites. Here we explore the cellular and synaptic mechanisms responsible for the differential excitatory drive from the entorhinal cortical pathway onto mouse CA2 compared to CA1 pyramidal neurons (PNs). Although both types of neurons receive direct input from entorhinal cortex onto their distal dendrites, these inputs produce a 5-6 fold larger excitatory postsynaptic potential (EPSP) at the soma of CA2 compared to CA1 PNs, which is sufficient to drive action potential output from CA2 but not CA1...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28209738/optogenetic-low-frequency-stimulation-of-specific-neuronal-populations-abates-ictogenesis
#2
Zahra Shiri, Maxime Lévesque, Guillaume Etter, Frédéric Manseau, Sylvain Williams, Massimo Avoli
Despite many advances made in understanding the pathophysiology of epileptic disorders, seizures remain poorly controlled in approximately one third of mesial temporal lobe epilepsy patients. Here, we established the efficacy of cell type-specific low-frequency stimulation (LFS) in controlling ictogenesis in the mouse entorhinal cortex (EC) in an in vitro brain slice preparation. Specifically, we used 1 Hz optogenetic stimulation of Ca(2+)/calmodulin-dependent protein kinase II-positive principal cells as well as of parvalbumin- or somatostatin-positive interneurons to study the effects of such repetitive activation on epileptiform discharges induced by 4-aminopyridine...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28205565/entorhinal-cortex-dysfunction-can-be-rescued-by-inhibition-of-microglial-rage-in-an-alzheimer-s-disease-mouse-model
#3
Chiara Criscuolo, Veronica Fontebasso, Silvia Middei, Martina Stazi, Martine Ammassari-Teule, Shirley ShiDu Yan, Nicola Origlia
The Entorhinal cortex (EC) has been implicated in the early stages of Alzheimer's disease (AD). In particular, spreading of neuronal dysfunction within the EC-Hippocampal network has been suggested. We have investigated the time course of EC dysfunction in the AD mouse model carrying human mutation of amyloid precursor protein (mhAPP) expressing human Aβ. We found that in mhAPP mice plasticity impairment is first observed in EC superficial layer and further affected with time. A selective impairment of LTP was observed in layer II horizontal connections of EC slices from 2 month old mhAPP mice, whereas at later stage of neurodegeneration (6 month) basal synaptic transmission and LTD were also affected...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196395/spread-of-tau-down-neural-circuits-precedes-synapse-and-neuronal-loss-in-the-rtgtauec-mouse-model-of-early-alzheimer-s-disease
#4
Eleanor K Pickett, Christopher M Henstridge, Elizabeth Allison, Rose Pitstick, Amy Pooler, Susanne Wegmann, George Carlson, Bradley T Hyman, Tara L Spires-Jones
Synaptic dysfunction and loss is the strongest pathological correlate of cognitive decline in Alzheimer's disease (AD) with increasing evidence implicating neuropathological tau protein in this process. Despite the knowledge that tau spreads through defined synaptic circuits, it is currently unknown whether synapse loss occurs before the accumulation of tau or as a consequence. To address this, we have used array tomography to examine an rTgTauEC mouse model expressing a P301L human tau transgene and a transgene labelling cytoplasm red (tdTomato) and presynaptic terminals green (Synaptophysin-EGFP)...
February 14, 2017: Synapse
https://www.readbyqxmd.com/read/28193301/hippocampal-subregion-volume-changes-associated-with-antipsychotic-treatment-in-first-episode-psychosis
#5
K Rhindress, D G Robinson, J A Gallego, R Wellington, A K Malhotra, P R Szeszko
BACKGROUND: Hippocampal dysfunction is considered central to many neurobiological models of schizophrenia, yet there are few longitudinal in vivo neuroimaging studies that have investigated the relationship between antipsychotic treatment and morphologic changes within specific hippocampal subregions among patients with psychosis. METHOD: A total of 29 patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure received structural neuroimaging examinations at illness onset and then following 12 weeks of treatment with either risperidone or aripiprazole in a double-blind randomized clinical trial...
February 14, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/28192082/endocannabinoid-dependent-protection-against-kainic-acid-induced-long-term-alteration-of-brain-oscillations-in-guinea-pigs
#6
Liubov Shubina, Rubin Aliev, Valentina Kitchigina
Changes in rhythmic activity can serve as early biomarkers of pathological alterations, but it remains unclear how different types of rhythmic activity are altered during neurodegenerative processes. Glutamatergic neurotoxicity, evoked by kainic acid (KA), causes hyperexcitation and acute seizures that result in delayed brain damage. We employed wide frequency range (0.1-300 Hz) local field potential recordings in guinea pigs to study the oscillatory activity of the hippocampus, entorhinal cortex, medial septum, and amygdala in healthy animals for three months after KA introduction...
February 9, 2017: Brain Research
https://www.readbyqxmd.com/read/28188663/histamine-facilitates-gabaergic-transmission-in-the-rat-entorhinal-cortex-roles-of-h1-and-h2-receptors-na-permeable-cation-channels-and-inward-rectifier-k-channels
#7
Nicholas I Cilz, Saobo Lei
In the brain, histamine (HA) serves as a neuromodulator and a neurotransmitter released from the tuberomammillary nucleus (TMN). HA is involved in wakefulness, thermoregulation, energy homeostasis, nociception and learning and memory. The medial entorhinal cortex (MEC) receives inputs from the TMN and expresses HA receptors (H1 , H2 , and H3 ). We investigated the effects of HA on GABAergic transmission in the MEC and found that HA significantly increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) with an EC50 of 1...
February 11, 2017: Hippocampus
https://www.readbyqxmd.com/read/28183529/hippocampal-thinning-linked-to-longer-tomm40-poly-t-variant-lengths-in-the-absence-of-the-apoe-%C3%AE%C2%B54-variant
#8
Alison C Burggren, Zanjbeel Mahmood, Theresa M Harrison, Prabha Siddarth, Karen Miller, Gary Small, David A Merrill, Susan Bookheimer
INTRODUCTION: The translocase of outer mitochondrial membrane 40 (TOMM40), which lies in linkage disequilibrium with apolipoprotein E (APOE), has received attention more recently as a promising gene in Alzheimer's disease (AD) risk. TOMM40 influences AD pathology through mitochondrial neurotoxicity, and the medial temporal lobe (MTL) is the most likely brain region for identifying early manifestations of AD-related morphology changes. METHODS: In this study, we examined the effects of TOMM40 using high-resolution magnetic resonance imaging in 65 healthy, older subjects with and without the APOE ε4 AD-risk variant...
February 6, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28174077/separation-or-binding-role-of-the-dentate-gyrus-in-hippocampal-mnemonic-processing
#9
REVIEW
Jong Won Lee, Min Whan Jung
As a major component of the hippocampal trisynaptic circuit, the dentate gyrus (DG) relays inputs from the entorhinal cortex to the CA3 subregion. Although the anatomy of the DG is well characterized, its contribution to hippocampal mnemonic processing is still unclear. A currently popular theory proposes that the primary function of the DG is to orthogonalize incoming input patterns into non-overlapping patterns (pattern separation). We critically review the available data and conclude that the theoretical support and empirical evidence for this theory are not strong...
February 4, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28169828/functional-double-dissociation-within-the-entorhinal-cortex-for-visual-scene-dependent-choice-behavior
#10
Seung-Woo Yoo, Inah Lee
How visual scene memory is processed differentially by the upstream structures of the hippocampus is largely unknown. We sought to dissociate functionally the lateral and medial subdivisions of the entorhinal cortex (LEC and MEC, respectively) in visual scene-dependent tasks by temporarily inactivating the LEC and MEC in the same rat. When the rat made spatial choices in a T-maze using visual scenes displayed on LCD screens, the inactivation of the MEC but not the LEC produced severe deficits in performance...
February 7, 2017: ELife
https://www.readbyqxmd.com/read/28169581/gray-matter-trophism-cognitive-impairment-and-depression-in-patients-with-multiple-sclerosis
#11
Emanuele Pravatà, Maria A Rocca, Paola Valsasina, Gianna C Riccitelli, Claudio Gobbi, Giancarlo Comi, Andrea Falini, Massimo Filippi
BACKGROUND: Cognitive impairment and depression frequently affects patients with multiple sclerosis (MS). However, the relationship between the occurrence of depression and cognitive impairment and the development of cortical atrophy has not been fully elucidated yet. OBJECTIVES: To investigate the association of cortical and deep gray matter (GM) volume with depression and cognitive impairment in MS. METHODS: Three-dimensional (3D) T1-weighted scans were obtained from 126 MS patients and 59 matched healthy controls...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28167117/protection-against-alcohol-induced-neuronal-and-cognitive-damage-by-the-ppar%C3%AE-receptor-agonist-pioglitazone
#12
Andrea Cippitelli, Esi Domi, Massimo Ubaldi, James C Douglas, Hong Wu Li, Gregory Demopulos, George Gaitanaris, Marisa Roberto, Paul D Drew, Cynthia J M Kane, Roberto Ciccocioppo
Binge alcohol drinking has emerged as a typical phenomenon in young people. This pattern of drinking, repeatedly leading to extremely high blood and brain alcohol levels and intoxication is associated with severe risks of neurodegeneration and cognitive damage. Mechanisms involved in excitotoxicity and neuroinflammation are pivotal elements in alcohol-induced neurotoxicity. Evidence has demonstrated that PPARγ receptor activation shows anti-inflammatory and neuroprotective properties. Here we examine whether treatment with the PPARγ agonist pioglitazone is beneficial in counteracting neurodegeneration, neuroinflammation and cognitive damage produced by binge alcohol intoxication...
February 3, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28164769/change-in-insr-apba2-and-ide-gene-expressions-in-brains-of-alzheimer%C3%A2-s-disease-patients
#13
Isabela Bazzo Da Costa, Roger Willian De Labio, Lucas Trevizani Rasmussen, Gustavo Arruda Viani, Elizabeth Chen, João Villares, Gustavo Turecki, Marília De Arruda Cardoso Smith, Spencer L M Payão
Alzheimer's disease (AD) is defined as a progressive and irreversible neurodegenerative disorder, the onset of which is mainly characterized by decreased cognition, memory loss, and mental confusion. This study sought to quantify mRNA expression of the APBA2, INSR and IDE genes in brain samples from both patients with AD and controls. We investigated the mRNA expression of the APBA2, INSR and IDE genes in 150 RNA samples from the entorhinal cortex, the auditory cortex, and the hippocampus of individuals with AD and elderly controls using real time PCR...
February 2, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28161726/medial-entorhinal-cortex-and-medial-septum-contribute-to-self-motion-based-linear-distance-estimation
#14
Pierre-Yves Jacob, Marta Gordillo-Salas, Justine Facchini, Bruno Poucet, Etienne Save, Francesca Sargolini
Path integration is a navigation strategy that requires animals to integrate self-movements during exploration to determine their position in space. The medial entorhinal cortex (MEC) has been suggested to play a pivotal role in this process. Grid cells, head-direction cells, border cells as well as speed cells within the MEC collectively provide a dynamic representation of the animal position in space based on the integration of self-movements. All these cells are strongly modulated by theta oscillations, thus suggesting that theta rhythmicity in the MEC may be essential for integrating and coordinating self-movement information during navigation...
February 4, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28154241/stellate-cells-drive-maturation-of-the-entorhinal-hippocampal-circuit
#15
Flavio Donato, R Irene Jacobsen, May-Britt Moser, Edvard I Moser
The neural representation of space relies on a network of entorhinal-hippocampal cell types with firing patterns tuned to different abstract features of the environment. To determine how this network is set up during early postnatal development, we monitored markers of structural maturation in developing mice, both in naïve animals and after temporally restricted pharmacogenetic silencing of specific cell populations. We found that entorhinal stellate cells provide an activity-dependent instructive signal that drives maturation sequentially and unidirectionally through the intrinsic circuits of the entorhinal-hippocampal network The findings raise the possibility that a small number of autonomously developing neuronal populations operate as intrinsic drivers of maturation across widespread regions of cortex...
February 2, 2017: Science
https://www.readbyqxmd.com/read/28138510/tau-pet-uptake-regional-variation-in-average-suvr-and-impact-of-amyloid-deposition
#16
Prashanthi Vemuri, Val J Lowe, David S Knopman, Matthew L Senjem, Bradley J Kemp, Christopher G Schwarz, Scott A Przybelski, Mary M Machulda, Ronald C Petersen, Clifford R Jack
INTRODUCTION: Tau-positron emission tomography (PET) imaging with AV1451 is sensitive to Alzheimer disease (AD)-related tau deposition in the brain. We (1) examined regional variation of average tau-PET standardized uptake value ratios (SUVRs) in a young normal population (30-49 years) and corrected for the regional variability and (2) tested if the standardized values (z-scores) scaled appropriately to capture regional Alzheimer-specific (i.e., amyloid sensitive) tau-PET changes in individuals aged 50+ years...
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/28118842/microglial-derived-mirna-let-7-and-hmgb1-contribute-to-ethanol-induced-neurotoxicity-via-tlr7
#17
Leon G Coleman, Jian Zou, Fulton T Crews
BACKGROUND: Toll-like receptor (TLR) signaling is emerging as an important component of neurodegeneration. TLR7 senses viral RNA and certain endogenous miRNAs to initiate innate immune responses leading to neurodegeneration. Alcoholism is associated with hippocampal degeneration, with preclinical studies linking ethanol-induced neurodegeneration with central innate immune induction and TLR activation. The endogenous miRNA let-7b binds TLR7 to cause neurodegeneration. METHODS: TLR7 and other immune markers were assessed in postmortem human hippocampal tissue that was obtained from the New South Wales Tissue Bank...
January 25, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28117917/quantifying-the-accretion-of-hyperphosphorylated-tau-in-the-locus-coeruleus-and-dorsal-raphe-nucleus-the-pathological-building-blocks-of-early-alzheimer-s-disease
#18
Alexander J Ehrenberg, Austin K Nguy, Panos Theofilas, Sara Dunlop, Claudia K Suemoto, Ana T D L Alho, Renata Paraizo Leite, Roberta Diehl Rodriguez, Maria B Mejia, Udo Rüb, Jose M Farfel, Renata Eloah de Lucena Ferretti-Rebustini, Camila F Nascimento, Ricardo Nitrini, Carlos Augusto Pasquallucci, Wilson Jacob-Filho, Bruce Miller, William W Seeley, Helmut Heinsen, Lea T Grinberg
AIMS: Hyperphosphorylated tau-neuronal cytoplasmic inclusions (ht-NCI) are the best protein correlate of clinical decline in Alzheimer's disease (AD). Qualitative evidence identifies ht-NCI accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht-NCI burden in the locus coeruleus and dorsal raphe nucleus, aiming to characterize the impact of AD pathology in these nuclei with a focus on early stages. METHODS: We utilized unbiased stereology in a sample of 48 well-characterized subjects enriched for controls and early AD stages...
January 24, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28115477/a-deletion-variant-of-the-%C3%AE-2b-adrenoceptor-modulates-the-stress-induced-shift-from-cognitive-to-habit-memory
#19
Lisa Wirz, Jan Wacker, Andrea Felten, Martin Reuter, Lars Schwabe
: Stress induces a shift from hippocampus-based 'cognitive' towards dorsal striatum-based 'habitual' learning and memory. This shift is thought to have important implications for stress-related psychopathologies, including posttraumatic stress disorder (PTSD). However, there is large individual variability in the stress-induced bias towards habit memory and the factors underlying this variability are completely unknown. Here we hypothesized that a functional deletion variant of the gene encoding the α2b-adrenoceptor (ADRA2B), which has been linked to emotional memory processes and increased PTSD risk, modulates the stress-induced shift from cognitive towards habit memory...
January 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28111080/tau-pathology-induces-excitatory-neuron-loss-grid-cell-dysfunction-and-spatial-memory-deficits-reminiscent-of-early-alzheimer-s-disease
#20
Hongjun Fu, Gustavo A Rodriguez, Mathieu Herman, Sheina Emrani, Eden Nahmani, Geoffrey Barrett, Helen Y Figueroa, Eliana Goldberg, S Abid Hussaini, Karen E Duff
The earliest stages of Alzheimer's disease (AD) are characterized by the formation of mature tangles in the entorhinal cortex and disorientation and confusion when navigating familiar places. The medial entorhinal cortex (MEC) contains specialized neurons called grid cells that form part of the spatial navigation system. Here we show in a transgenic mouse model expressing mutant human tau predominantly in the EC that the formation of mature tangles in old mice was associated with excitatory cell loss and deficits in grid cell function, including destabilized grid fields and reduced firing rates, as well as altered network activity...
February 8, 2017: Neuron
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