Regulation of synapse density by 5-HT2A receptor agonist and antagonist in the spinal cord of chicken embryo

Niitsu, Yasushi; Hatnada, Shun; Hamaguchi, Kayoko; Murakami, Masahiko; Okado, Nobuo

doi:10.1016/0304-3940(95)11805-7

Cited by 41 publications

(21 citation statements)

References 8 publications

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“…At the cellular level, several previous in vitro and in vivo studies suggest that extracellular 5-HT levels may affect synaptic density or neurite branching and elongation in nonserotoninergic cortical neurons (Chubakov et al, 1986;Haydon et al, 1987;Okado et al, 1989, Sikich et al, 1990Okado et al, 1993;Chen et al, 1994;Niitsu et al, 1995;Yan et al, 1997). The results of our quantitative electron microscopic study provide no evidence of enhanced extracellular 5-HT exerting either a positive or a negative effect on synapse formation.…”

Section: Possible Mechanisms Of Serotonin-induced Alterations In 5-htcontrasting

confidence: 63%

Barrel Pattern Formation Requires Serotonin Uptake by Thalamocortical Afferents, and Not Vesicular Monoamine Release

et al. 2001

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Thalamocortical neurons innervating the barrel cortex in neonatal rodents transiently store serotonin (5-HT) in synaptic vesicles by expressing the plasma membrane serotonin transporter (5-HTT) and the vesicular monoamine transporter (VMAT2). 5-HTT knock-out (ko) mice reveal a nearly complete absence of 5-HT in the cerebral cortex by immunohistochemistry, and of barrels, both at P7 and adulthood. Quantitative electron microscopy reveals that 5-HTT ko affects neither the density of synapses nor the length of synaptic contacts in layer IV. VMAT2 ko mice, completely lacking activity-dependent vesicular release of monoamines including 5-HT, also show a complete lack of 5-HT in the cortex but display largely normal barrel fields, despite sometimes markedly reduced postnatal growth. Transient 5-HTT expression is thus required for barrel pattern formation, whereas activity-dependent vesicular 5-HT release is not.

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Section: Possible Mechanisms Of Serotonin-induced Alterations In 5-htcontrasting

confidence: 63%

Barrel Pattern Formation Requires Serotonin Uptake by Thalamocortical Afferents, and Not Vesicular Monoamine Release

et al. 2001

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“…There is some evidence suggesting that the 5-HT 2A receptor may play a role in regulating synapse number in embryonic chick spinal cord (17), but whether 5-HT exerts control over synaptic structural plasticity in mammalian cortical neurons through 5-HT 2A receptors is unknown.…”

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confidence: 99%

Rapid modulation of spine morphology by the 5-HT _2A serotonin receptor through kalirin-7 signaling

Jones¹,

Srivastava²,

Allen³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

182

168

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The 5-HT2A serotonin receptor is the most abundant serotonin receptor subtype in the cortex and is predominantly expressed in pyramidal neurons. The 5-HT 2A receptor is a target of several hallucinogens, antipsychotics, anxiolytics, and antidepressants, and it has been associated with several psychiatric disorders, conditions that are also associated with aberrations in dendritic spine morphogenesis. However, the role of 5-HT 2A receptors in regulating dendritic spine morphogenesis in cortical neurons is unknown. Here we show that the 5-HT 2A receptor is present in a subset of spines, in addition to dendritic shafts. It colocalizes with PSD-95 and with multiple PDZ protein-1 (MUPP1) in a subset of dendritic spines of rat cortical pyramidal neurons. MUPP1 is enriched in postsynaptic density (PSD) fractions, is targeted to spines in pyramidal neurons, and enhances the localization of 5-HT 2A receptors to the cell periphery. 5-HT2A receptor activation by the 5-HT 2 receptor agonist DOI induced a transient increase in dendritic spine size, as well as phosphorylation of p21-activated kinase (PAK) in cultured cortical neurons. PAK is a downstream target of the neuronal Rac guanine nucleotide exchange factor (RacGEF) kalirin-7 that is important for spine remodeling. Kalirin-7 regulates dendritic spine morphogenesis in neurons but its role in neuromodulator signaling has not been investigated. We show that peptide interference that prevents the localization of kalirin-7 to the postsynaptic density disrupts DOI-induced PAK phosphorylation and spine morphogenesis. These results suggest a potential role for serotonin signaling in modulating spine morphology and kalirin-7's function at cortical synapses.GPCR ͉ neuromodulator ͉ PAK ͉ Rac ͉ synapse D endritic spine morphogenesis is an important component of structural plasticity in the mammalian forebrain. Changes in dendritic spine shape, size, and number underlie synaptic functional changes and accompany neuronal development, learning and memory, and behavior (1). Additionally, abnormal spine morphogenesis has been associated with many neurodevelopmental, neuropsychiatric, and neurodegenerative diseases, suggesting the importance of appropriate development, plasticity, and maintenance of these structures to neuronal function (2). Spine morphogenesis relies on alterations in the actin cytoskeleton, but the molecular mechanisms that regulate this process are just beginning to be uncovered. The role of neuromodulators, in particular of serotonin, in spine remodeling is not well understood.The 5-HT 2A receptor is the most abundantly expressed serotonin receptor subtype in the cortex, and it is predominantly expressed in pyramidal neurons (3-5). It is a target of several hallucinogens, antipsychotics, anxiolytics, and antidepressants, and it has been functionally and genetically associated with schizophrenia, autism, attention-deficit/hyperactivity disorder, and affective disorders (6-11). 5-HT 2A receptors are expressed late in development, coinciding with the period of synapto...

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“…The serotonin 2 A (5-HT 2 A) receptor is known to be one of the major subtypes and is associated with psychological and mental events (Roth, 1994). The 5-HT 2 A receptor plays a role in facilitating the formation and maintenance of synapses (Niitsu et al, 1995). Staining for 5-HT 2 A shows the entire somata and dendritic tree of Purkinje cells in a rat cerebellum (Maeshima et al , 1998).…”

Section: Brain Stem and The Role Of Serotonin In Brain Development Anmentioning

confidence: 99%

“…In vitro studies have shown that that 5-HT inhibits the growth and arborization of Purkinje cell dendrites through 5-HT 2 A receptors and stimulates them through the 5-HT 1 A receptor (Kondoh et al, 2004). 5-HT promotes the formation of synapses in developing and mature brain and spinal cord (Chen et al, 1997;Niitsu et al, 1995;Okado et al, 1993), and this process is mediated by the 5-HT 2 A receptor in the spinal cord (Niitsu et al, 1995). Biochemical studies support the hypothesis that developmental defects of the raphe nuclei may make a major contribution to the structural and functional defects of cortical and subcortical structures.…”

Section: Brain Stem and The Role Of Serotonin In Brain Development Anmentioning

confidence: 99%

Characterization of the of the Pathological and Biochemical Markers That Correlate to the Clinical Features of Autism. Subproject 2. Contribution of Significant Delay of Neuronal Development and Metabolic Shift of Neurons to Clinical Phenotype of Autism

Węgiel¹,

Brown²

2013

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Regulation of synapse density by 5-HT2A receptor agonist and antagonist in the spinal cord of chicken embryo

Cited by 41 publications

References 8 publications

Barrel Pattern Formation Requires Serotonin Uptake by Thalamocortical Afferents, and Not Vesicular Monoamine Release

Barrel Pattern Formation Requires Serotonin Uptake by Thalamocortical Afferents, and Not Vesicular Monoamine Release

Rapid modulation of spine morphology by the 5-HT _2A serotonin receptor through kalirin-7 signaling

Characterization of the of the Pathological and Biochemical Markers That Correlate to the Clinical Features of Autism. Subproject 2. Contribution of Significant Delay of Neuronal Development and Metabolic Shift of Neurons to Clinical Phenotype of Autism

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Regulation of synapse density by 5-HT2A receptor agonist and antagonist in the spinal cord of chicken embryo

Cited by 41 publications

References 8 publications

Barrel Pattern Formation Requires Serotonin Uptake by Thalamocortical Afferents, and Not Vesicular Monoamine Release

Barrel Pattern Formation Requires Serotonin Uptake by Thalamocortical Afferents, and Not Vesicular Monoamine Release

Rapid modulation of spine morphology by the 5-HT 2A serotonin receptor through kalirin-7 signaling

Characterization of the of the Pathological and Biochemical Markers That Correlate to the Clinical Features of Autism. Subproject 2. Contribution of Significant Delay of Neuronal Development and Metabolic Shift of Neurons to Clinical Phenotype of Autism

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Rapid modulation of spine morphology by the 5-HT _2A serotonin receptor through kalirin-7 signaling