FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2760721217> ?p ?o ?g. }

• W2760721217 endingPage "55" @default.
• W2760721217 startingPage "43" @default.
• W2760721217 abstract "Since Cajal’s first drawings of Golgi stained neurons, generations of researchers have been fascinated by the small protrusions, termed spines, studding many neuronal dendrites. Most excitatory synapses in the mammalian CNS are located on dendritic spines, making spines convenient proxies for excitatory synaptic presence. When in vivo imaging revealed that dendritic spines are dynamic structures, their addition and elimination were interpreted as excitatory synapse gain and loss, respectively. Spine imaging has since become a popular assay for excitatory circuit remodeling. In this review, we re-evaluate the validity of using spine dynamics as a straightforward reflection of circuit rewiring. Recent studies tracking both spines and synaptic markers in vivo reveal that 20% of spines lack PSD-95 and are short lived. Although they account for most spine dynamics, their remodeling is unlikely to impact long-term network structure. We discuss distinct roles that spine dynamics can play in circuit remodeling depending on synaptic content. Since Cajal’s first drawings of Golgi stained neurons, generations of researchers have been fascinated by the small protrusions, termed spines, studding many neuronal dendrites. Most excitatory synapses in the mammalian CNS are located on dendritic spines, making spines convenient proxies for excitatory synaptic presence. When in vivo imaging revealed that dendritic spines are dynamic structures, their addition and elimination were interpreted as excitatory synapse gain and loss, respectively. Spine imaging has since become a popular assay for excitatory circuit remodeling. In this review, we re-evaluate the validity of using spine dynamics as a straightforward reflection of circuit rewiring. Recent studies tracking both spines and synaptic markers in vivo reveal that 20% of spines lack PSD-95 and are short lived. Although they account for most spine dynamics, their remodeling is unlikely to impact long-term network structure. We discuss distinct roles that spine dynamics can play in circuit remodeling depending on synaptic content. For over a hundred years now, since Santiago Ramón y Cajal first published his seminal work using Golgi staining to reveal the fine architecture of neurons in fixed slices, the fine protrusions studding the dendrites of many neurons depicted in his detailed camera lucida drawings have fascinated generations of neuroscientists (Ramón y Cajal, 1893Ramón y Cajal S. Neue darstellung vom histologischen bau des centralnervensystem.Arch Anat Entwick. 1893; : 319-428Google Scholar). In his Neuron Doctrine, Cajal postulated that the nervous system was composed of discrete neurons rather than a contiguous network of cells as was the popular theory espoused by luminaries such as Golgi himself (DeFelipe, 2015DeFelipe J. The dendritic spine story: An intriguing process of discovery.Front. Neuroanat. 2015; 9: 14Crossref PubMed Scopus (18) Google Scholar). Cajal also postulated that the dendritic protrusions, which came to be known as spines, were points of contact between two neurons and that, in reaching out from the dendritic shaft, they could facilitate diverse connections with axons from many different sources. Later, Sherrington and others introduced the concept of the synapse as the site of chemical neurotransmission between neurons (reviewed in Shepherd and Erulkar, 1997Shepherd G.M. Erulkar S.D. Centenary of the synapse: From Sherrington to the molecular biology of the synapse and beyond.Trends Neurosci. 1997; 20: 385-392Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar), although techniques available at the time were not able to resolve the synaptic cleft between a spine and an axonal bouton. It was not until the advent of electron microscopy (EM), that researchers were able to directly visualize the synapses on dendritic spines (Gray, 1959aGray E.G. Axo-somatic and axo-dendritic synapses of the cerebral cortex: An electron microscope study.J. Anat. 1959; 93: 420-433PubMed Google Scholar, Gray, 1959bGray E.G. Electron microscopy of synaptic contacts on dendrite spines of the cerebral cortex.Nature. 1959; 183: 1592-1593Crossref PubMed Scopus (227) Google Scholar) and show that spines were the major sites of excitatory synaptic transmission (Uchizono, 1965Uchizono K. Characteristics of excitatory and inhibitory synapses in the central nervous system of the cat.Nature. 1965; 207: 642-643Crossref PubMed Scopus (0) Google Scholar). For the next several decades, methods for visualizing neuronal structure were static, providing snapshots of the neuron at the time of fixation for EM or other light microscopy. Without the ability to track the same neuron over time, inferences about spine dynamics could only be made at the population level, by comparing groups of samples fixed at different ages or after different manipulations. In the mid 1990s, use of fluorescent dyes as cell fills allowed for the first repeated monitoring of spines, revealing their dynamic nature in cultured neurons (Fischer et al., 1998Fischer M. Kaech S. Knutti D. Matus A. Rapid actin-based plasticity in dendritic spines.Neuron. 1998; 20: 847-854Abstract Full Text Full Text PDF PubMed Scopus (714) Google Scholar, Ziv and Smith, 1996Ziv N.E. Smith S.J. Evidence for a role of dendritic filopodia in synaptogenesis and spine formation.Neuron. 1996; 17: 91-102Abstract Full Text Full Text PDF PubMed Scopus (614) Google Scholar) and brain slices (Dailey and Smith, 1996Dailey M.E. Smith S.J. The dynamics of dendritic structure in developing hippocampal slices.J. Neurosci. 1996; 16: 2983-2994Crossref PubMed Google Scholar). At the same time, the introduction of fluorescent proteins for neuronal visualization opened the door for their genetic labeling and long-term tracking (Chalfie et al., 1994Chalfie M. Tu Y. Euskirchen G. Ward W.W. Prasher D.C. Green fluorescent protein as a marker for gene expression.Science. 1994; 263: 802-805Crossref PubMed Google Scholar, Chen et al., 2000aChen B.E. Lendvai B. Nimchinsky E.A. Burbach B. Fox K. Svoboda K. Imaging high-resolution structure of GFP-expressing neurons in neocortex in vivo.Learn. Mem. 2000; 7: 433-441Crossref PubMed Scopus (0) Google Scholar, Moriyoshi et al., 1996Moriyoshi K. Richards L.J. Akazawa C. O’Leary D.D. Nakanishi S. Labeling neural cells using adenoviral gene transfer of membrane-targeted GFP.Neuron. 1996; 16: 255-260Abstract Full Text Full Text PDF PubMed Scopus (219) Google Scholar). However, the limitations of conventional light microscopy would have relegated such studies to in vitro culture or slice preparations if not for the fortuitous development around the same period of the ultrafast pulsed lasers that ushered in the age of two-photon microscopy (Denk et al., 1990Denk W. Strickler J.H. Webb W.W. Two-photon laser scanning fluorescence microscopy.Science. 1990; 248: 73-76Crossref PubMed Google Scholar, Denk et al., 1994Denk W. Delaney K.R. Gelperin A. Kleinfeld D. Strowbridge B.W. Tank D.W. Yuste R. Anatomical and functional imaging of neurons using 2-photon laser scanning microscopy.J. Neurosci. Methods. 1994; 54: 151-162Crossref PubMed Scopus (241) Google Scholar). The combination of fluorescent cell fills with two-photon microscopy allowed for imaging of structures deep within scattering tissues such as the brain (reviewed in Denk and Svoboda, 1997Denk W. Svoboda K. Photon upmanship: Why multiphoton imaging is more than a gimmick.Neuron. 1997; 18: 351-357Abstract Full Text Full Text PDF PubMed Scopus (487) Google Scholar, So et al., 2000So P.T. Dong C.Y. Masters B.R. Berland K.M. Two-photon excitation fluorescence microscopy.Annu. Rev. Biomed. Eng. 2000; 2: 399-429Crossref PubMed Google Scholar). Using this technique, dendritic spines could be seen in situ in brain slices (Dunaevsky et al., 1999Dunaevsky A. Tashiro A. Majewska A. Mason C. Yuste R. Developmental regulation of spine motility in the mammalian central nervous system.Proc. Natl. Acad. Sci. USA. 1999; 96: 13438-13443Crossref PubMed Scopus (324) Google Scholar, Engert and Bonhoeffer, 1999Engert F. Bonhoeffer T. Dendritic spine changes associated with hippocampal long-term synaptic plasticity.Nature. 1999; 399: 66-70Crossref PubMed Scopus (1183) Google Scholar, Maletic-Savatic et al., 1999Maletic-Savatic M. Malinow R. Svoboda K. Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity.Science. 1999; 283: 1923-1927Crossref PubMed Scopus (900) Google Scholar) and later in vivo (Grutzendler et al., 2002Grutzendler J. Kasthuri N. Gan W.-B. Long-term dendritic spine stability in the adult cortex.Nature. 2002; 420: 812-816Crossref PubMed Scopus (761) Google Scholar, Holtmaat et al., 2005Holtmaat A.J. Trachtenberg J.T. Wilbrecht L. Shepherd G.M. Zhang X. Knott G.W. Svoboda K. Transient and persistent dendritic spines in the neocortex in vivo.Neuron. 2005; 45: 279-291Abstract Full Text Full Text PDF PubMed Scopus (645) Google Scholar, Lendvai et al., 2000Lendvai B. Stern E.A. Chen B. Svoboda K. Experience-dependent plasticity of dendritic spines in the developing rat barrel cortex in vivo.Nature. 2000; 404: 876-881Crossref PubMed Scopus (535) Google Scholar, Trachtenberg et al., 2002Trachtenberg J.T. Chen B.E. Knott G.W. Feng G. Sanes J.R. Welker E. Svoboda K. Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex.Nature. 2002; 420: 788-794Crossref PubMed Scopus (1246) Google Scholar) changing their shape and size, as well as forming or disappearing across an animal’s lifespan. Spine dynamics were shown to be responsive to both the animal’s experience and environment (reviewed in Holtmaat and Svoboda, 2009Holtmaat A. Svoboda K. Experience-dependent structural synaptic plasticity in the mammalian brain.Nat. Rev. Neurosci. 2009; 10: 647-658Crossref PubMed Scopus (917) Google Scholar), and changes in their size and shape have become accepted markers for changes in synaptic strength or synaptic presence (reviewed in Bhatt et al., 2009Bhatt D.H. Zhang S. Gan W.B. Dendritic spine dynamics.Annu. Rev. Physiol. 2009; 71: 261-282Crossref PubMed Scopus (218) Google Scholar). The view of spines as readily identifiable morphological surrogates for excitatory synapses is largely based on EM studies of the mature brain, showing that very few excitatory synapses onto excitatory neurons are located on the dendritic shaft, and the vast majority of spines contain a single excitatory synapse (Harris et al., 1992Harris K.M. Jensen F.E. Tsao B. Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: Implications for the maturation of synaptic physiology and long-term potentiation.J. Neurosci. 1992; 12: 2685-2705Crossref PubMed Google Scholar, LeVay, 1973LeVay S. Synaptic patterns in the visual cortex of the cat and monkey. Electron microscopy of Golgi preparations.J. Comp. Neurol. 1973; 150: 53-85Crossref PubMed Google Scholar). Despite this almost one-to-one correspondence between spines and excitatory synaptic presence assessed by EM, when visualizing an individual spine in vivo it is impossible to deduce whether it in fact contains a synapse by morphological criteria alone. This is particularly true when the spine is newly formed (Knott et al., 2006Knott G.W. Holtmaat A. Wilbrecht L. Welker E. Svoboda K. Spine growth precedes synapse formation in the adult neocortex in vivo.Nat. Neurosci. 2006; 9: 1117-1124Crossref PubMed Scopus (352) Google Scholar). Recently, methods for direct synaptic labeling are allowing a re-evaluation of the relationship between spine and synapse dynamics. Here, we review our evolving understanding of spine dynamics and caution that not all spine changes necessarily reflect long-lived alterations in circuit connectivity. While most spines in the adult contain a post synaptic density visible by EM (Arellano et al., 2007bArellano J.I. Espinosa A. Fairén A. Yuste R. DeFelipe J. Non-synaptic dendritic spines in neocortex.Neuroscience. 2007; 145: 464-469Crossref PubMed Scopus (0) Google Scholar), a significant fraction lack the key excitatory synaptic scaffold protein PSD-95 required for synaptic stabilization (Cane et al., 2014Cane M. Maco B. Knott G. Holtmaat A. The relationship between PSD-95 clustering and spine stability in vivo.J. Neurosci. 2014; 34: 2075-2086Crossref PubMed Scopus (60) Google Scholar, Villa et al., 2016Villa K.L. Berry K.P. Subramanian J. Cha J.W. Oh W.C. Kwon H.B. So P.T.C. Kubota Y. Nedivi E. Inhibitory synapses are repeatedly assembled and removed at persistent sites in vivo.Neuron. 2016; 89: 756-769Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar). These spines lacking PSD-95 account for the majority of spine dynamics and likely represent an effort to test new partners by forming transient connections, few of whom eventually survive (Cane et al., 2014Cane M. Maco B. Knott G. Holtmaat A. The relationship between PSD-95 clustering and spine stability in vivo.J. Neurosci. 2014; 34: 2075-2086Crossref PubMed Scopus (60) Google Scholar, Holtmaat et al., 2005Holtmaat A.J. Trachtenberg J.T. Wilbrecht L. Shepherd G.M. Zhang X. Knott G.W. Svoboda K. Transient and persistent dendritic spines in the neocortex in vivo.Neuron. 2005; 45: 279-291Abstract Full Text Full Text PDF PubMed Scopus (645) Google Scholar, Villa et al., 2016Villa K.L. Berry K.P. Subramanian J. Cha J.W. Oh W.C. Kwon H.B. So P.T.C. Kubota Y. Nedivi E. Inhibitory synapses are repeatedly assembled and removed at persistent sites in vivo.Neuron. 2016; 89: 756-769Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, Zuo et al., 2005aZuo Y. Lin A. Chang P. Gan W.B. Development of long-term dendritic spine stability in diverse regions of cerebral cortex.Neuron. 2005; 46: 181-189Abstract Full Text Full Text PDF PubMed Scopus (376) Google Scholar). We discuss imaging strategies that can discriminate between transient and long-lasting spine remodeling and best practices for their faithful interpretation. In EM micrographs, spines characteristically contain what is classified as a type 1 asymmetric synapse, defined as a synapse containing a protein rich postsynaptic density (PSD) apposed by a presynaptic axon containing round presynaptic vesicles (Gray, 1959aGray E.G. Axo-somatic and axo-dendritic synapses of the cerebral cortex: An electron microscope study.J. Anat. 1959; 93: 420-433PubMed Google Scholar, Gray, 1959bGray E.G. Electron microscopy of synaptic contacts on dendrite spines of the cerebral cortex.Nature. 1959; 183: 1592-1593Crossref PubMed Scopus (227) Google Scholar, Hersch and White, 1981Hersch S.M. White E.L. Quantification of synapses formed with apical dendrites of Golgi-impregnated pyramidal cells: Variability in thalamocortical inputs, but consistency in the ratios of asymmetrical to symmetrical synapses.Neuroscience. 1981; 6: 1043-1051Crossref PubMed Scopus (40) Google Scholar, LeVay, 1973LeVay S. Synaptic patterns in the visual cortex of the cat and monkey. Electron microscopy of Golgi preparations.J. Comp. Neurol. 1973; 150: 53-85Crossref PubMed Google Scholar, Parnavelas et al., 1977Parnavelas J.G. Sullivan K. Lieberman A.R. Webster K.E. Neurons and their synaptic organization in the visual cortex of the rat. Electron microscopy of Golgi preparations.Cell Tissue Res. 1977; 183: 499-517Crossref PubMed Google Scholar). Type 1 synapses were linked with excitatory inputs after electrophysiology experiments in the cerebellum showed the excitatory nature of granule cell input onto Purkinje cell dendrites (Uchizono, 1965Uchizono K. Characteristics of excitatory and inhibitory synapses in the central nervous system of the cat.Nature. 1965; 207: 642-643Crossref PubMed Scopus (0) Google Scholar). Later, immuno-EM showed that axons positive for the excitatory neurotransmitter glutamate only form connections with type 1 synapses and not type 2 symmetric synapses, which lack a visible PSD and are typically inhibitory (DeFelipe et al., 1988DeFelipe J. Conti F. Van Eyck S.L. Manzoni T. Demonstration of glutamate-positive axon terminals forming asymmetric synapses in cat neocortex.Brain Res. 1988; 455: 162-165Crossref PubMed Scopus (60) Google Scholar). The PSD that defines type 1 synapses has been identified as a complex network of proteins forming a highly regulated scaffold that anchors the glutamate receptors at excitatory synapses (reviewed in Sheng and Hoogenraad, 2007Sheng M. Hoogenraad C.C. The postsynaptic architecture of excitatory synapses: A more quantitative view.Annu. Rev. Biochem. 2007; 76: 823-847Crossref PubMed Scopus (510) Google Scholar). During early neuronal development, the majority of type 1 synapses on pyramidal neurons are located on the shaft, but, as spines begin to form, excitatory synapses on spines gradually replace the dendritic shaft population (reviewed in Yuste and Bonhoeffer, 2004Yuste R. Bonhoeffer T. Genesis of dendritic spines: Insights from ultrastructural and imaging studies.Nat. Rev. Neurosci. 2004; 5: 24-34Crossref PubMed Google Scholar). In the adult, very few excitatory synapses onto excitatory neurons are located on the dendritic shaft, and the vast majority of spines contain a single type 1 excitatory synapse (Harris et al., 1992Harris K.M. Jensen F.E. Tsao B. Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: Implications for the maturation of synaptic physiology and long-term potentiation.J. Neurosci. 1992; 12: 2685-2705Crossref PubMed Google Scholar, LeVay, 1973LeVay S. Synaptic patterns in the visual cortex of the cat and monkey. Electron microscopy of Golgi preparations.J. Comp. Neurol. 1973; 150: 53-85Crossref PubMed Google Scholar). Excitatory synapses that have been observed on the shaft are generally formed on the dendrites of inhibitory interneurons that are typically aspiny (Ahmed et al., 1997Ahmed B. Anderson J.C. Martin K.A. Nelson J.C. Map of the synapses onto layer 4 basket cells of the primary visual cortex of the cat.J. Comp. Neurol. 1997; 380: 230-242Crossref PubMed Scopus (109) Google Scholar, Bock et al., 2011Bock D.D. Lee W.C. Kerlin A.M. Andermann M.L. Hood G. Wetzel A.W. Yurgenson S. Soucy E.R. Kim H.S. Reid R.C. Network anatomy and in vivo physiology of visual cortical neurons.Nature. 2011; 471: 177-182Crossref PubMed Scopus (411) Google Scholar, Bopp et al., 2014Bopp R. Maçarico da Costa N. Kampa B.M. Martin K.A. Roth M.M. Pyramidal cells make specific connections onto smooth (GABAergic) neurons in mouse visual cortex.PLoS Biol. 2014; 12: e1001932Crossref PubMed Scopus (0) Google Scholar, Buhl et al., 1997Buhl E.H. Tamás G. Szilágyi T. Stricker C. Paulsen O. Somogyi P. Effect, number and location of synapses made by single pyramidal cells onto aspiny interneurones of cat visual cortex.J. Physiol. 1997; 500: 689-713Crossref PubMed Scopus (126) Google Scholar). The minority of inhibitory interneurons that contain spines are less spiny than pyramidal neurons (Kawaguchi et al., 2006Kawaguchi Y. Karube F. Kubota Y. Dendritic branch typing and spine expression patterns in cortical nonpyramidal cells.Cereb. Cortex. 2006; 16: 696-711Crossref PubMed Scopus (0) Google Scholar, Kuhlman and Huang, 2008Kuhlman S.J. Huang Z.J. High-resolution labeling and functional manipulation of specific neuron types in mouse brain by Cre-activated viral gene expression.PLoS ONE. 2008; 3: e2005Crossref PubMed Scopus (116) Google Scholar). Whether on excitatory neurons (Harris et al., 1992Harris K.M. Jensen F.E. Tsao B. Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: Implications for the maturation of synaptic physiology and long-term potentiation.J. Neurosci. 1992; 12: 2685-2705Crossref PubMed Google Scholar, LeVay, 1973LeVay S. Synaptic patterns in the visual cortex of the cat and monkey. Electron microscopy of Golgi preparations.J. Comp. Neurol. 1973; 150: 53-85Crossref PubMed Google Scholar) or on spiny inhibitory neurons, most spines contain a single type 1 excitatory synapse (Kawaguchi et al., 2006Kawaguchi Y. Karube F. Kubota Y. Dendritic branch typing and spine expression patterns in cortical nonpyramidal cells.Cereb. Cortex. 2006; 16: 696-711Crossref PubMed Scopus (0) Google Scholar, Kuhlman and Huang, 2008Kuhlman S.J. Huang Z.J. High-resolution labeling and functional manipulation of specific neuron types in mouse brain by Cre-activated viral gene expression.PLoS ONE. 2008; 3: e2005Crossref PubMed Scopus (116) Google Scholar). Spine size linearly correlates with PSD size and the number of presynaptic vesicles (Harris et al., 1992Harris K.M. Jensen F.E. Tsao B. Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: Implications for the maturation of synaptic physiology and long-term potentiation.J. Neurosci. 1992; 12: 2685-2705Crossref PubMed Google Scholar), as well as with synaptic strength (Asrican et al., 2007Asrican B. Lisman J. Otmakhov N. Synaptic strength of individual spines correlates with bound Ca2+-calmodulin-dependent kinase II.J. Neurosci. 2007; 27: 14007-14011Crossref PubMed Scopus (0) Google Scholar, Béïque et al., 2006Béïque J.C. Lin D.T. Kang M.G. Aizawa H. Takamiya K. Huganir R.L. Synapse-specific regulation of AMPA receptor function by PSD-95.Proc. Natl. Acad. Sci. USA. 2006; 103: 19535-19540Crossref PubMed Scopus (203) Google Scholar, Matsuzaki et al., 2001Matsuzaki M. Ellis-Davies G.C. Nemoto T. Miyashita Y. Iino M. Kasai H. Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons.Nat. Neurosci. 2001; 4: 1086-1092Crossref PubMed Scopus (917) Google Scholar, Noguchi et al., 2005Noguchi J. Matsuzaki M. Ellis-Davies G.C. Kasai H. Spine-neck geometry determines NMDA receptor-dependent Ca2+ signaling in dendrites.Neuron. 2005; 46: 609-622Abstract Full Text Full Text PDF PubMed Scopus (253) Google Scholar, Noguchi et al., 2011Noguchi J. Nagaoka A. Watanabe S. Ellis-Davies G.C. Kitamura K. Kano M. Matsuzaki M. Kasai H. In vivo two-photon uncaging of glutamate revealing the structure-function relationships of dendritic spines in the neocortex of adult mice.J. Physiol. 2011; 589: 2447-2457Crossref PubMed Scopus (71) Google Scholar, Zito et al., 2009Zito K. Scheuss V. Knott G. Hill T. Svoboda K. Rapid functional maturation of nascent dendritic spines.Neuron. 2009; 61: 247-258Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar). The close correspondence between spines and excitatory synaptic presence and strength is the basis for considering spines as good morphological surrogates for excitatory synapses. Spine density and size visualized through the use of sparse labeling methods such as the Golgi stain, injection of fluorescent dies, or transfection with genetically encoded fluorophore cell fills have been used to infer the locations of excitatory synapses in cultures, slices, and in vivo and as metrics to assess normal excitatory circuit health and development (reviewed in Rochefort and Konnerth, 2012Rochefort N.L. Konnerth A. Dendritic spines: From structure to in vivo function.EMBO Rep. 2012; 13: 699-708Crossref PubMed Scopus (95) Google Scholar). Dendritic protrusions are often grouped into 4 classes based on their morphologies: mushroom, thin, and stubby spines and filopodia (Peters and Kaiserman-Abramof, 1970Peters A. Kaiserman-Abramof I.R. The small pyramidal neuron of the rat cerebral cortex. The perikaryon, dendrites and spines.Am. J. Anat. 1970; 127: 321-355Crossref PubMed Scopus (579) Google Scholar). Mushroom shaped spines, defined by their characteristically large bulbous head and narrow neck, contain the largest excitatory synapses. Thin spines are smaller, lack the large bulbous head and thin neck, and contain smaller excitatory synapses. In the adult cortex and hippocampus, ∼25% of spines are mushroom shaped while >65% are thin shaped (Harris et al., 1992Harris K.M. Jensen F.E. Tsao B. Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: Implications for the maturation of synaptic physiology and long-term potentiation.J. Neurosci. 1992; 12: 2685-2705Crossref PubMed Google Scholar, Peters and Kaiserman-Abramof, 1970Peters A. Kaiserman-Abramof I.R. The small pyramidal neuron of the rat cerebral cortex. The perikaryon, dendrites and spines.Am. J. Anat. 1970; 127: 321-355Crossref PubMed Scopus (579) Google Scholar). Large mushroom spines may be close to the upper limits of synapse size and strength and therefore have little range for synaptic strengthening. New, thin spines, carrying small or immature synapses, would have a greater potential for strengthening and may therefore be indicative of the capacity for plasticity in the local circuit. This has led some to describe mushroom spines as memory spines and thin spines as learning spines (reviewed in Bourne and Harris, 2007Bourne J. Harris K.M. Do thin spines learn to be mushroom spines that remember?.Curr. Opin. Neurobiol. 2007; 17: 381-386Crossref PubMed Scopus (349) Google Scholar). The prevalence of thin spines declines during aging and cognitive deterioration (Dumitriu et al., 2010Dumitriu D. Hao J. Hara Y. Kaufmann J. Janssen W.G. Lou W. Rapp P.R. Morrison J.H. Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment.J. Neurosci. 2010; 30: 7507-7515Crossref PubMed Scopus (183) Google Scholar). However, manipulations that restore plasticity in older animals also increase the prevalence of thin spines (Hao et al., 2006Hao J. Rapp P.R. Leffler A.E. Leffler S.R. Janssen W.G. Lou W. McKay H. Roberts J.A. Wearne S.L. Hof P.R. Morrison J.H. Estrogen alters spine number and morphology in prefrontal cortex of aged female rhesus monkeys.J. Neurosci. 2006; 26: 2571-2578Crossref PubMed Scopus (162) Google Scholar). The third category of spines associated with excitatory synapse presence are the stubby spines. These spines are shorter and squatter than thin spines, lack a distinctive head and neck configuration, and are viewed as immature structures based on their prevalence during early postnatal development and relative scarcity in the mature brain (Harris et al., 1992Harris K.M. Jensen F.E. Tsao B. Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: Implications for the maturation of synaptic physiology and long-term potentiation.J. Neurosci. 1992; 12: 2685-2705Crossref PubMed Google Scholar). The fourth category of dendritic protrusions are filopodia, the smallest structures protruding from dendrites, often described as thin, hairlike structures. The immature filopodia or stubby shapes account for approximately 10% of spines in the adult (Fiala et al., 2002Fiala J.C. Allwardt B. Harris K.M. Dendritic spines do not split during hippocampal LTP or maturation.Nat. Neurosci. 2002; 5: 297-298Crossref PubMed Scopus (0) Google Scholar, Harris, 1999Harris K.M. Structure, development, and plasticity of dendritic spines.Curr. Opin. Neurobiol. 1999; 9: 343-348Crossref PubMed Scopus (362) Google Scholar, Harris et al., 1992Harris K.M. Jensen F.E. Tsao B. Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: Implications for the maturation of synaptic physiology and long-term potentiation.J. Neurosci. 1992; 12: 2685-2705Crossref PubMed Google Scholar, Peters and Kaiserman-Abramof, 1970Peters A. Kaiserman-Abramof I.R. The small pyramidal neuron of the rat cerebral cortex. The perikaryon, dendrites and spines.Am. J. Anat. 1970; 127: 321-355Crossref PubMed Scopus (579) Google Scholar). Many filopodia lack a clear type 1 synapse in EM micrographs (Arellano et al., 2007bArellano J.I. Espinosa A. Fairén A. Yuste R. DeFelipe J. Non-synaptic dendritic spines in neocortex.Neuroscience. 2007; 145: 464-469Crossref PubMed Scopus (0) Google Scholar), mostly due to the lack of a PSD, though they often present with synaptic characteristics such as a small cleft or a few synaptic vesicles (Fiala et al., 1998Fiala J.C. Feinberg M. Popov V. Harris K.M. Synaptogenesis via dendritic filopodia in developing hippocampal area CA1.J. Neurosci. 1998; 18: 8900-8911Crossref PubMed Google Scholar). Given their lack of clear type 1 synapses, one might think that filopodia should simply be excluded from spine counts that are used to represent synaptic density. However, this is not a trivial task due to the difficulty of distinguishing between spine morphological categories. Particularly difficult is drawing a clear distinction between filopodia and thin spines without the aid of EM. The resolution of light microscopy for the discrimination of small morphological differences is limited, especially along the z axis (Holtmaat et al., 2009Holtmaat A. Bonhoeffer T. Chow D.K. Chuckowree J. De Paola V. Hofer S.B. Hübener M. Keck T. Knott G. Lee W.C. et al.Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window.Nat. Protoc. 2009; 4: 1128-1144Crossref PubMed Scopus (393) Google Scholar, Sorra and Harris, 2000Sorra K.E. Harris K.M. Overview on the structure, composition, function, development, and plasticity of hippocampal dendritic spines.Hippocampus. 2000; 10: 501-511Crossref PubMed Scopus (0) Google Scholar). The ability to resolve a structure is dependent on the wavelength of light used to visualize that structure and the numerical aperture of the objective lens (Abbe diffraction limit), with axial resolution being worse than lateral resolution. In general terms, the shortest resolvable distance between two objects is roughly one-half of the wavelength of light used to illuminate the sample (NA∼1). Since the shortest wavelength of visible light is ∼400 nm, this limits the lateral r" @default.
• W2760721217 created "2017-10-06" @default.
• W2760721217 creator A5013691436 @default.
• W2760721217 creator A5014243012 @default.
• W2760721217 date "2017-09-01" @default.
• W2760721217 modified "2023-10-16" @default.
• W2760721217 title "Spine Dynamics: Are They All the Same?" @default.
• W2760721217 cites W1440335865 @default.
• W2760721217 cites W1487695731 @default.
• W2760721217 cites W1521767116 @default.
• W2760721217 cites W1535200077 @default.
• W2760721217 cites W1571022725 @default.
• W2760721217 cites W1572640432 @default.
• W2760721217 cites W1618384257 @default.
• W2760721217 cites W1624178692 @default.
• W2760721217 cites W1648575050 @default.
• W2760721217 cites W1655792606 @default.
• W2760721217 cites W1677457722 @default.
• W2760721217 cites W1716632673 @default.
• W2760721217 cites W1775494655 @default.
• W2760721217 cites W1798313689 @default.
• W2760721217 cites W1834463603 @default.
• W2760721217 cites W1855713874 @default.
• W2760721217 cites W1918894800 @default.
• W2760721217 cites W1943394565 @default.
• W2760721217 cites W1966155655 @default.
• W2760721217 cites W1969354341 @default.
• W2760721217 cites W1969379644 @default.
• W2760721217 cites W1976485053 @default.
• W2760721217 cites W1976958941 @default.
• W2760721217 cites W1979019425 @default.
• W2760721217 cites W1979755858 @default.
• W2760721217 cites W1980310343 @default.
• W2760721217 cites W1983284219 @default.
• W2760721217 cites W1983553517 @default.
• W2760721217 cites W1984341379 @default.
• W2760721217 cites W1984764602 @default.
• W2760721217 cites W1986246328 @default.
• W2760721217 cites W1993255478 @default.
• W2760721217 cites W1993788327 @default.
• W2760721217 cites W1996372033 @default.
• W2760721217 cites W1998708235 @default.
• W2760721217 cites W1999565685 @default.
• W2760721217 cites W2001528712 @default.
• W2760721217 cites W2003766648 @default.
• W2760721217 cites W2004569726 @default.
• W2760721217 cites W2007655140 @default.
• W2760721217 cites W2011497786 @default.
• W2760721217 cites W2011749906 @default.
• W2760721217 cites W2012010559 @default.
• W2760721217 cites W2012529293 @default.
• W2760721217 cites W2014163893 @default.
• W2760721217 cites W2016756702 @default.
• W2760721217 cites W2016941370 @default.
• W2760721217 cites W2017613746 @default.
• W2760721217 cites W2019543624 @default.
• W2760721217 cites W2022235653 @default.
• W2760721217 cites W2024694517 @default.
• W2760721217 cites W2029015906 @default.
• W2760721217 cites W2032579724 @default.
• W2760721217 cites W2037969635 @default.
• W2760721217 cites W2039450535 @default.
• W2760721217 cites W2039508969 @default.
• W2760721217 cites W2040733551 @default.
• W2760721217 cites W2041373424 @default.
• W2760721217 cites W2041963605 @default.
• W2760721217 cites W2043430884 @default.
• W2760721217 cites W2053666202 @default.
• W2760721217 cites W2054797412 @default.
• W2760721217 cites W2056431599 @default.
• W2760721217 cites W2059288735 @default.
• W2760721217 cites W2060584787 @default.
• W2760721217 cites W2061464631 @default.
• W2760721217 cites W2069118261 @default.
• W2760721217 cites W2069863147 @default.
• W2760721217 cites W2070524933 @default.
• W2760721217 cites W2071318481 @default.
• W2760721217 cites W2073291441 @default.
• W2760721217 cites W2073577336 @default.
• W2760721217 cites W2074623278 @default.
• W2760721217 cites W2075588276 @default.
• W2760721217 cites W2075621633 @default.
• W2760721217 cites W2077081354 @default.
• W2760721217 cites W2077706363 @default.
• W2760721217 cites W2080351494 @default.
• W2760721217 cites W2082900258 @default.
• W2760721217 cites W2083060092 @default.
• W2760721217 cites W2087824537 @default.
• W2760721217 cites W2088239473 @default.
• W2760721217 cites W2088321899 @default.
• W2760721217 cites W2088446997 @default.
• W2760721217 cites W2090043895 @default.
• W2760721217 cites W2090319528 @default.
• W2760721217 cites W2092326283 @default.
• W2760721217 cites W2093573816 @default.
• W2760721217 cites W2094455233 @default.
• W2760721217 cites W2095300775 @default.
• W2760721217 cites W2098917165 @default.

• next