Subtype specific roles of serotonin receptors in the spine formation of cortical neurons in vitro

Yoshida, Hiroyuki; Kanamaru, Chisako; Ohtani, Akiko; Li, Fēi; Senzaki, Kouji; Shiga, Takashi

doi:10.1016/j.neures.2011.07.1824

Cited by 29 publications

(25 citation statements)

References 19 publications

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“…5HT2ARs influence low-frequency field potential oscillations in rat frontal cortex (Celada et al, 2008). Recently 5HT2ARs has been observed to spur spinogenesis (Yoshida et al, 2011). Taken together, the enhanced consolidation of fear memory observed in mice that received TCB-2 post-training treatment may be a reflection of 5HT2AR activation effects on local field potentials, enhanced hippocampal and amygdala neuronal activity and spinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice

et al. 2013

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Excessive fear is a hallmark of several emotional and mental disorders such as phobias and panic disorders. Considerable attention is focused on defining the neurobiological mechanisms of the extinction of conditioned fear memory in an effort to identify mechanisms that may hold clinical significance for remediating aberrant fear memory. Serotonin modulates the acquisition and retention of conditioned emotional memory, and the serotonin 2A receptor (5HT2AR) may be one of the postsynaptic targets mediating such effects. Here we tested the hypothesis that the 5HT2AR regulates the consolidation and extinction of fear memory in male C57BL/6J mice. The influence of 5HT2ARs on memory consolidation was further confirmed with a novel object recognition task. With a trace fear conditioning paradigm, administration of the 5HT2AR agonist TCB-2 (1.0 mg/kg, i.p.) before the extinction test facilitated the acquisition of extinction of fear memory as compared to vehicle treatment. In contrast, administration of the 5HT2AR antagonist MDL 11,939 (0.5 mg/kg, i.p.) delayed the acquisition of extinction of fear memory. Further, the post-conditioning administration of TCB-2 enhanced contextual and cued fear memory, possibly by facilitating the consolidation of fear memory. Administration of TCB-2 also facilitated the acquisition of extinction of fear memory in delay fear conditioned mice. Stimulation or blockade of 5HT2ARs did not affect the encoding or retrieval of conditioned fear memory. Finally, administration of TCB-2 right after training in an object recognition task enhanced the consolidation of object memory. These results suggest that stimulation of 5HT2ARs facilitates the consolidation and extinction of trace and delay cued fear memory and the consolidation of object memory. Blocking the 5HT2AR impairs the acquisition of fear memory extinction. The results support the view that serotonergic activation of the 5HT2AR provides an important modulatory influence on circuits engaged during extinction learning. Taken together these results suggest that the 5HT2AR may be a potential therapeutic target for enhancing hippocampal and amygdala-dependent memory.

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Section: Discussionmentioning

confidence: 99%

Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice

et al. 2013

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“…The 5‐HT2A receptors primarily express in the proximal dendrites and dendritic spines, while 5‐HT2C receptors are highly expressed in the distal dendrites and synaptic spines of cortical pyramidal neurons . Activation of 5‐HT2A/2C receptors by 2,5‐dimethoxy‐4‐iodoamphetamine (DOI) increases synaptic spines and puncta (Figure ) . 5‐HT2A/2C receptors increase NMDAR‐mediated currents by activating the ERK1/2 pathway via the β‐arrestin/Src/dynamin cascade (Figure ) .…”

Section: Antipsychotic Drug‐targeted Receptors Regulate Neurites In Smentioning

confidence: 99%

“…Activation of 5‐HT1A decreases NMDAR‐mediated currents in pyramidal neurons of the prefrontal cortex through reduction of ERK1/2 activity, which leads to a decrease in microtubule‐associated protein 2 phosphorylation (Figure ) . 5‐HT1A agonist, 8‐hydroxy‐2‐(DI‐n‐propylamino) tetralin (8‐OH‐DPAT), reduces the number of dendritic spines and puncta, but not filopodia in cultured cortical neurons at day 15 . Conversely, reduced 5‐HT1A receptor activities have been reported to increase neurite outgrowth in primary hippocampal neurons and cultured rat cortical neurons .…”

Section: Antipsychotic Drug‐targeted Receptors Regulate Neurites In Smentioning

confidence: 99%

Effects of antipsychotic drugs on neurites relevant to schizophrenia treatment

Huang

Song

2018

Medicinal Research Reviews

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Although antipsychotic drugs are mainly used for treating schizophrenia, they are widely used for treating various psychiatric diseases in adults, the elderly, adolescents and even children. Today, about 1.2% of the worldwide population suffers from psychosis and related disorders, which translates to about 7.5 million subjects potentially targeted by antipsychotic drugs. Neurites project from the cell body of neurons and connect neurons to each other to form neural networks. Deficits in neurite outgrowth and integrity are implicated in psychiatric diseases including schizophrenia. Neurite deficits contribute to altered brain development, neural networking and connectivity as well as symptoms including psychosis and altered cognitive function. This review revealed that (1) antipsychotic drugs could have profound effects on neurites, synaptic spines and synapse, by which they may influence and regulate neural networking and plasticity; (2) antipsychotic drugs target not only neurotransmitter receptors but also intracellular signaling molecules regulating the signaling pathways responsible for neurite outgrowth and maintenance; (3) high doses and chronic administration of antipsychotic drugs may cause some loss of neurites, synaptic spines, or synapsis in the cortical structures. In addition, confounding effects causing neurite deficits may include elevated inflammatory cytokines and antipsychotic drug-induced metabolic side effects in patients on chronic antipsychotic therapy. Unraveling how antipsychotic drugs affect neurites and neural connectivity is essential for improving therapeutic outcomes and preventing aversive effects for patients on antipsychotic drug treatment.

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“…5-HT2A receptor activation alters dendritic spine area via a kalirin-7 dependent pathway (Jones et al, 2009). Stimulation of 5-HT2A receptors also changes the density of specific subtypes of dendritic spines (Yoshida et al, 2011). Those studies suggest that 5-HT2A receptors play a role in the regulation of dendritic spine architecture and actin cytoskeleton.…”

Section: 0 Introductionmentioning

confidence: 99%

Receptor-stimulated transamidation induces activation of Rac1 and Cdc42 and the regulation of dendritic spines

Kapadia

et al. 2017

Neuropharmacology

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Regulation of dendritic spines is an important component of synaptic function and plasticity whereas dendritic spine dysregulation is related to several psychiatric and neurological diseases. In the present study, we tested the hypothesis that serotonin (5-HT)2A/2C receptor-induced Rho family transamidation and activation regulates dendritic spine morphology and that activation of multiple types of receptors can induce transglutaminase(TGase)-catalyzed transamidation of small G proteins. We previously reported a novel 5-HT2A receptor downstream effector, TGase-catalyzed serotonylation of the small G protein Rac1 in A1A1v cells, a rat embryonic cortical cell line. We now extend these findings to rat primary cortical cultures which develop dendritic spines; stimulation of 5-HT2A/2C receptors increased transamidation of Rac1 and Cdc42, but not RhoA. Inhibition of TGases significantly decreased transamidation and activation of Rac1 and Cdc42, suggesting that transamidation led to their activation. In primary cortical cultures, stimulation of 5-HT2A/2C receptors by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane(DOI) caused a transient dendritic spine enlargement, which was blocked by TGase inhibition. Stimulation of both 5-HT2A and 5-HT2C receptors contributed to DOI-induced Rac1 transamidation in primary cortical cultures as demonstrated by selective antagonists. Furthermore, stimulation of muscarinic acetylcholine receptors and NMDA receptors also increased TGase-catalyzed Rac1 activation in SH-SY5Y cells and N2a cells, respectively. Receptor-stimulated TGase-catalyzed transamidation of Rac1 occurs at Q61, a site previously reported to be important in the inactivation of Rac1. These studies demonstrate that TGase-catalyzed transamidation and activation of small G proteins results from stimulation of multiple types of receptors and this novel signaling pathway can regulate dendritic spine morphology and plasticity.

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Subtype specific roles of serotonin receptors in the spine formation of cortical neurons in vitro

Cited by 29 publications

References 19 publications

Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice

Stimulation of serotonin 2A receptors facilitates consolidation and extinction of fear memory in C57BL/6J mice

Effects of antipsychotic drugs on neurites relevant to schizophrenia treatment

Receptor-stimulated transamidation induces activation of Rac1 and Cdc42 and the regulation of dendritic spines

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