G Model NSL-31187; No. of Pages 3
ARTICLE IN PRESS Neuroscience Letters xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet
Preface
Dendritic spine dysgenesis: An emerging concept in neuropsychiatric disease
Neurons are elegant in form and function – comprised of a cell body, dendritic trees, and axonal projections. Neuronal structure appears simple, yet these electrically excitable cells manifest a complexity of function that has intimidated and inspired generations of scientists. Many have wondered about the purpose of the nervous system: is the nervous system a tangible medium for the human psyche, a biological place for all our musings and moods? Indeed, our most compelling evidence for understanding abnormal conditions of the mind has been through empirical study of neuroanatomy and physiology. The oldest and perhaps best clue into how neural networks function emerge from visual observations of dendritic spines – microscopic protrusions on a neuron’s dendritic branches. Santiago Ramon y Cajal first described dendritic spines on neurons in the cerebellum in the late 19th century [6,11,23]. Using the Golgistaining method for visualizing fine morphological processes, Cajal described the surface of Purkinje neurons in the cerebellum as having “espina” or short spines [24]. His publications were the first to name these microscopic structures as “dendritic spines” and he speculated that these dendritic spines would be the main contact point between axons and dendrites [11,12,31] (Fig. 1). Moreover, Cajal proposed that dendritic spine structures contribute to the generation of neuronal activity and have a role in the process of learning [30]. These impressive speculations during Cajal’s lifetime now form the basis for much of what neuroscientists study today. Approximately 90% of all excitatory synapses in the mammalian nervous system occur on dendritic spines [16]. Spines are primarily comprised of filamentous (F)-actin and associated with neurons that receive convergent input, including hippocampal neurons, pyramidal neurons in the motor cortex, Purkinje neurons in the cerebellum, and many other regions of the CNS [13,17,25,26]. In the normal nervous system, dendritic spines have been of greatest interest to the field of learning and memory, particularly within the context of the well-accepted synaptic model of long-term potentiation (LTP) [19]. LTP is defined as a local increase in synaptic efficacy between two neurons following coincident and synchronous activity. In vivo, LTP can persist for days, which is an observation that has supported LTP as a mechanism for maintaining neural circuits and memory. Dendritic spine formation, development, and maturation occur in the later phases of LTP, which involves the activation of a number of downstream kinases including PKA, PKC, and
extracellular signal-related kinase (ERK) [5,20]. To maintain LTP and increased synaptic strength through dendritic spines, actin polymerization and stabilization are crucial. Pharmacological inhibition of actin polymerization with lactriculins or cytochalasins disrupts activity-dependent maturation of dendritic spines and blocks long-term LTP [7,10]. Neurotrophins, such as BDNF, are involved in translation-dependent long-term memory as well as the development of dendritic spines [1,28]. Importantly, dendritic spines can directly regulate synaptic function through structural remodeling [9]. While the dendritic spine head surface acts as an interface for presynaptic input, the spine neck acts as a “diffusion gate” that limits the movement of cations and other molecules, e.g., calcium, into the main dendrite branch. In this manner, dendritic spine conformational changes can directly affect local synaptic function in response to activity [32]. Note that larger, more mature dendritic spines with mushroom-shaped morphologies are associated with stronger synapses and the formation of memory [4]. Interestingly, dendritic spines work as discrete compartments on neurons that can isolate and integrate electrical information at the local, synaptic level. This compartmentalized gating property of spines is thought to be the mechanism that grants a single neuron its incredible computational power [2,3,27,33]. Overall, dendritic spine structure contributes to synaptic functionand are an inextricable component in our quest for understanding the depths of cognitive function. Since we expect that abnormalities of mind will be reflected in abnormalities of the nervous system, it is not surprising that dendritic spine dysgenesis (i.e., spine malformation) is associated with a wide spectrum of neuropsychiatric diseases [8,14,15,18,21,22,26]. However, the role of dendritic spines in neuropsychiatric diseases is not firmly understood. In this Special Issue of Neuroscience Letters, a range of neuropsychiatric diseases is reviewed in the context of dendritic spine dysgenesis. One in four families in the United States have at least one member currently suffering with a mental or behavioral disorder associated with a neuropsychiatric disease [29]. The burden on individuals and caregivers are immense given the economic difficulties and emotional reactions to the illness, and the stress of coping with disrupted behavior and daily routine. There are no cure-alls for neuropsychiatric diseases. Thus, there is a significant medical need for deeper insight into the neurological basis for human thought and behavior. Advancements in molecular and genetic approaches to restore neurological dysfunction could
http://dx.doi.org/10.1016/j.neulet.2015.03.009 0304-3940/Published by Elsevier Ireland Ltd.
Please cite this article in press as: A.M. Tan, Dendritic spine dysgenesis: An emerging concept in neuropsychiatric disease, Neurosci. Lett. (2015), http://dx.doi.org/10.1016/j.neulet.2015.03.009
G Model NSL-31187; No. of Pages 3
ARTICLE IN PRESS Preface / Neuroscience Letters xxx (2015) xxx–xxx
2
Fig. 1. (A) Original drawing by Cajal showing pyramidal cells of rabbit cerebral cortex (1896, black ink and pencil). Dendritic spines are clearly depicted. Cajal Legacy. Instituto Cajal (CSIC). Madrid (Spain). (B–D) Cajal’s histological use of the Golgi-method created beautiful images of cortical neurons: (B) pyramidal cell branches in the motor cortex, (C) apical branch of a pyramidal cell, and (D) basilar dendritic branch [12].
provide promising avenues for addressing abnormal psychiatric conditions.
References [1] M. Alonso, J.H. Medina, L. Pozzo-Miller, ERK1/2 activation is necessary for BDNF to increase dendritic spine density in hippocampal CA1 pyramidal neurons, Learn. Mem. 11 (2004) 172–178. [2] R. Araya, K.B. Eisenthal, R. Yuste, Dendritic spines linearize the summation of excitatory potentials, Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 18799–18804. [3] R. Araya, J. Jiang, K.B. Eisenthal, R. Yuste, The spine neck filters membrane potentials, Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 17961–17966. [4] J. Bourne, K.M. Harris, Do thin spines learn to be mushroom spines that remember? Curr. Opin. Neurobiol. 17 (2007) 381–386. [5] C.R. Bramham, Local protein synthesis, actin dynamics, and LTP consolidation, Curr. Opin. Neurobiol. 18 (2008) 524–531. [6] B. Calabrese, M.S. Wilson, S. Halpain, Development and regulation of dendritic spine synapses, Physiology (Bethesda) 21 (2006) 38–47. [7] H.J. Carlisle, M.B. Kennedy, Spine architecture and synaptic plasticity, Trends Neurosci. 28 (2005) 182–187. [8] C.A. Chapleau, J.L. Larimore, A. Theibert, L. Pozzo-Miller, Modulation of dendritic spine development and plasticity by BDNF and vesicular trafficking: fundamental roles in neurodevelopmental disorders associated with mental retardation and autism, J. Neurodev. Disord. 1 (2009) 185–196. [9] E. Fifkova, A possible mechanism of morphometric changes in dendritic spines induced by stimulation, Cell. Mol. Neurobiol. 5 (1985) 47–63. [10] Y. Fukazawa, Y. Saitoh, F. Ozawa, Y. Ohta, K. Mizuno, K. Inokuchi, Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo, Neuron 38 (2003) 447–460. [11] P. Garcia-Lopez, V. Garcia-Marin, M. Freire, The discovery of dendritic spines by Cajal in 1888 and its relevance in the present neuroscience, Prog. Neurobiol. 83 (2007) 110–130. [12] P. Garcia-Lopez, V. Garcia-Marin, M. Freire, Dendritic spines and development: towards a unifying model of spinogenesis – a present day review of Cajal’s histological slides and drawings, Neural Plast. 2010 (2010) 769207. [13] A. Gazzaley, S. Kay, D.L. Benson, Dendritic spine plasticity in hippocampus, Neuroscience 111 (2002) 853–862.
[14] A.B. Hains, M.A. Vu, P.K. Maciejewski, C.H. van Dyck, M. Gottron, A.F. Arnsten, Inhibition of protein kinase C signaling protects prefrontal cortex dendritic spines and cognition from the effects of chronic stress, Proc. Natl. Acad. Sci. U. S. A. 106 (2009) 17957–17962. [15] S. Halpain, K. Spencer, S. Graber, Dynamics and pathology of dendritic spines, Prog. Brain Res. 147 (2005) 29–37. [16] K.M. Harris, S.B. Kater, Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function, Annu. Rev. Neurosci. 17 (1994) 341–371. [17] B.G. Kim, H.N. Dai, M. McAtee, S. Vicini, B.S. Bregman, Remodeling of synaptic structures in the motor cortex following spinal cord injury, Exp. Neurol. 198 (2006) 401–415. [18] Z.H. Liu, D.M. Chuang, C.B. Smith, Lithium ameliorates phenotypic deficits in a mouse model of fragile X syndrome, Int. J. Neuropsychopharmacol. 14 (2011) 618–630. [19] R.C. Malenka, The long-term potential of LTP, Nat. Rev. Neurosci. 4 (2003) 923–926. [20] M. Matsuzaki, N. Honkura, G.C. Ellis-Davies, H. Kasai, Structural basis of long-term potentiation in single dendritic spines, Nature 429 (2004) 761–766. [21] P.J. Mulholland, L.J. Chandler, The thorny side of addiction: adaptive plasticity and dendritic spines, Sci. World J. 7 (2007) 9–21. [22] D.P. Purpura, Dendritic spine “dysgenesis” and mental retardation, Science 186 (1974) 1126–1128. [23] S. Ramon y Cajal, Estructura de los centros nerviosos de las aves, Rev. Trim. Histol. Norm. Pat. 1 (1888) 1–10. ˜ [24] S. Ramon y Cajal, Las espinas colaterales de las células del cerebro tenidas por el azul de metileno, Rev. Trimest. Micrograf. Madrid 1 (1896) 123–136. [25] F. Santamaria, S. Wils, E. De Schutter, G.J. Augustine, Anomalous diffusion in Purkinje cell dendrites caused by spines, Neuron 52 (2006) 635–648. [26] A.M. Tan, S.G. Waxman, Spinal cord injury, dendritic spine remodeling, and spinal memory mechanisms, Exp. Neurol. 235 (2012) 142–151. [27] D. Tsay, R. Yuste, On the electrical function of dendritic spines, Trends Neurosci. 27 (2004) 77–83. [28] W.J. Tyler, L. Pozzo-Miller, Miniature synaptic transmission and BDNF modulate dendritic spine growth and form in rat CA1 neurones, J. Physiol. 553 (2003) 497–509. [29] World-Health-Organization, Investing in Mental Health, WHO Library Cataloguing-in-Publication Data, 2003.
Please cite this article in press as: A.M. Tan, Dendritic spine dysgenesis: An emerging concept in neuropsychiatric disease, Neurosci. Lett. (2015), http://dx.doi.org/10.1016/j.neulet.2015.03.009
G Model NSL-31187; No. of Pages 3
ARTICLE IN PRESS Preface / Neuroscience Letters xxx (2015) xxx–xxx
[30] R. Yuste, T. Bonhoeffer, Morphological changes in dendritic spines associated with long-term synaptic plasticity, Annu. Rev. Neurosci. 24 (2001) 1071–1089. [31] R. Yuste, A. Majewska, On the function of dendritic spines, Neuroscientist 7 (2001) 387–395. [32] R. Yuste, A. Majewska, K. Holthoff, From form to function: calcium compartmentalization in dendritic spines, Nat. Neurosci. 3 (2000) 653–659.
3
[33] R. Yuste, R. Urban, Dendritic spines and linear networks, J. Physiol. Paris 98 (2004) 479–486.
Andrew M. Tan Available online xxx
Please cite this article in press as: A.M. Tan, Dendritic spine dysgenesis: An emerging concept in neuropsychiatric disease, Neurosci. Lett. (2015), http://dx.doi.org/10.1016/j.neulet.2015.03.009
ARTICLE IN PRESS Neuroscience Letters xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet
Preface
Dendritic spine dysgenesis: An emerging concept in neuropsychiatric disease
Neurons are elegant in form and function – comprised of a cell body, dendritic trees, and axonal projections. Neuronal structure appears simple, yet these electrically excitable cells manifest a complexity of function that has intimidated and inspired generations of scientists. Many have wondered about the purpose of the nervous system: is the nervous system a tangible medium for the human psyche, a biological place for all our musings and moods? Indeed, our most compelling evidence for understanding abnormal conditions of the mind has been through empirical study of neuroanatomy and physiology. The oldest and perhaps best clue into how neural networks function emerge from visual observations of dendritic spines – microscopic protrusions on a neuron’s dendritic branches. Santiago Ramon y Cajal first described dendritic spines on neurons in the cerebellum in the late 19th century [6,11,23]. Using the Golgistaining method for visualizing fine morphological processes, Cajal described the surface of Purkinje neurons in the cerebellum as having “espina” or short spines [24]. His publications were the first to name these microscopic structures as “dendritic spines” and he speculated that these dendritic spines would be the main contact point between axons and dendrites [11,12,31] (Fig. 1). Moreover, Cajal proposed that dendritic spine structures contribute to the generation of neuronal activity and have a role in the process of learning [30]. These impressive speculations during Cajal’s lifetime now form the basis for much of what neuroscientists study today. Approximately 90% of all excitatory synapses in the mammalian nervous system occur on dendritic spines [16]. Spines are primarily comprised of filamentous (F)-actin and associated with neurons that receive convergent input, including hippocampal neurons, pyramidal neurons in the motor cortex, Purkinje neurons in the cerebellum, and many other regions of the CNS [13,17,25,26]. In the normal nervous system, dendritic spines have been of greatest interest to the field of learning and memory, particularly within the context of the well-accepted synaptic model of long-term potentiation (LTP) [19]. LTP is defined as a local increase in synaptic efficacy between two neurons following coincident and synchronous activity. In vivo, LTP can persist for days, which is an observation that has supported LTP as a mechanism for maintaining neural circuits and memory. Dendritic spine formation, development, and maturation occur in the later phases of LTP, which involves the activation of a number of downstream kinases including PKA, PKC, and
extracellular signal-related kinase (ERK) [5,20]. To maintain LTP and increased synaptic strength through dendritic spines, actin polymerization and stabilization are crucial. Pharmacological inhibition of actin polymerization with lactriculins or cytochalasins disrupts activity-dependent maturation of dendritic spines and blocks long-term LTP [7,10]. Neurotrophins, such as BDNF, are involved in translation-dependent long-term memory as well as the development of dendritic spines [1,28]. Importantly, dendritic spines can directly regulate synaptic function through structural remodeling [9]. While the dendritic spine head surface acts as an interface for presynaptic input, the spine neck acts as a “diffusion gate” that limits the movement of cations and other molecules, e.g., calcium, into the main dendrite branch. In this manner, dendritic spine conformational changes can directly affect local synaptic function in response to activity [32]. Note that larger, more mature dendritic spines with mushroom-shaped morphologies are associated with stronger synapses and the formation of memory [4]. Interestingly, dendritic spines work as discrete compartments on neurons that can isolate and integrate electrical information at the local, synaptic level. This compartmentalized gating property of spines is thought to be the mechanism that grants a single neuron its incredible computational power [2,3,27,33]. Overall, dendritic spine structure contributes to synaptic functionand are an inextricable component in our quest for understanding the depths of cognitive function. Since we expect that abnormalities of mind will be reflected in abnormalities of the nervous system, it is not surprising that dendritic spine dysgenesis (i.e., spine malformation) is associated with a wide spectrum of neuropsychiatric diseases [8,14,15,18,21,22,26]. However, the role of dendritic spines in neuropsychiatric diseases is not firmly understood. In this Special Issue of Neuroscience Letters, a range of neuropsychiatric diseases is reviewed in the context of dendritic spine dysgenesis. One in four families in the United States have at least one member currently suffering with a mental or behavioral disorder associated with a neuropsychiatric disease [29]. The burden on individuals and caregivers are immense given the economic difficulties and emotional reactions to the illness, and the stress of coping with disrupted behavior and daily routine. There are no cure-alls for neuropsychiatric diseases. Thus, there is a significant medical need for deeper insight into the neurological basis for human thought and behavior. Advancements in molecular and genetic approaches to restore neurological dysfunction could
http://dx.doi.org/10.1016/j.neulet.2015.03.009 0304-3940/Published by Elsevier Ireland Ltd.
Please cite this article in press as: A.M. Tan, Dendritic spine dysgenesis: An emerging concept in neuropsychiatric disease, Neurosci. Lett. (2015), http://dx.doi.org/10.1016/j.neulet.2015.03.009
G Model NSL-31187; No. of Pages 3
ARTICLE IN PRESS Preface / Neuroscience Letters xxx (2015) xxx–xxx
2
Fig. 1. (A) Original drawing by Cajal showing pyramidal cells of rabbit cerebral cortex (1896, black ink and pencil). Dendritic spines are clearly depicted. Cajal Legacy. Instituto Cajal (CSIC). Madrid (Spain). (B–D) Cajal’s histological use of the Golgi-method created beautiful images of cortical neurons: (B) pyramidal cell branches in the motor cortex, (C) apical branch of a pyramidal cell, and (D) basilar dendritic branch [12].
provide promising avenues for addressing abnormal psychiatric conditions.
References [1] M. Alonso, J.H. Medina, L. Pozzo-Miller, ERK1/2 activation is necessary for BDNF to increase dendritic spine density in hippocampal CA1 pyramidal neurons, Learn. Mem. 11 (2004) 172–178. [2] R. Araya, K.B. Eisenthal, R. Yuste, Dendritic spines linearize the summation of excitatory potentials, Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 18799–18804. [3] R. Araya, J. Jiang, K.B. Eisenthal, R. Yuste, The spine neck filters membrane potentials, Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 17961–17966. [4] J. Bourne, K.M. Harris, Do thin spines learn to be mushroom spines that remember? Curr. Opin. Neurobiol. 17 (2007) 381–386. [5] C.R. Bramham, Local protein synthesis, actin dynamics, and LTP consolidation, Curr. Opin. Neurobiol. 18 (2008) 524–531. [6] B. Calabrese, M.S. Wilson, S. Halpain, Development and regulation of dendritic spine synapses, Physiology (Bethesda) 21 (2006) 38–47. [7] H.J. Carlisle, M.B. Kennedy, Spine architecture and synaptic plasticity, Trends Neurosci. 28 (2005) 182–187. [8] C.A. Chapleau, J.L. Larimore, A. Theibert, L. Pozzo-Miller, Modulation of dendritic spine development and plasticity by BDNF and vesicular trafficking: fundamental roles in neurodevelopmental disorders associated with mental retardation and autism, J. Neurodev. Disord. 1 (2009) 185–196. [9] E. Fifkova, A possible mechanism of morphometric changes in dendritic spines induced by stimulation, Cell. Mol. Neurobiol. 5 (1985) 47–63. [10] Y. Fukazawa, Y. Saitoh, F. Ozawa, Y. Ohta, K. Mizuno, K. Inokuchi, Hippocampal LTP is accompanied by enhanced F-actin content within the dendritic spine that is essential for late LTP maintenance in vivo, Neuron 38 (2003) 447–460. [11] P. Garcia-Lopez, V. Garcia-Marin, M. Freire, The discovery of dendritic spines by Cajal in 1888 and its relevance in the present neuroscience, Prog. Neurobiol. 83 (2007) 110–130. [12] P. Garcia-Lopez, V. Garcia-Marin, M. Freire, Dendritic spines and development: towards a unifying model of spinogenesis – a present day review of Cajal’s histological slides and drawings, Neural Plast. 2010 (2010) 769207. [13] A. Gazzaley, S. Kay, D.L. Benson, Dendritic spine plasticity in hippocampus, Neuroscience 111 (2002) 853–862.
[14] A.B. Hains, M.A. Vu, P.K. Maciejewski, C.H. van Dyck, M. Gottron, A.F. Arnsten, Inhibition of protein kinase C signaling protects prefrontal cortex dendritic spines and cognition from the effects of chronic stress, Proc. Natl. Acad. Sci. U. S. A. 106 (2009) 17957–17962. [15] S. Halpain, K. Spencer, S. Graber, Dynamics and pathology of dendritic spines, Prog. Brain Res. 147 (2005) 29–37. [16] K.M. Harris, S.B. Kater, Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function, Annu. Rev. Neurosci. 17 (1994) 341–371. [17] B.G. Kim, H.N. Dai, M. McAtee, S. Vicini, B.S. Bregman, Remodeling of synaptic structures in the motor cortex following spinal cord injury, Exp. Neurol. 198 (2006) 401–415. [18] Z.H. Liu, D.M. Chuang, C.B. Smith, Lithium ameliorates phenotypic deficits in a mouse model of fragile X syndrome, Int. J. Neuropsychopharmacol. 14 (2011) 618–630. [19] R.C. Malenka, The long-term potential of LTP, Nat. Rev. Neurosci. 4 (2003) 923–926. [20] M. Matsuzaki, N. Honkura, G.C. Ellis-Davies, H. Kasai, Structural basis of long-term potentiation in single dendritic spines, Nature 429 (2004) 761–766. [21] P.J. Mulholland, L.J. Chandler, The thorny side of addiction: adaptive plasticity and dendritic spines, Sci. World J. 7 (2007) 9–21. [22] D.P. Purpura, Dendritic spine “dysgenesis” and mental retardation, Science 186 (1974) 1126–1128. [23] S. Ramon y Cajal, Estructura de los centros nerviosos de las aves, Rev. Trim. Histol. Norm. Pat. 1 (1888) 1–10. ˜ [24] S. Ramon y Cajal, Las espinas colaterales de las células del cerebro tenidas por el azul de metileno, Rev. Trimest. Micrograf. Madrid 1 (1896) 123–136. [25] F. Santamaria, S. Wils, E. De Schutter, G.J. Augustine, Anomalous diffusion in Purkinje cell dendrites caused by spines, Neuron 52 (2006) 635–648. [26] A.M. Tan, S.G. Waxman, Spinal cord injury, dendritic spine remodeling, and spinal memory mechanisms, Exp. Neurol. 235 (2012) 142–151. [27] D. Tsay, R. Yuste, On the electrical function of dendritic spines, Trends Neurosci. 27 (2004) 77–83. [28] W.J. Tyler, L. Pozzo-Miller, Miniature synaptic transmission and BDNF modulate dendritic spine growth and form in rat CA1 neurones, J. Physiol. 553 (2003) 497–509. [29] World-Health-Organization, Investing in Mental Health, WHO Library Cataloguing-in-Publication Data, 2003.
Please cite this article in press as: A.M. Tan, Dendritic spine dysgenesis: An emerging concept in neuropsychiatric disease, Neurosci. Lett. (2015), http://dx.doi.org/10.1016/j.neulet.2015.03.009
G Model NSL-31187; No. of Pages 3
ARTICLE IN PRESS Preface / Neuroscience Letters xxx (2015) xxx–xxx
[30] R. Yuste, T. Bonhoeffer, Morphological changes in dendritic spines associated with long-term synaptic plasticity, Annu. Rev. Neurosci. 24 (2001) 1071–1089. [31] R. Yuste, A. Majewska, On the function of dendritic spines, Neuroscientist 7 (2001) 387–395. [32] R. Yuste, A. Majewska, K. Holthoff, From form to function: calcium compartmentalization in dendritic spines, Nat. Neurosci. 3 (2000) 653–659.
3
[33] R. Yuste, R. Urban, Dendritic spines and linear networks, J. Physiol. Paris 98 (2004) 479–486.
Andrew M. Tan Available online xxx
Please cite this article in press as: A.M. Tan, Dendritic spine dysgenesis: An emerging concept in neuropsychiatric disease, Neurosci. Lett. (2015), http://dx.doi.org/10.1016/j.neulet.2015.03.009
