The Role of Serotonin in Early Cortical Development

The cerebral cortex is widely innervated by serotonin (5-HT)-containing axons originating from neurons in the raphe nuclei. The early development of this monoamine system in the cortex prompted speculation long ago that it has important functions in cortical maturation and plasticity. Here we review evidence, derived from a plethora of studies and from our recent unpublished work, that supports an important role for 5-HT in a number of major events in the developing cortex, especially at the early stages. This evidence points to a regulatory role for 5-HT in neuronal proliferation, migration and differentiation, and in preventing apoptotic cell death.

[1]  A. Kriegstein,et al.  Cell Coupling and Uncoupling in the Ventricular Zone of Developing Neocortex , 1997, The Journal of Neuroscience.

[2]  P. Gaspar,et al.  Transient Uptake and Storage of Serotonin in Developing Thalamic Neurons , 1996, Neuron.

[3]  M. Marín‐Padilla,et al.  Neocortical Development , 1992, Journal of Cognitive Neuroscience.

[4]  P. Gaspar,et al.  Plasma Membrane Transporters of Serotonin, Dopamine, and Norepinephrine Mediate Serotonin Accumulation in Atypical Locations in the Developing Brain of Monoamine Oxidase A Knock-Outs , 1998, The Journal of Neuroscience.

[5]  S. Heinemann,et al.  Embryonic Expression of the 5-HT3 Receptor Subunit, 5-HT3R-A, in the Rat: An in Situ Hybridization Study , 1995, Molecular and Cellular Neuroscience.

[6]  K. Roth,et al.  Apoptosis and brain development. , 2001, Mental retardation and developmental disabilities research reviews.

[7]  J H Haring,et al.  Dentate granule cell function after neonatal treatment with parachloroamphetamine or 5,7-dihydroxytryptamine. , 1999, Brain research. Developmental brain research.

[8]  Q. Gu,et al.  Neuromodulatory transmitter systems in the cortex and their role in cortical plasticity , 2002, Neuroscience.

[9]  A. Lavdas,et al.  Serotonin Promotes the Differentiation of Glutamate Neurons in Organotypic Slice Cultures of the Developing Cerebral Cortex , 1997, The Journal of Neuroscience.

[10]  Christine F. Hohmann,et al.  Behavioral consequences of abnormal cortical development: insights into developmental disabilities , 1997, Behavioural Brain Research.

[11]  F. Bloom,et al.  The 5-HT3 Receptor Is Present in Different Subpopulations of GABAergic Neurons in the Rat Telencephalon , 1997, The Journal of Neuroscience.

[12]  J. Haring,et al.  Serotonin regulates synaptic connections in the dentate molecular layer of adult rats via 5-HT1a receptors: evidence for a glial mechanism , 1998, Brain Research.

[13]  P. Levitt,et al.  Identification of a sensitive period of prenatal cocaine exposure that alters the development of the anterior cingulate cortex. , 2001, Cerebral cortex.

[14]  P. Gaspar,et al.  Effects of monoamine oxidase A inhibition on barrel formation in the mouse somatosensory cortex: Determination of a sensitive developmental period , 1998, The Journal of comparative neurology.

[15]  A. Daszuta,et al.  Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats , 1999, Neuroscience.

[16]  John G. Parnavelas,et al.  The origin and migration of cortical neurones: new vistas , 2000, Trends in Neurosciences.

[17]  J. Lauder,et al.  Serotonin as a regulator of craniofacial morphogenesis: site specific malformations following exposure to serotonin uptake inhibitors. , 1992, Teratology.

[18]  Patricia Gaspar,et al.  Lack of Barrels in the Somatosensory Cortex of Monoamine Oxidase A–Deficient Mice: Role of a Serotonin Excess during the Critical Period , 1996, Neuron.

[19]  M. Hamon,et al.  Neuronal localization of 5-HT1A receptor mRNA and protein in rat embryonic brain stem cultures. , 1994, Brain research. Developmental brain research.

[20]  H. Kennedy,et al.  The Nature and Nurture of Cortical Development , 1997 .

[21]  J. Parnavelas,et al.  Serotonin Promotes the Survival of Cortical Glutamatergic Neuronsin Vitro , 1997, Experimental Neurology.

[22]  Marla B Feller,et al.  Neurotransmitters and gap junctions in developing neural circuits , 2000, Brain Research Reviews.

[23]  G. Marsicano,et al.  Coexpression of the cannabinoid receptor type 1 with dopamine and serotonin receptors in distinct neuronal subpopulations of the adult mouse forebrain , 2002, Neuroscience.

[24]  M. Hamon,et al.  Native and Cloned 5-HT3A(S) Receptors Are Anchored to F-Actin in Clonal Cells and Neurons , 2002, Molecular and Cellular Neuroscience.

[25]  A. L. Holden,et al.  THE CENTRAL VISUAL PATHWAYS , 1977 .

[26]  O. Marín,et al.  A long, remarkable journey: Tangential migration in the telencephalon , 2001, Nature Reviews Neuroscience.

[27]  P. Rakić,et al.  Neurotransmitter receptors in the proliferative zones of the developing primate occipital lobe , 1995, The Journal of comparative neurology.

[28]  P. Fan.  Cannabinoid agonists inhibit the activation of 5-HT3 receptors in rat nodose ganglion neurons. , 1995, Journal of neurophysiology.

[29]  P. Gaspar,et al.  Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. , 1995, Science.

[30]  R. Silver,et al.  Mast cells in the brain: evidence and functional significance , 1996, Trends in Neurosciences.

[31]  E. Azmitia,et al.  5-HT1A agonist and dexamethasone reversal of para-chloroamphetamine induced loss of MAP-2 and synaptophysin immunoreactivity in adult rat brain , 1995, Brain Research.

[32]  H. Siegel,et al.  5. Aggressive Behavior , 2014 .

[33]  J. Krieglstein,et al.  Neuroprotective effect of 5-HT1A receptor agonist, Bay X 3702, demonstrated in vitro and in vivo. , 1998, European journal of pharmacology.

[34]  J. Lauder,et al.  Serotonin as a differentiation signal in early neurogenesis. , 1978, Developmental neuroscience.

[35]  J. Lauder,et al.  Development of the serotonergic system in the rat embryo: An immunocytochemical study , 1983, Brain Research Bulletin.

[36]  B. Jankovič,et al.  Neuroimmunomodulation: facts and dilemmas. , 1989, Immunology letters.

[37]  M. Martres,et al.  Induction of serotonin transporter by hypoxia in pulmonary vascular smooth muscle cells. Relationship with the mitogenic action of serotonin. , 1999, Circulation research.

[38]  A. Galaburda,et al.  Normal and Abnormal Development of the Cortex , 1997, Research and Perspectives in Neurosciences.

[39]  J. Lauder,et al.  Serotonin uptake in the ectoplacental cone and placenta of the mouse. , 1993, Placenta.

[40]  J. Bockaert,et al.  Activation of 5-HT1A receptors expressed in NIH-3T3 cells induces focus formation and potentiates EGF effect on DNA synthesis. , 1992, Molecular biology of the cell.

[41]  J. Harvey,et al.  New evidence for neurotransmitter influences on brain development , 1997, Trends in Neurosciences.

[42]  R. Silver,et al.  Mast Cells Migrate from Blood to Brain , 2000, The Journal of Neuroscience.

[43]  B. Ahlemeyer,et al.  S-100β protects cultured neurons against glutamate- and staurosporine-induced damage and is involved in the antiapoptotic action of the 5 HT1A-receptor agonist, Bay x 3702 , 2000, Brain Research.

[44]  E. Azmitia,et al.  Colchicine-induced cytoskeletal collapse and apoptosis in N-18 neuroblastoma cultures is rapidly reversed by applied S-100β , 2001, Brain Research.

[45]  J. Lauder,et al.  Neurotransmitters as morphogens. , 1988, Progress in brain research.

[46]  Elizabeth Gould,et al.  Serotonin and Hippocampal Neurogenesis , 1999, Neuropsychopharmacology.

[47]  M. Burkhardt,et al.  5‐HydroxytryptamineiA Agonists A New Therapeutic Principle for Stroke Treatment , 1990, Stroke.

[48]  S. M. Williams,et al.  Central Visual Pathways , 2001 .

[49]  Patricia M. Whitaker-Azmitia,et al.  Serotonin and brain development: role in human developmental diseases , 2001, Brain Research Bulletin.

[50]  J. Olney,et al.  Apoptosis in the in Vivo Mammalian Forebrain , 2001, Neurobiology of Disease.

[51]  Patricia Gaspar,et al.  Interactions between TrkB Signaling and Serotonin Excess in the Developing Murine Somatosensory Cortex: A Role in Tangential and Radial Organization of Thalamocortical Axons , 2002, The Journal of Neuroscience.

[52]  E. Azmitia.  Cajal's hypotheses on neurobiones and neurotropic factor match properties of microtubules and S-100 beta. , 2002, Progress in brain research.

[53]  L. Descarries,et al.  Similar ultrastructural distribution of the 5-HT2A serotonin receptor and microtubule-associated protein MAP1A in cortical dendrites of adult rat , 2002, Neuroscience.

[54]  J. Lauder,et al.  Neurotransmitters as growth regulatory signals: role of receptors and second messengers , 1993, Trends in Neurosciences.

[55]  P. Gaspar,et al.  Developmental expression of monoamine oxidases A and B in the central and peripheral nervous systems of the mouse , 2002, The Journal of comparative neurology.

[56]  M. Barbacid,et al.  TrkB Signaling Is Required for Postnatal Survival of CNS Neurons and Protects Hippocampal and Motor Neurons from Axotomy-Induced Cell Death , 1997, The Journal of Neuroscience.

[57]  R. Pakala,et al.  Mitogenic effect of serotonin on vascular endothelial cells. , 1994, Circulation.

[58]  M. Jacobson,et al.  Embryonic vertebrate central nervous system: Revised terminology , 1970 .

[59]  P P Humphrey,et al.  International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). , 1994, Pharmacological reviews.

[60]  E. Azmitia,et al.  Prenatal cocaine delays astroglial maturation: immunodensitometry shows increased markers of immaturity (vimentin and GAP-43) and decreased proliferation and production of the growth factor S-100. , 1996, Brain research. Developmental brain research.

[61]  Khan,et al.  Role of serotonin in fish immunomodulation , 1997, The Journal of experimental biology.

[62]  É. Mezey,et al.  Expression of the CB1 and CB2 receptor messenger RNAs during embryonic development in the rat , 1997, Neuroscience.

[63]  J. Launay,et al.  5-HT2B receptor-mediated serotonin morphogenetic functions in mouse cranial neural crest and myocardiac cells. , 1997, Development.

[64]  H. Supèr,et al.  The functions of the preplate in development and evolution of the neocortex and hippocampus , 1998, Brain Research Reviews.

[65]  Tobey M. Tam,et al.  Serotonin Promotes Go-Dependent Neuronal Migration in Caenorhabditis elegans , 2002, Current Biology.

[66]  H. Loos,et al.  Monoaminergic afferents to cortex modulate structural plasticity in the barrelfield of the mouse. , 1994, Brain research. Developmental brain research.

[67]  D. Price,et al.  Radial migration in the cerebral cortex is enhanced by signals from thalamus , 2001, European Journal of Neuroscience.

[68]  N. Gilula,et al.  Gap junctional communication and development , 1989, Trends in Neurosciences.

[69]  R. Silver,et al.  Brain mast cell degranulation regulates blood-brain barrier. , 1996, Journal of neurobiology.