Aberrant Dendritic Excitability: A Common Pathophysiology in CNS Disorders Affecting Memory?

被引:17
作者
Nestor, Michael W. [1 ]
Hoffman, Dax A. [1 ]
机构
[1] NICHD, Mol Neurophysiol & Biophys Unit, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA
关键词
Dendritic excitability; Autism; Fragile-X; Alzheimer's disease; A-type K+ channel; Hippocampus; LONG-TERM POTENTIATION; TIMING-DEPENDENT PLASTICITY; CELL-ADHESION MOLECULE; AMYLOID-BETA PEPTIDE; MOUSE MODEL; SYNAPTIC PLASTICITY; MENTAL-RETARDATION; TRANSGENIC MICE; RETT-SYNDROME; ALZHEIMERS-DISEASE;
D O I
10.1007/s12035-012-8265-x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Discovering the etiology of pathophysiologies and aberrant behavior in many central nervous system (CNS) disorders has proven elusive because susceptibility to these diseases can be a product of multiple factors such as genetics, epigenetics, and environment. Advances in molecular biology and wide-scale genomics have shown that a large heterogeneity of genetic mutations are potentially responsible for the neuronal pathologies and dysfunctional behaviors seen in CNS disorders. Despite this seemingly complex array of genetic and physiological factors, many disorders of the CNS converge on common dysfunctions in memory. In this review, we propose that mechanisms underlying the development of many CNS disorders may share an underlying cause involving abnormal dendritic integration of synaptic signals. Through understanding the relationship between molecular genetics and dendritic computation, future research may uncover important links between neuronal physiology at the cellular level and higher-order circuit and network abnormalities observed in CNS disorders, and their subsequent affect on memory.
引用
收藏
页码:478 / 487
页数:10
相关论文
共 117 条
[1]   SELECTIVE DENDRITIC ALTERATIONS IN THE CORTEX OF RETT-SYNDROME [J].
ARMSTRONG, D ;
DUNN, JK ;
ANTALFFY, B ;
TRIVEDI, R .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1995, 54 (02) :195-201
[2]   Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome [J].
Asaka, Y ;
Jugloff, DGM ;
Zhang, LA ;
Eubanks, JH ;
Fitzsimonds, RM .
NEUROBIOLOGY OF DISEASE, 2006, 21 (01) :217-227
[3]   Role of tau protein in both physiological and pathological conditions [J].
Avila, J ;
Lucas, JJ ;
Pérez, M ;
Hernández, F .
PHYSIOLOGICAL REVIEWS, 2004, 84 (02) :361-384
[4]   From mRNP trafficking to spine dysmorphogenesis: The roots of fragile X syndrome [J].
Bagni, C ;
Greenough, WT .
NATURE REVIEWS NEUROSCIENCE, 2005, 6 (05) :376-387
[5]   Prevalence of disorders of the autism spectrum in a population cohort of children in South Thames: the Special Needs and Autism Project (SNAP) [J].
Baird, Gillian ;
Simonoff, Emily ;
Pickles, Andrew ;
Chandler, Susie ;
Loucas, Tom ;
Meldrum, David ;
Charman, Tony .
LANCET, 2006, 368 (9531) :210-215
[6]   RETRACTED: Enhanced Polyubiquitination of Shank3 and NMDA Receptor in a Mouse Model of Autism (Retracted article. See vol. 152, pg. 367, 2013) [J].
Bangash, M. Ali ;
Park, Joo Min ;
Melnikova, Tatiana ;
Wang, Dehua ;
Jeon, Soo Kyeong ;
Lee, Deidre ;
Syeda, Sbaa ;
Kim, Juno ;
Kouser, Mehreen ;
Schwartz, Joshua ;
Cui, Yiyuan ;
Zhao, Xia ;
Speed, Haley E. ;
Kee, Sara E. ;
Tu, Jian Cheng ;
Hu, Jia-Hua ;
Petralia, Ronald S. ;
Linden, David J. ;
Powell, Craig M. ;
Savonenko, Alena ;
Xiao, Bo ;
Worley, Paul F. .
CELL, 2011, 145 (05) :758-772
[7]   The mGIuR theory of fragile X mental retardation [J].
Bear, MF ;
Huber, KM ;
Warren, ST .
TRENDS IN NEUROSCIENCES, 2004, 27 (07) :370-377
[8]   Widespread Changes in Dendritic and Axonal Morphology in Mecp2-Mutant Mouse Models of Rett Syndrome: Evidence for Disruption of Neuronal Networks [J].
Belichenko, Pavel V. ;
Wright, Elena E. ;
Belichenko, Nadia P. ;
Masliah, Eliezer ;
Li, Hong Hua ;
Mobley, William C. ;
Francke, Uta .
JOURNAL OF COMPARATIVE NEUROLOGY, 2009, 514 (03) :240-258
[9]   Acquired dendritic channelopathy in temporal lobe epilepsy [J].
Bernard, C ;
Anderson, A ;
Becker, A ;
Poolos, NP ;
Beck, H ;
Johnston, D .
SCIENCE, 2004, 305 (5683) :532-535
[10]   Increased anxiety-like behavior in mice lacking the inhibitory synapse cell adhesion molecule neuroligin 2 [J].
Blundell, J. ;
Tabuchi, K. ;
Bolliger, M. F. ;
Blaiss, C. A. ;
Brose, N. ;
Liu, X. ;
Sudhof, T. C. ;
Powell, C. M. .
GENES BRAIN AND BEHAVIOR, 2009, 8 (01) :114-126