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Dendritic vulnerability in neurodegenerative disease: insights from analyses of cortical pyramidal neurons in transgenic mouse models

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Abstract

In neurodegenerative disorders, such as Alzheimer’s disease, neuronal dendrites and dendritic spines undergo significant pathological changes. Because of the determinant role of these highly dynamic structures in signaling by individual neurons and ultimately in the functionality of neuronal networks that mediate cognitive functions, a detailed understanding of these changes is of paramount importance. Mutant murine models, such as the Tg2576 APP mutant mouse and the rTg4510 tau mutant mouse have been developed to provide insight into pathogenesis involving the abnormal production and aggregation of amyloid and tau proteins, because of the key role that these proteins play in neurodegenerative disease. This review showcases the multidimensional approach taken by our collaborative group to increase understanding of pathological mechanisms in neurodegenerative disease using these mouse models. This approach includes analyses of empirical 3D morphological and electrophysiological data acquired from frontal cortical pyramidal neurons using confocal laser scanning microscopy and whole-cell patch-clamp recording techniques, combined with computational modeling methodologies. These collaborative studies are designed to shed insight on the repercussions of dystrophic changes in neocortical neurons, define the cellular phenotype of differential neuronal vulnerability in relevant models of neurodegenerative disease, and provide a basis upon which to develop meaningful therapeutic strategies aimed at preventing, reversing, or compensating for neurodegenerative changes in dementia.

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References

  • Achard P, De Schutter E (2006) Complex parameter landscape for a complex neuron model. PLoS Comput Biol 2(7):e94

    PubMed  Google Scholar 

  • Al-Kofahi KA, Lasek S, Szarowski DH, Pace CJ, Nagy G, Turner JN, Roysam B (2002) Rapid automated three-dimensional tracing of neurons from confocal image stacks. IEEE Trans Inf Technol Biomed 6(2):171–187

    PubMed  Google Scholar 

  • Alvarez VA, Sabatini BL (2007) Anatomical and physiological plasticity of dendritic spines. Annu Rev Neurosci 30:79–97

    CAS  PubMed  Google Scholar 

  • Anderton BH, Callahan L, Coleman P, Davies P, Flood D, Jicha GA, Ohm T, Weaver C (1998) Dendritic changes in Alzheimer’s disease and factors that may underlie these changes. Prog Neurobiol 55(6):595–609

    CAS  PubMed  Google Scholar 

  • Andorfer C, Acker CM, Kress Y, Hof PR, Duff K, Davies P (2005) Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms. J Neurosci 25(22):5446–5454

    CAS  PubMed  Google Scholar 

  • Araya R, Jiang J, Eisenthal KB, Yuste R (2006) The spine neck filters membrane potentials. Proc Natl Acad Sci USA 103(47):17961–17966

    CAS  PubMed  Google Scholar 

  • Ascoli GA (2003) Passive dendritic integration heavily affects spiking dynamics of recurrent networks. Neural Netw 16(5–6):657–663

    PubMed  Google Scholar 

  • Baer SM, Rinzel J (1991) Propagation of dendritic spikes mediated by excitable spines: a continuum theory. J Neurophysiol 65(4):874–890

    CAS  PubMed  Google Scholar 

  • Banks DS, Fradin C (2005) Anomalous diffusion of proteins due to molecular crowding. Biophys J 89(5):2960–2971

    CAS  PubMed  Google Scholar 

  • Bekkers JM, Hausser M (2007) Targeted dendrotomy reveals active and passive contributions of the dendritic tree to synaptic integration and neuronal output. Proc Natl Acad Sci USA 104(27):11447–11452

    CAS  PubMed  Google Scholar 

  • Berger T, Larkum ME, Luscher HR (2001) High I(h) channel density in the distal apical dendrite of layer V pyramidal cells increases bidirectional attenuation of EPSPs. J Neurophysiol 85(2):855–868

    CAS  PubMed  Google Scholar 

  • Bernander O, Douglas RJ, Martin KA, Koch C (1991) Synaptic background activity influences spatiotemporal integration in single pyramidal cells. Proc Natl Acad Sci USA 88(24):11569–11573

    CAS  PubMed  Google Scholar 

  • Bhatt DH, Zhang S, Gan WB (2009) Dendritic spine dynamics. Annu Rev Physiol 71:261–282

    CAS  PubMed  Google Scholar 

  • Biscaro B, Lindvall O, Hock C, Ekdahl CT, Nitsch RM (2009) Abeta immunotherapy protects morphology and survival of adult-born neurons in doubly transgenic APP/PS1 mice. J Neurosci 29(45):14108–14119

    CAS  PubMed  Google Scholar 

  • Bloodgood BL, Sabatini BL (2005) Neuronal activity regulates diffusion across the neck of dendritic spines. Science 310(5749):866–869

    CAS  PubMed  Google Scholar 

  • Bloodgood BL, Sabatini BL (2007) Ca2+ signaling in dendritic spines. Curr Opin Neurobiol 17(3):345–351

    CAS  PubMed  Google Scholar 

  • Bourne J, Harris KM (2007) Do thin spines learn to be mushroom spines that remember? Curr Opin Neurobiol 17(3):381–386

    CAS  PubMed  Google Scholar 

  • Bower JM, Beeman D (1998) The book of genesis: exploring realistic neural models with the general neural simulation system. Springer, New York

    Google Scholar 

  • Brown TH, Zador A, Mainen ZF, Claiborne BJ (1992) Hebbian computations in hippocampal dendrites and spines. In: McKenna T, Davis J, Zornetzer SF (eds) Single neuron computation. Academic Press, San Diego, pp 81–116

  • Brown JT, Richardson JC, Collingridge GL, Randall AD, Davies CH (2005) Synaptic transmission and synchronous activity is disrupted in hippocampal slices taken from aged TAS10 mice. Hippocampus 15(1):110–117

    PubMed  Google Scholar 

  • Bucher D, Prinz AA, Marder E (2005) Animal-to-animal variability in motor pattern prediction in adults and during growth. J Neurosci 25:1611–1619

    CAS  PubMed  Google Scholar 

  • Buhl EH, Lübke J (1989) Intracellular lucifer yellow injection in fixed brain slices combined with retrograde tracing, light and electron microscopy. Neuroscience 28(1):3–16

    CAS  PubMed  Google Scholar 

  • Bussière T, Giannakopoulos P, Bouras C, Perl DP, Morrison JH, Hof PR (2003) Progressive degeneration of nonphosphorylated neurofilament protein-enriched pyramidal neurons predicts cognitive impairment in Alzheimer’s disease: stereologic analysis of prefrontal cortex area 9. J Comp Neurol 463(3):281–302

    PubMed  Google Scholar 

  • Capowski JJ (1985) The microcomputer in cell and neurobiology research. Elsevier, Amsterdam

    Google Scholar 

  • Carnevale NT, Hines ML (2006) The neuron book. Cambridge University Press, Cambridge

    Google Scholar 

  • Carnevale NT, Tsai KY, Claiborne BJ, Brown TH (1997) Comparative electrotonic analysis of three classes of rat hippocampal neurons. J Neurophysiol 78:703–720

    CAS  PubMed  Google Scholar 

  • Caserta F, Eldred WD, Fernandez E, Hausman RE, Stanford LR, Bulderev SV, Schwarzer S, Stanley HE (1995) Determination of fractal dimension of physiologically characterized neurons in two and three dimensions. J Neurosci Methods 56:133–144

    CAS  PubMed  Google Scholar 

  • Chapman PF, White GL, Jones MW, Cooper-Blacketer D, Marshall VJ, Irizarry M, Younkin L, Good MA, Bliss TV, Hyman BT, Younkin SG, Hsiao KK (1999) Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nat Neurosci 2(3):271–276

    CAS  PubMed  Google Scholar 

  • Cheng J, Zhou X, Miller E, Witt RM, Zhu J, Sabatini BL, Wong ST (2007) A novel computational approach for automatic dendrite spines detection in two-photon laser scan microscopy. J Neurosci Methods 165(1):122–134

    PubMed  Google Scholar 

  • Chiba A, Kamper G, Murphey RK (1992) Response properties of interneurons of the cricket cercal sensory system are conserved in spite of changes in peripheral receptors during maturation. J Exp Biol 164:205–226

    Google Scholar 

  • Clements JD, Redman SJ (1989) Cable properties of cat spinal motoneurones measured by combining voltage clamp, current clamp and intracellular staining. J Physiol 409:63–87

    CAS  PubMed  Google Scholar 

  • Conde C, Caceres A (2009) Microtubule assembly, organization and dynamics in axons and dendrites. Nat Rev Neurosci 10(5):319–332

    CAS  PubMed  Google Scholar 

  • Duan H, Wearne SL, Rocher AB, Macedo A, Morrison JH, Hof PR (2003) Age-related dendritic and spine changes in corticocortically projecting neurons in macaque monkeys. Cereb Cortex 13(9):950–961

    PubMed  Google Scholar 

  • Duff K, Suleman F (2004) Transgenic mouse models of Alzheimer’s disease: how useful have they been for therapeutic development? Brief Funct Genomic Proteomic 3(1):47–59

    CAS  PubMed  Google Scholar 

  • Duyckaerts C, Potier MC, Delatour B (2008) Alzheimer disease models and human neuropathology: similarities and differences. Acta Neuropathol 115(1):5–38

    PubMed  Google Scholar 

  • Euler T, Denk W (2001) Dendritic processing. Curr Opin Neurobiol 11(4):415–422

    CAS  PubMed  Google Scholar 

  • Falke E, Nissanov J, Mitchell TW, Bennett DA, Trojanowski JQ, Arnold SE (2003) Subicular dendritic arborization in Alzheimer’s disease correlates with neurofibrillary tangle density. Am J Pathol 163(4):1615–1621

    PubMed  Google Scholar 

  • Fedotov S, Méndez V (2008) Non-Markovian model for transport and reactions of particles in spiny dendrites. Phys Rev Lett 101(21):218102

    PubMed  Google Scholar 

  • Feldmeyer D, Lubke J, Silver RA, Sakmann B (2002) Synaptic connections between layer 4 spiny neurone-layer 2/3 pyramidal cell pairs in juvenile rat barrel cortex: physiology and anatomy of interlaminar signalling within a cortical column. J Physiol 538(Pt 3):803–822

    CAS  PubMed  Google Scholar 

  • Ferrer I, Guionnet N, Cruz-Sanchez F, Tunon T (1990) Neuronal alterations in patients with dementia: a Golgi study on biopsy samples. Neurosci Lett 114(1):11–16

    CAS  PubMed  Google Scholar 

  • Fitzhugh R (1961) Impulses and physiological states in theoretical models of nerve membrane. Biophys J 1:445–466

    CAS  PubMed  Google Scholar 

  • Fitzjohn SM, Morton RA, Kuenzi F, Rosahl TW, Shearman M, Lewis H, Smith D, Reynolds DS, Davies CH, Collingridge GL, Seabrook GR (2001) Age-related impairment of synaptic transmission but normal long-term potentiation in transgenic mice that overexpress the human APP695SWE mutant form of amyloid precursor protein. J Neurosci 21(13):4691–4698

    CAS  PubMed  Google Scholar 

  • Flood DG (1991) Region-specific stability of dendritic extent in normal human aging and regression in Alzheimer’s disease. II. Subiculum. Brain Res 540(1-2):83–95

    CAS  PubMed  Google Scholar 

  • Garcia-Lopez P, Garcia-Marin V, Freire M (2007) The discovery of dendritic spines by Cajal in 1888 and its relevance in the present neuroscience. Prog Neurobiol 83(2):110–130

    CAS  PubMed  Google Scholar 

  • Garcia-Marin V, Garcia-Lopez P, Freire M (2007) Cajal’s contributions to the study of Alzheimer’s disease. J Alzheimers Dis 12(2):161–174

    PubMed  Google Scholar 

  • Gertz HJ, Kruger H, Patt S, Cervos-Navarro J (1991) Tangle-bearing neurons show more extensive dendritic trees than tangle-free neurons in area CA1 of the hippocampus in Alzheimer’s disease. Brain Res 548(1–2):260–266

    CAS  PubMed  Google Scholar 

  • Giacchino J, Criado JR, Games D, Henriksen S (2000) In vivo synaptic transmission in young and aged amyloid precursor protein transgenic mice. Brain Res 876(1–2):185–190

    CAS  PubMed  Google Scholar 

  • Giannakopoulos P, Kövari E, Gold G, von Gunten A, Hof PR, Bouras C (2009) Pathological substrates of cognitive decline in Alzheimer’s disease. Front Neurol Neurosci 24:20–29

    PubMed  Google Scholar 

  • Goldman MS, Golowasch J, Marder E, Abbott LF (2001) Global structure, robustness, and modulation of neuronal models. J Neurosci 21(14):5229–5238

    CAS  PubMed  Google Scholar 

  • Goldstein SS, Rall W (1974) Changes of action potential shape and velocity for changing core conductor geometry. Biophys J 14(10):731–757

    CAS  PubMed  Google Scholar 

  • Grutzendler J, Kasthuri N, Gan WB (2002) Long-term dendritic spine stability in the adult cortex. Nature 420(6917):812–816

    CAS  PubMed  Google Scholar 

  • Hall GF, Chu B, Lee G, Yao J (2000) Human tau filaments induce microtubule and synapse loss in an in vivo model of neurofibrillary degenerative disease. J Cell Sci 113(Pt 8):1373–1387

    CAS  PubMed  Google Scholar 

  • Hall GF, Lee VM, Lee G, Yao J (2001) Staging of neurofibrillary degeneration caused by human tau overexpression in a unique cellular model of human tauopathy. Am J Pathol 158(1):235–246

    CAS  PubMed  Google Scholar 

  • Halpain S, Spencer K, Graber S (2005) Dynamics and pathology of dendritic spines. Prog Brain Res 147:29–37

    CAS  PubMed  Google Scholar 

  • Hartley DM, Walsh DM, Ye CP, Diehl T, Vasquez S, Vassilev PM, Teplow DB, Selkoe DJ (1999) Protofibrillar intermediates of amyloid beta-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons. J Neurosci 19(20):8876–8884

    CAS  PubMed  Google Scholar 

  • Hausser M, Spruston N, Stuart GJ (2000) Diversity and dynamics of dendritic signaling. Science 290(5492):739–744

    CAS  PubMed  Google Scholar 

  • He W, Hamilton TA, Cohen AR, Holmes TJ, Pace C, Szarowski DH, Turner JN, Roysam B (2003) Automated three-dimensional tracing of neurons in confocal and bright field images. Microsc Microanal 9(4):296–310

    CAS  PubMed  Google Scholar 

  • Henry BI, Hof PR, Rothnie P, Wearne SL (2002) Fractal analysis of aggregates of non-uniformly sized particles: an application to macaque monkey cortical pyramidal neurons. In: Novak MM (ed) Emergent nature: patterns, growth and scaling in the sciences. World Scientific Publishing, Singapore, pp 65–75

  • Henry BI, Langlands TA, Wearne SL (2008) Fractional cable models for spiny neuronal dendrites. Phys Rev Lett 100(12):128103

    CAS  PubMed  Google Scholar 

  • Hering H, Sheng M (2001) Dendritic spines: structure, dynamics and regulation. Nat Rev Neurosci 2(12):880–888

    CAS  PubMed  Google Scholar 

  • Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117:500–544

    CAS  PubMed  Google Scholar 

  • Hof PR, Morrison JH (2004) The aging brain: morphomolecular senescence of cortical circuits. Trends Neurosci 27:607–613

    CAS  PubMed  Google Scholar 

  • Hof PR, Cox K, Morrison JH (1990) Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer’s disease. I. Superior frontal and inferior temporal cortex. J Comp Neurol 301:44–54

    CAS  PubMed  Google Scholar 

  • Holthoff K, Tsay D, Yuste R (2002) Calcium dynamics of spines depend on their dendritic location. Neuron 33(3):425–437

    CAS  PubMed  Google Scholar 

  • Holtmaat A, Svoboda K (2009) Experience-dependent structural synaptic plasticity in the mammalian brain. Nat Rev Neurosci 10(9):647–658

    CAS  PubMed  Google Scholar 

  • Holtmaat AJ, Trachtenberg JT, Wilbrecht L, Shepherd GM, Zhang X, Knott GW, Svoboda K (2005) Transient and persistent dendritic spines in the neocortex in vivo. Neuron 45(2):279–291

    CAS  PubMed  Google Scholar 

  • Hsia AY, Masliah E, McConlogue L, Yu GQ, Tatsuno G, Hu K, Kholodenko D, Malenka RC, Nicoll RA, Mucke L (1999) Plaque-independent disruption of neural circuits in Alzheimer’s disease mouse models. Proc Natl Acad Sci USA 96(6):3228–3233

    CAS  PubMed  Google Scholar 

  • Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, Yang F, Cole G (1996) Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 274(5284):99–102

    CAS  PubMed  Google Scholar 

  • Jaslove SW (1992) The integrative properties of spiny distal dendrites. Neuroscience 47(3):495–519

    CAS  PubMed  Google Scholar 

  • Jelinek HF, Elston GN (2001) Pyramidal neurones in macaque visual cortex: interareal phenotypic variation of dendritic branching patterns. Fractals 9:297–303

    Google Scholar 

  • Johnston D, Narayanan R (2008) Active dendrites: colorful wings of the mysterious butterflies. Trends Neurosci 31(6):309–316

    CAS  PubMed  Google Scholar 

  • Johnston D, Magee JC, Colbert CM, Cristie BR (1996) Active properties of neuronal dendrites. Annu Rev Neurosci 19:165–186

    CAS  PubMed  Google Scholar 

  • Kabaso D, Coskren PJ, Henry BI, Hof PR, Wearne SL (2009) The electrotonic structure of pyramidal neurons contributing to prefrontal cortical circuits in macaque monkeys is significantly altered in aging. Cereb Cortex 19(10):2248–2268

    PubMed  Google Scholar 

  • Kamenetz F, Tomita T, Hsieh H, Seabrook G, Borchelt D, Iwatsubo T, Sisodia S, Malinow R (2003) APP processing and synaptic function. Neuron 37(6):925–937

    CAS  PubMed  Google Scholar 

  • Kampa BM, Letzkus JJ, Stuart GJ (2007) Dendritic mechanisms controlling spike-timing-dependent synaptic plasticity. Trends Neurosci 30(9):456–463

    CAS  PubMed  Google Scholar 

  • Kasai H, Matsuzaki M, Noguchi J, Yasumatsu N, Nakahara H (2003) Structure–stability–function relationships of dendritic spines. Trends Neurosci 26(7):360–368

    CAS  PubMed  Google Scholar 

  • Klyubin I, Walsh DM, Cullen WK, Fadeeva JV, Anwyl R, Selkoe DJ, Rowan MJ (2004) Soluble Arctic amyloid beta protein inhibits hippocampal long-term potentiation in vivo. Eur J Neurosci 19(10):2839–2846

    PubMed  Google Scholar 

  • Knobloch M, Mansuy IM (2008) Dendritic spine loss and synaptic alterations in Alzheimer’s disease. Mol Neurobiol 37(1):73–82

    CAS  PubMed  Google Scholar 

  • Knowles RB, Wyart C, Buldyrev SV, Cruz L, Urbanc B, Hasselmo ME, Stanley HE, Hyman BT (1999) Plaque-induced neurite abnormalities: implications for disruption of neural networks in Alzheimer's disease. Proc Natl Acad Sci USA 96(9):5274–5279

    CAS  PubMed  Google Scholar 

  • Koch C, Segev I (2000) The role of single neurons in information processing. Nat Neurosci 3(Suppl):1171–1177

    CAS  PubMed  Google Scholar 

  • Koh IY, Lindquist WB, Zito K, Nimchinsky EA, Svoboda K (2002) An image analysis algorithm for dendritic spines. Neural Comput 14(6):1283–1310

    PubMed  Google Scholar 

  • Krichmar JL, Nasuto SJ, Scorcioni R, Washington SD, Ascoli GA (2002) Effects of dendritic morphology on CA3 pyramidal cell electrophysiology: a simulation study. Brain Res 941(1–2):11–28

    CAS  PubMed  Google Scholar 

  • Kuchibhotla KV, Goldman ST, Lattarulo CR, Wu HY, Hyman BT, Bacskai BJ (2008) Abeta plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks. Neuron 59(2):214–225

    CAS  PubMed  Google Scholar 

  • Langlands TA, Henry BI, Wearne SL (2008) Anomalous subdiffusion with multispecies linear reaction dynamics. Phys Rev E Stat Nonlin Soft Matter Phys 77(2 Pt 1):021111

    CAS  PubMed  Google Scholar 

  • Langlands TA, Henry BI, Wearne SL (2009) Fractional cable equation models for anomalous electrodiffusion in nerve cells: infinite domain solutions. J Math Biol 59(6):761–808

    CAS  PubMed  Google Scholar 

  • Larson J, Lynch G, Games D, Seubert P (1999) Alterations in synaptic transmission and long-term potentiation in hippocampal slices from young and aged PDAPP mice. Brain Res 840(1–2):23–35

    CAS  PubMed  Google Scholar 

  • Le R, Cruz L, Urbanc B, Knowles RB, Hsiao-Ashe K, Duff K, Irizarry MC, Stanley HE, Hyman BT (2001) Plaque-induced abnormalities in neurite geometry in transgenic models of Alzheimer disease: implications for neural system disruption. J Neuropathol Exp Neurol 60(8):753–758

    CAS  PubMed  Google Scholar 

  • Lendvai B, Stern EA, Chen B, Svoboda K (2000) Experience-dependent plasticity of dendritic spines in the developing rat barrel cortex in vivo. Nature 404(6780):876–881

    CAS  PubMed  Google Scholar 

  • Lewis J, Hutton M (2005) Animal models of tauopathies atypical parkinsonian disorders. I. Litvan. Humana Press, Totowa, pp 65–76

    Google Scholar 

  • Liu X, Erikson C, Brun A (1996) Cortical synaptic changes and gliosis in normal aging, Alzheimer’s disease and frontal lobe degeneration. Dementia 7(3):128–134

    CAS  PubMed  Google Scholar 

  • Lombardo JA, Stern EA, McLellan ME, Kajdasz ST, Hickey GA, Bacskai BJ, Hyman BT (2003) Amyloid-beta antibody treatment leads to rapid normalization of plaque-induced neuritic alterations. J Neurosci 23:10879–10883

    CAS  PubMed  Google Scholar 

  • Lorincz A, Notomi T, Tamas G, Shigemoto R, Nusser Z (2002) Polarized and compartment-dependent distribution of HCN1 in pyramidal cell dendrites. Nat Neurosci 5(11):1185–1193

    PubMed  Google Scholar 

  • Lubke J, Egger V, Sakmann B, Feldmeyer D (2000) Columnar organization of dendrites and axons of single and synaptically coupled excitatory spiny neurons in layer 4 of the rat barrel cortex. J Neurosci 20(14):5300–5311

    CAS  PubMed  Google Scholar 

  • Magee JC, Johnston D (2005) Plasticity of dendritic function. Curr Opin Neurobiol 15(3):334–342

    CAS  PubMed  Google Scholar 

  • Mainen ZF, Sejnowski TJ (1996) Influence of dendritic structure on firing pattern in model neocortical neurons. Nature 382(6589):363–366

    CAS  PubMed  Google Scholar 

  • Matus A (2005) Growth of dendritic spines: a continuing story. Curr Opin Neurobiol 15(1):67–72

    CAS  PubMed  Google Scholar 

  • Matus A, Shepherd GM (2000) The millennium of the dendrite? Neuron 27(3):431–434

    CAS  PubMed  Google Scholar 

  • Metzler R, Klafter J (2000) Subdiffusive transport close to thermal equilibrium: from the Langevin equation to fractional diffusion. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics 61(6 Pt A):6308–6311

    CAS  PubMed  Google Scholar 

  • Migliore M, Shepherd GM (2002) Emerging rules for the distributions of active dendritic conductances. Nat Rev Neurosci 3(5):362–370

    CAS  PubMed  Google Scholar 

  • Mocanu MM, Nissen A, Eckermann K, Khlistunova I, Biernat J, Drexler D, Petrova O, Schonig K, Bujard H, Mandelkow E, Zhou L, Rune G, Mandelkow EM (2008) The potential for beta-structure in the repeat domain of tau protein determines aggregation, synaptic decay, neuronal loss, and coassembly with endogenous Tau in inducible mouse models of tauopathy. J Neurosci 28(3):737–748

    CAS  PubMed  Google Scholar 

  • Moolman DL, Vitolo OV, Vonsattel JP, Shelanski ML (2004) Dendrite and dendritic spine alterations in Alzheimer models. J Neurocytol 33(3):377–387

    CAS  PubMed  Google Scholar 

  • Morrison JH, Hof PR (1997) Life and death of neurons in the aging brain. Science 278(5337):412–419

    CAS  PubMed  Google Scholar 

  • Morrison JH, Hof PR (2002) Selective vulnerability of corticocortical and hippocampal circuits in aging and Alzheimer’s disease. Prog Brain Res 136:467–486

    CAS  PubMed  Google Scholar 

  • Mueggler T, Meyer-Luehmann M, Rausch M, Staufenbiel M, Jucker M, Rudin M (2004) Restricted diffusion in the brain of transgenic mice with cerebral amyloidosis. Eur J Neurosci 20(3):811–817

    PubMed  Google Scholar 

  • Myatt DR, Nasuto SJ, Maybank SJ (2006) Towards the automatic reconstruction of dendritic trees using particle filters. Nonlinear Statistical Signal Processing Workshop, IEEE, pp 193–196, 13–15 Sept 2006

  • Nagumo JS, Arimato S, Yoshizawa S (1962) An active pulse transmission line simulating a nerve axon. Proc IRE 50:2061–2070

    Google Scholar 

  • Neher E, Sakmann B (1976) Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature 260(5554):799–802

    CAS  PubMed  Google Scholar 

  • Nimchinsky EA, Sabatini BL, Svoboda K (2002) Structure and function of dendritic spines. Annu Rev Physiol 64:313–353

    CAS  PubMed  Google Scholar 

  • Nusser Z (2009) Variability in the subcellular distribution of ion channels increases neuronal diversity. Trends Neurosci 32(5):267–274

    CAS  PubMed  Google Scholar 

  • Nusser Z, Lujan R, Laube G, Roberts JD, Molnar E, Somogyi P (1998) Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron 21(3):545–559

    CAS  PubMed  Google Scholar 

  • Olypher AV, Calabrese RL (2007) Using constraints on neuronal activity to reveal compensatory changes in neuronal parameters. J Neurophysiol 98(6):3749–3758

    PubMed  Google Scholar 

  • Paula-Barbosa MM, Cardoso RM, Guimaraes ML, Cruz C (1980) Dendritic degeneration and regrowth in the cerebral cortex of patients with Alzheimer’s disease. J Neurol Sci 45(1):129–134

    CAS  PubMed  Google Scholar 

  • Pinsky PF, Rinzel J (1994) Intrinsic and network rhythmogenesis in a reduced Traub model for CA3 neurons. J Comp Neurosci 1:39–60

    CAS  Google Scholar 

  • Prinz AA, Billimoria CP, Marder E (2003) Alternative to hand-tuning conductance-based models: construction and analysis of databases of model neurons. J Neurophysiol 90(6):3998–4015

    PubMed  Google Scholar 

  • Prinz AA, Bucher D, Marder E (2004) Similar network activity from disparate circuit parameters. Nat Neurosci 7(12):1345–1352

    CAS  PubMed  Google Scholar 

  • Probst A, Basler V, Bron B, Ulrich J (1983) Neuritic plaques in senile dementia of Alzheimer type: a Golgi analysis in the hippocampal region. Brain Res 268(2):249–254

    CAS  PubMed  Google Scholar 

  • Rall W (1959) Branching dendritic trees and motoneuron membrane resistivity. Exp Neurol 1:491–527

    CAS  PubMed  Google Scholar 

  • Rall W (1969) Time constants and electrotonic length of membrane cylinders and neurons. Biophys J 9:1483–1508

    CAS  PubMed  Google Scholar 

  • Ramón y Cajal S (1911) Histologie du systeme nerveux de l’homme et des vertébrés. Masson, Paris

    Google Scholar 

  • Rho JH, Sidman RL (1986) Intracellular injection of lucifer yellow into lightly fixed cerebellar neurons. Neurosci Lett 72(1):21–24

    CAS  PubMed  Google Scholar 

  • Ridler TW, Calvard S (1978) Picture thresholding using an iterative selection method. IEEE Trans Syst Man Cybern SMC-8:630–632

    Google Scholar 

  • Rinzel J, Ermentrout GB (1989) Analysis of neuronal excitability and oscillations. In: Koch C, Segev I (eds) Methods in neuronal modeling: from ions to networks. The MIT Press, Cambridge, pp 251–291

    Google Scholar 

  • Rocher AB, Kinson MS, Luebke JI (2008) Significant structural but not physiological changes in cortical neurons of 12-month-old Tg2576 mice. Neurobiol Dis 32(2):309–318

    CAS  PubMed  Google Scholar 

  • Rocher AB, Crimins JL, Amatrudo JM, Kinson MS, Todd-Brown MA, Lewis J, Luebke JI (2009) Structural and functional changes in tau mutant mice neurons are not linked to the presence of NFTs. Exp Neurol [Epub ahead of print]

  • Rockland KS, Pandya DN (1979) Laminar origins and terminations of cortical connections of the occipital lobe in the rhesus monkey. Brain Res 179(1):3–20

    CAS  PubMed  Google Scholar 

  • Roder S, Danober L, Pozza MF, Lingenhoehl K, Wiederhold KH, Olpe HR (2003) Electrophysiological studies on the hippocampus and prefrontal cortex assessing the effects of amyloidosis in amyloid precursor protein 23 transgenic mice. Neuroscience 120(3):705–720

    CAS  PubMed  Google Scholar 

  • Rodriguez A, Ehlenberger D, Kelliher K, Einstein M, Henderson SC, Morrison JH, Hof PR, Wearne SL (2003) Automated reconstruction of three-dimensional neuronal morphology from laser scanning microscopy images. Methods 30(1):94–105

    CAS  PubMed  Google Scholar 

  • Rodriguez A, Ehlenberger DB, Hof PR, Wearne SL (2006) Rayburst sampling, an algorithm for automated three-dimensional shape analysis from laser scanning microscopy images. Nat Protoc 1(4):2152–2161

    CAS  PubMed  Google Scholar 

  • Rodriguez A, Ehlenberger DB, Dickstein DL, Hof PR, Wearne SL (2008) Automated three-dimensional detection and shape classification of dendritic spines from fluorescence microscopy images. PLoS One 3(4):e1997

    PubMed  Google Scholar 

  • Rodriguez A, Ehlenberger DB, Hof PR, Wearne SL (2009) Three-dimensional neuron tracing by voxel scooping. J Neurosci Methods 184(1):169–175

    PubMed  Google Scholar 

  • Rothnie P, Kabaso D, Hof PR, Henry BI, Wearne SL (2006) Functionally relevant measures of spatial complexity in neuronal dendritic arbors. J Theor Biol 238(3):505–526

    CAS  PubMed  Google Scholar 

  • Rozkalne A, Spires-Jones TL, Stern EA, Hyman BT (2009) A single dose of passive immunotherapy has extended benefits on synapses, neuritis in an Alzheimer’s disease mouse model. Brain Res 1280:178–185

    CAS  PubMed  Google Scholar 

  • Saftenku EE (2009) Computational study of non-homogeneous distribution of Ca2+ handling systems in cerebellar granule cells. J Theor Biol 257(2):228–244

    CAS  PubMed  Google Scholar 

  • Saltelli A, Chan K, Scott EM (eds) (2000) Sensitivity analysis. Wiley, New York

    Google Scholar 

  • Samsonovich AV, Ascoli GA (2006) Morphological homeostasis in cortical dendrites. Proc Natl Acad Sci USA 103(5):1569–1574

    CAS  PubMed  Google Scholar 

  • Santacruz K, Lewis J, Spires T, Paulson J, Kotilinek L, Ingelsson M, Guimaraes A, DeTure M, Ramsden M, McGowan E, Forster C, Yue M, Orne J, Janus C, Mariash A, Kuskowski M, Hyman B, Hutton M, Ashe KH (2005) Tau suppression in a neurodegenerative mouse model improves memory function. Science 309(5733):476–481

    CAS  PubMed  Google Scholar 

  • Santamaria F, Wils S, De Schutter E, Augustine GJ (2006) Anomalous diffusion in Purkinje cell dendrites caused by spines. Neuron 52(4):635–648

    CAS  PubMed  Google Scholar 

  • Santamaria-Pang A, Colbert CM, Saggau P, Kakadiaris IA (2007) Automatic centerline extraction of irregular tubular structures using probability volumes from multiphoton imaging. Int Conf Med Image Comput Comput Assist Interv 10(Pt 2):486–494

    CAS  Google Scholar 

  • Schaefer AT, Larkum ME, Sakmann B, Roth A (2003) Coincidence detection in pyramidal neurons is tuned by their dendritic branching pattern. J Neurophysiol 89(6):3143–3154

    PubMed  Google Scholar 

  • Schikorski T, Stevens CF (1999) Quantitative fine-structural analysis of olfactory cortical synapses. Proc Natl Acad Sci USA 96(7):4107–4112

    CAS  PubMed  Google Scholar 

  • Schindowski K, Bretteville A, Leroy K, Begard S, Brion JP, Hamdane M, Buee L (2006) Alzheimer’s disease-like tau neuropathology leads to memory deficits and loss of functional synapses in a novel mutated tau transgenic mouse without any motor deficits. Am J Pathol 169(2):599–616

    CAS  PubMed  Google Scholar 

  • Schmidt H, Eilers J (2009) Spine neck geometry determines spino-dendritic cross-talk in the presence of mobile endogenous calcium binding proteins. J Comput Neurosci 27(2):229–243

    PubMed  Google Scholar 

  • Schmidt H, Kunerth S, Wilms C, Strotmann R, Eilers J (2007) Spinodendritic cross-talk in rodent Purkinje neurons mediated by endogenous Ca2+-binding proteins. J Physiol 581(Pt 2):619–629

    PubMed  Google Scholar 

  • Schmitt S, Evers JF, Duch C, Scholz M, Obermayer K (2004) New methods for the computer-assisted 3-D reconstruction of neurons from confocal image stacks. Neuroimage 23(4):1283–1298

    PubMed  Google Scholar 

  • Schulz DJ, Goaillard JM, Marder E (2006) Variable channel expression in identified single and electrically coupled neurons in different animals. Nat Neurosci 9:356–362

    CAS  PubMed  Google Scholar 

  • Scorcioni R, Ascoli GA (2001) Algorithmic extraction of morphological statistics from electronic archives of neuroanatomy. In: Mira J, Prieto A (eds) Lecture notes in computer science. Springer, Berlin, pp 30–37

    Google Scholar 

  • Scott SA (1993) Dendritic atrophy and remodeling of amygdaloid neurons in Alzheimer’s disease. Dementia 4(5):264–272

    CAS  PubMed  Google Scholar 

  • Segev I, London M (2000) Untangling dendrites with quantitative models. Science 290(5492):744–750

    CAS  PubMed  Google Scholar 

  • Sholl DA (1953) Dendritic organization in the neurons of the visual and motor cortices of the cat. J Anat 87:387–406

    CAS  PubMed  Google Scholar 

  • Smith TG, Marks WB, Lange GD, Sheriff JWH, Neale EA (1989) A fractal analysis of cell images. J Neurosci Methods 27:173–180

    PubMed  Google Scholar 

  • Smith DL, Pozueta J, Gong B, Arancio O, Shelanski M (2009) Reversal of long-term dendritic spine alterations in Alzheimer disease models. Proc Natl Acad Sci USA 106(39):16877–16882

    CAS  PubMed  Google Scholar 

  • Spires TL, Hyman BT (2004) Neuronal structure is altered by amyloid plaques. Rev Neurosci 15(4):267–278

    PubMed  Google Scholar 

  • Spires TL, Meyer-Luehmann M, Stern EA, McLean PJ, Skoch J, Nguyen PT, Bacskai BJ, Hyman BT (2005) Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy. J Neurosci 25(31):7278–7287

    CAS  PubMed  Google Scholar 

  • Spires-Jones TL, Stoothoff WH, de Calignon A, Jones PB, Hyman BT (2009) Tau pathophysiology in neurodegeneration: a tangled issue. Trends Neurosci 32(3):150–159

    CAS  PubMed  Google Scholar 

  • Spruston N (2008) Pyramidal neurons: dendritic structure and synaptic integration. Nat Rev Neurosci 9(3):206–221

    CAS  PubMed  Google Scholar 

  • Stern EA, Bacskai BJ, Hickey GA, Attenello FJ, Lombardo JA, Hyman BT (2004) Cortical synaptic integration in vivo is disrupted by amyloid-beta plaques. J Neurosci 24(19):4535–4540

    CAS  PubMed  Google Scholar 

  • Stiefel KM, Sejnowski TJ (2007) Mapping function onto neuronal morphology. J Neurophysiol 98(1):513–526

    PubMed  Google Scholar 

  • Stratford K, Mason A, Larkman AU, Major G, Jack JJB (1989) The modelling of pyramidal neurones in the visual cortex. In: Durbin R, Miall C, Mitchison G (eds) The computing neuron. Addison-Wesley, Wokingham, pp 296–321

    Google Scholar 

  • Streekstra GJ, van Pelt J (2002) Analysis of tubular structures in three-dimensional confocal images. Network 13(3):381–395

    PubMed  Google Scholar 

  • Stuart G, Spruston N (2007) Dendrites. Oxford University Press, Oxford

    Google Scholar 

  • Stuart G, Spruston N, Sakmann B, Hausser M (1997) Action potential initiation and backpropagation in neurons of the mammalian CNS. Trends Neurosci 20(3):125–131

    CAS  PubMed  Google Scholar 

  • Surkis A, Peskin CS, Tranchina D, Leonard CS (1998) Recovery of cable properties through active and passive modeling of subthreshold membrane responses from laterodorsal tegmental neurons. J Neurophysiol 80(5):2593–2607

    CAS  PubMed  Google Scholar 

  • Svoboda K, Tank DW, Denk W (1996) Direct measurement of coupling between dendritic spines and shafts. Science 272(5262):716–719

    CAS  PubMed  Google Scholar 

  • Swensen AM, Bean BP (2005) Robustness of burst firing in dissociated purkinje neurons with acute or long-term reductions in sodium conductance. J Neurosci 25(14):3509–3520

    CAS  PubMed  Google Scholar 

  • Tackenberg C, Ghori A, Brandt R (2009) Thin, stubby or mushroom: spine pathology in Alzheimer’s disease. Curr Alzheimer Res 6(3):261–268

    CAS  PubMed  Google Scholar 

  • Taylor AL, Goaillard JM, Marder E (2009) How multiple conductances determine electrophysiological properties in a multicompartment model. J Neurosci 29(17):5573–5586

    CAS  PubMed  Google Scholar 

  • Thierry AM, Godbout R, Mantz J, Glowinski J (1990) Influence of the ascending monoaminergic systems on the activity of the rat prefrontal cortex. Prog Brain Res 85:357–364 discussion 364-365

    CAS  PubMed  Google Scholar 

  • Trachtenberg JT, Chen BE, Knott GW, Feng G, Sanes JR, Welker E, Svoboda K (2002) Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420(6917):788–794

    CAS  PubMed  Google Scholar 

  • Tsai KY, Carnevale NT, Claiborne BJ, Brown TH (1994) Efficient mapping from neuroanatomical to electrotonic space. Networks 5:21–46

    Google Scholar 

  • Tsai J, Grutzendler J, Duff K, Gan WB (2004) Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches. Nat Neurosci 7(11):1181–1183

    CAS  PubMed  Google Scholar 

  • Tsay D, Yuste R (2002) Role of dendritic spines in action potential backpropagation: a numerical simulation study. J Neurophysiol 88(5):2834–2845

    CAS  PubMed  Google Scholar 

  • Urbanc B, Cruz L, Le R, Sanders J, Ashe KH, Duff K, Stanley HE, Irizarry MC, Hyman BT (2002) Neurotoxic effects of thioflavin S-positive amyloid deposits in transgenic mice and Alzheimer's disease. Proc Natl Acad Sci USA 99(22):13990–13995

    CAS  PubMed  Google Scholar 

  • van Groen T, Kadish I, Wyss JM (1999) Efferent connections of the anteromedial nucleus of the thalamus of the rat. Brain Res Brain Res Rev 30(1):1–26

    PubMed  Google Scholar 

  • Vetter P, Roth A, Hausser M (2001) Propagation of action potentials in dendrites depends on dendritic morphology. J Neurophysiol 85(2):926–937

    CAS  PubMed  Google Scholar 

  • Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416(6880):535–539

    CAS  PubMed  Google Scholar 

  • Wang Q, Walsh DM, Rowan MJ, Selkoe DJ, Anwyl R (2004) Block of long-term potentiation by naturally secreted and synthetic amyloid beta-peptide in hippocampal slices is mediated via activation of the kinases c-Jun N-terminal kinase, cyclin-dependent kinase 5, and p38 mitogen-activated protein kinase as well as metabotropic glutamate receptor type 5. J Neurosci 24(13):3370–3378

    CAS  PubMed  Google Scholar 

  • Waters J, Schaefer A, Sakmann B (2005) Backpropagating action potentials in neurones: measurement, mechanisms and potential functions. Prog Biophys Mol Biol 87(1):145–170

    PubMed  Google Scholar 

  • Wearne SL, Rodriguez A, Ehlenberger DB, Rocher AB, Henderson SC, Hof PR (2005) New techniques for imaging, digitization and analysis of three-dimensional neural morphology on multiple scales. Neuroscience 136(3):661–680

    CAS  PubMed  Google Scholar 

  • Weaver CM, Wearne SL (2008) Neuronal firing sensitivity to morphologic and active membrane parameters. PLoS Comput Biol 4(1):e11

    PubMed  Google Scholar 

  • Wilson CJ (1988) Cellular mechanisms controlling the strength of synapses. J Electron Microsc Tech 10(3):293–313

    CAS  PubMed  Google Scholar 

  • Yadav A, Weaver CM, Gao YZ, Luebke JI, Wearne SL (2008a) Altered mechanisms of calcium handling with age in neocortical neurons: the role of spine size and background synaptic activity 2008 Neuroscience Meeting Planner. Society for Neuroscience, Program no. 43.20, Washington, DC

  • Yadav A, Weaver CM, Gao YZ, Luebke JI, Wearne SL (2008b). Why are pyramidal cell firing rates increased with aging, and what can we do about it? Proceedings of CNS Meeting, Portland

  • Yadav A, Weaver CM, Gao YZ, Luebke JI, Wearne SL (2009) Quantifying functional flexibility of a neuron: Effects of age-related morphologic dystrophy in pyramidal neurons of the prefrontal cortex. 2009 Neuroscience Meeting Planner. Society for Neuroscience, Program no. 623.22, Chicago

  • Ye CP, Selkoe DJ, Hartley DM (2003) Protofibrils of amyloid beta-protein inhibit specific K+ currents in neocortical cultures. Neurobiol Dis 13(3):177–190

    CAS  PubMed  Google Scholar 

  • Yuste R, Bonhoeffer T (2001) Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu Rev Neurosci 24:1071–1089

    CAS  PubMed  Google Scholar 

  • Yuste R, Bonhoeffer T (2004) Genesis of dendritic spines: insights from ultrastructural and imaging studies. Nat Rev Neurosci 5(1):24–34

    CAS  PubMed  Google Scholar 

  • Yuste R, Majewska A, Holthoff K (2000) From form to function: calcium compartmentalization in dendritic spines. Nat Neurosci 3(7):653–659

    CAS  PubMed  Google Scholar 

  • Zador AM, Agmon-Snir H, Segev I (1995) The morphoelectrotonic transform: a graphical approach to dendritic function. J Neurosci 15:1669–1682

    CAS  PubMed  Google Scholar 

  • Zuo Y, Lin A, Chang P, Gan WB (2005) Development of long-term dendritic spine stability in diverse regions of cerebral cortex. Neuron 46(2):181–189

    CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Dr B.I. Henry and all the members of the Wearne, Luebke, and Hof laboratories for their participation in these studies. This work was supported by NIH Grants AG00001, AG02219, AG05138, AG025062, MH58911, MH071818, DC05669, and Australian Research Council Discovery Grant DP0665482.

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Authors and Affiliations

  1. M949, Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, 02118, USA

    Jennifer I. Luebke, Anne B. Rocher & Johanna L. Crimins

  2. Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA

    Alfredo Rodriguez, Dara L. Dickstein & Patrick R. Hof

  3. Computational Neurobiology and Imaging Center, Mount Sinai School of Medicine, New York, NY, USA

    Christina M. Weaver, Alfredo Rodriguez, Dara L. Dickstein, Susan L. Wearne & Patrick R. Hof

  4. Department of Mathematics and Computer Science, Franklin and Marshall College, Lancaster, PA, USA

    Christina M. Weaver

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  1. Jennifer I. Luebke
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  2. Christina M. Weaver
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Correspondence to Jennifer I. Luebke.

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This review is dedicated to the memory of our beloved friend, mentor, and colleague Susan L. Wearne, who passed away in September 2009.

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Luebke, J.I., Weaver, C.M., Rocher, A.B. et al. Dendritic vulnerability in neurodegenerative disease: insights from analyses of cortical pyramidal neurons in transgenic mouse models. Brain Struct Funct 214, 181–199 (2010). https://doi.org/10.1007/s00429-010-0244-2

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