Alterations of Neocortical Pyramidal Neurons: Turning Points in the Genesis of Mental Retardation

Pyramidal neurons (PNs) represent the majority of neocortical cells and their involvement in cognitive functions is decisive. Therefore, they are the most obvious target of developmental disorders characterized by mental retardation. Genetic and non-genetic forms of intellectual disability share a few basic pathogenetic signatures that result in the anomalous function of PNs. Here, we review the key mechanisms impairing these neurons and their participation in the cortical network, with special focus on experimental models of fetal exposure to alcohol. Due to the heterogeneity of PNs, some alterations affect selectively a given cell population, which may also differ depending on the considered pathology. These specific features open new possibilities for the interpretation of cognitive defects observed in mental retardation syndromes, as well as for novel therapeutic interventions.

[1]  Alberto Granato,et al.  Effects of early ethanol exposure on dendrite growth of cortical pyramidal neurons: inferences from a computational model. , 2003, Brain research. Developmental brain research.

[2]  Y. Miyashita,et al.  Reversal of Interlaminar Signal Between Sensory and Memory Processing in Monkey Temporal Cortex , 2011, Science.

[3]  G. Shepherd,et al.  Emerging rules for the distributions of active dendritic conductances , 2002, Nature Reviews Neuroscience.

[4]  C. Valenzuela,et al.  Low Concentrations of Alcohol Inhibit BDNF-Dependent GABAergic Plasticity via L-type Ca2+ Channel Inhibition in Developing CA3 Hippocampal Pyramidal Neurons , 2010, The Journal of Neuroscience.

[5]  I. Weiler,et al.  Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[6]  B. Sakmann,et al.  Dendritic Spikes in Apical Dendrites of Neocortical Layer 2/3 Pyramidal Neurons , 2007, The Journal of Neuroscience.

[7]  V. Narayanan,et al.  Isoform-Specific Toxicity of Mecp2 in Postmitotic Neurons: Suppression of Neurotoxicity by FoxG1 , 2012, The Journal of Neuroscience.

[8]  M. Miller,et al.  Migration of cortical neurons is altered by gestational exposure to ethanol. , 1993, Alcoholism, clinical and experimental research.

[9]  E. Masliah,et al.  Widespread changes in dendritic and axonal morphology in Mecp2‐mutant mouse models of rett syndrome: Evidence for disruption of neuronal networks , 2009, The Journal of comparative neurology.

[10]  J. Olney,et al.  Glutamate and GABA receptor dysfunction in the fetal alcohol syndrome , 2009, Neurotoxicity Research.

[11]  G. Elston.  Cortex, cognition and the cell: new insights into the pyramidal neuron and prefrontal function. , 2003, Cerebral cortex.

[12]  J. Gibson,et al.  Imbalance of neocortical excitation and inhibition and altered UP states reflect network hyperexcitability in the mouse model of fragile X syndrome. , 2008, Journal of neurophysiology.

[13]  A. Ruiz-Marcos,et al.  Pyramidal cortical cell morphology studied by multivariate analysis: effects of neonatal thyroidectomy, ageing and thyroxine-substitution therapy. , 1987, Brain research.

[14]  J. Olney,et al.  Ethanol-induced apoptotic neurodegeneration in the developing C57BL/6 mouse brain. , 2002, Brain research. Developmental brain research.

[15]  X. Estivill,et al.  Alterations of neocortical pyramidal cell phenotype in the Ts65Dn mouse model of Down syndrome: effects of environmental enrichment. , 2003, Cerebral cortex.

[16]  K. Svoboda,et al.  Interdigitated Paralemniscal and Lemniscal Pathways in the Mouse Barrel Cortex , 2006, PLoS biology.

[17]  A. Granato.  Altered organization of cortical interneurons in rats exposed to ethanol during neonatal life , 2006, Brain Research.

[18]  Paul Nurse,et al.  Cell Division Intersects with Cell Geometry , 2010, Cell.

[19]  Jessica A. Cardin,et al.  Neocortical Interneurons: From Diversity, Strength , 2010, Cell.

[20]  A. Polsky,et al.  Synaptic Integration in Tuft Dendrites of Layer 5 Pyramidal Neurons: A New Unifying Principle , 2009, Science.

[21]  M. E. Charness,et al.  Retracted: Ethanol disrupts axon outgrowth stimulated by netrin‐1, GDNF, and L1 by blocking their convergent activation of Src family kinase signaling , 2012, Journal of neurochemistry.

[22]  A. Medina.  Fetal Alcohol Spectrum Disorders and Abnormal Neuronal Plasticity , 2011, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[23]  G. Fishell,et al.  A disinhibitory circuit mediates motor integration in the somatosensory cortex , 2013, Nature Neuroscience.

[24]  M. Larkum.  A cellular mechanism for cortical associations: an organizing principle for the cerebral cortex , 2013, Trends in Neurosciences.

[25]  B W Connors,et al.  Backward cortical projections to primary somatosensory cortex in rats extend long horizontal axons in layer I , 1998, The Journal of comparative neurology.

[26]  R Kötter,et al.  Morphology, electrophysiology and functional input connectivity of pyramidal neurons characterizes a genuine layer va in the primary somatosensory cortex. , 2006, Cerebral cortex.

[27]  D. Lo,et al.  Truncated and full-length TrkB receptors regulate distinct modes of dendritic growth , 2000, Nature Neuroscience.

[28]  Benjamin F. Grewe,et al.  Editorial overview: Cellular neuroscience , 2022, Current Opinion in Neurobiology.

[29]  H. Adesnik,et al.  Input normalization by global feedforward inhibition expands cortical dynamic range , 2009, Nature Neuroscience.

[30]  B. Connors,et al.  Intrinsic firing patterns of diverse neocortical neurons , 1990, Trends in Neurosciences.

[31]  J. Corbin,et al.  Programmed Cell Death Is Impaired in the Developing Brain of Fmr1 Mutants , 2013, Developmental Neuroscience.

[32]  J. Dobbing,et al.  Comparative aspects of the brain growth spurt. , 1979, Early human development.

[33]  Ian R. Wickersham,et al.  Convergent cortical innervation of striatal projection neurons , 2013, Nature Neuroscience.

[34]  Antonio Núñez Rodríguez.  Recuerdos de mi vida , 2014 .

[35]  S. Nelson,et al.  Intact Long-Term Potentiation but Reduced Connectivity between Neocortical Layer 5 Pyramidal Neurons in a Mouse Model of Rett Syndrome , 2009, The Journal of Neuroscience.

[36]  R. Kötter,et al.  Layer-Specific Intracolumnar and Transcolumnar Functional Connectivity of Layer V Pyramidal Cells in Rat Barrel Cortex , 2001, The Journal of Neuroscience.

[37]  Dong-Ming Yu,et al.  Prenatal alcohol exposure induces long-term changes in dendritic spines and synapses in the mouse visual cortex. , 2010, Alcohol and alcoholism.

[38]  Alex M. Thomson,et al.  Neocortical Layer 6, A Review , 2010, Front. Neuroanat..

[39]  M. Miller,et al.  Limited ethanol exposure selectively alters the proliferation of precursor cells in the cerebral cortex. , 1996, Alcoholism, clinical and experimental research.

[40]  Roberto Araya,et al.  Dendritic spines linearize the summation of excitatory potentials , 2006, Proceedings of the National Academy of Sciences.

[41]  K Genz,et al.  Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. , 2000, Science.

[42]  Huibert D. Mansvelder,et al.  Increased Threshold for Spike-Timing-Dependent Plasticity Is Caused by Unreliable Calcium Signaling in Mice Lacking Fragile X Gene Fmr1 , 2007, Neuron.

[43]  C. Blakemore,et al.  Pyramidal neurons in layer 5 of the rat visual cortex. I. Correlation among cell morphology, intrinsic electrophysiological properties, and axon targets , 1994, The Journal of comparative neurology.

[44]  C. Blakemore,et al.  Pyramidal neurons in layer 5 of the rat visual cortex. II. Development of electrophysiological properties , 1994, The Journal of comparative neurology.

[45]  L. Becker,et al.  Dendritic atrophy in children with Down's syndrome , 1986, Annals of neurology.

[46]  Thomas K. Berger,et al.  Heterogeneity in the pyramidal network of the medial prefrontal cortex , 2006, Nature Neuroscience.

[47]  C. Valenzuela,et al.  Does moderate drinking harm the fetal brain? Insights from animal models , 2012, Trends in Neurosciences.

[48]  S. Giannetti,et al.  Overexpression of the p75 neurotrophin receptor in the sensori-motor cortex of rats exposed to ethanol during early postnatal life , 2003, Neuroscience Letters.

[49]  J. Lübke,et al.  Excitatory signal flow and connectivity in a cortical column: focus on barrel cortex , 2007, Brain Structure and Function.

[50]  E. Callaway,et al.  Excitatory cortical neurons form fine-scale functional networks , 2005, Nature.

[51]  K. Sakai,et al.  Reinforcement learning: computing the temporal difference of values via distinct corticostriatal pathways , 2012, Trends in Neurosciences.

[52]  B. Antalffy,et al.  Decreased Dendritic Branching in Frontal, Motor and Limbic Cortex in Rett Syndrome Compared with Trisomy 21 , 1998, Journal of neuropathology and experimental neurology.

[53]  Ashok Kumar,et al.  Increased pro-nerve growth factor and p75 neurotrophin receptor levels in developing hypothyroid rat cerebral cortex are associated with enhanced apoptosis. , 2006, Endocrinology.

[54]  M. Larkum,et al.  Signaling of Layer 1 and Whisker-Evoked Ca2+ and Na+ Action Potentials in Distal and Terminal Dendrites of Rat Neocortical Pyramidal Neurons In Vitro and In Vivo , 2002, The Journal of Neuroscience.

[55]  H. Moser,et al.  Dendritic anomalies in disorders associated with mental retardation. , 1999, Cerebral cortex.

[56]  S. Giannetti,et al.  Organization of cortico-cortical associative projections in rats exposed to ethanol during early postnatal life , 2003, Brain Research Bulletin.

[57]  A. Polsky,et al.  Properties of basal dendrites of layer 5 pyramidal neurons: a direct patch-clamp recording study , 2007, Nature Neuroscience.

[58]  T. Lindsley,et al.  Ethanol alters BDNF-induced Rho GTPase activation in axonal growth cones. , 2011, Alcoholism, clinical and experimental research.

[59]  David Sliepherdson.  Effects of Environmental Enrichment , 1994 .

[60]  Masanori Murayama,et al.  Inhibitory Regulation of Dendritic Activity in vivo , 2012, Front. Neural Circuits.

[61]  M. Larkum,et al.  Properties of Layer 6 Pyramidal Neuron Apical Dendrites , 2010, The Journal of Neuroscience.

[62]  J. Gibson,et al.  Postsynaptic FMRP Promotes the Pruning of Cell-to-Cell Connections among Pyramidal Neurons in the L5A Neocortical Network , 2014, The Journal of Neuroscience.

[63]  Matthew E. Larkum,et al.  Early Exposure to Alcohol Leads to Permanent Impairment of Dendritic Excitability in Neocortical Pyramidal Neurons , 2012, The Journal of Neuroscience.

[64]  M. London,et al.  Dendritic computation. , 2005, Annual review of neuroscience.

[65]  A. Colino,et al.  Role of low-voltage-activated calcium current on the firing pattern alterations induced by hypothyroidism in the rat hippocampus , 2010, Neuroscience.