Activation of 5‐<scp>HT</scp> receptors inhibits <scp>GABA</scp>ergic transmission by pre‐and post‐synaptic mechanisms in layer <scp>II/III</scp> of the juvenile rat auditory cortex

García-Oscos, Francisco; Torres-Ramirez, Oswaldo; Dinh, Lu; Galindo-Charles, Luis; Padilla, Elsy Arlene Pérez; Pineda, Juan Carlos; Atzori, Marco; Salgado, Humberto

doi:10.1002/syn.21794

Cited by 14 publications

(6 citation statements)

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“…Serotonin receptor 2A (5-HT 2A ) belongs to the G-protein-coupled receptor (GPCR) family and is broadly distributed within the brain, showing high expression in the olfactory tubercle, cortical areas, and dentate gyrus [ 13 , 14 ]. Functionally, 5-HT 2A is involved in neurogenesis and can modulate synaptic plasticity via long-lasting increases in the excitability and firing rate of glutamatergic and GABAergic neurons [ 15 , 16 ]. The 5-HT 2A receptor is implicated in numerous CNS disorders, including bipolar disorder, depression, and schizophrenia [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Serotonin Receptor 5-HT2A Regulates TrkB Receptor Function in Heteroreceptor Complexes

Ilchibaeva

Цыбко

Zeug

et al. 2022

Cells

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Serotonin receptor 5-HT2A and tropomyosin receptor kinase B (TrkB) strongly contribute to neuroplasticity regulation and are implicated in numerous neuronal disorders. Here, we demonstrate a physical interaction between 5-HT2A and TrkB in vitro and in vivo using co-immunoprecipitation and biophysical and biochemical approaches. Heterodimerization decreased TrkB autophosphorylation, preventing its activation with agonist 7,8-DHF, even with low 5-HT2A receptor expression. A blockade of 5-HT2A receptor with the preferential antagonist ketanserin prevented the receptor-mediated downregulation of TrkB phosphorylation without restoring the TrkB response to its agonist 7,8-DHF in vitro. In adult mice, intraperitoneal ketanserin injection increased basal TrkB phosphorylation in the frontal cortex and hippocampus, which is in accordance with our findings demonstrating the prevalence of 5-HT2A–TrkB heteroreceptor complexes in these brain regions. An expression analysis revealed strong developmental regulation of 5-HT2A and TrkB expressions in the cortex, hippocampus, and especially the striatum, demonstrating that the balance between TrkB and 5-HT2A may shift in certain brain regions during postnatal development. Our data reveal the functional role of 5-HT2A–TrkB receptor heterodimerization and suggest that the regulated expression of 5-HT2A and TrkB is a molecular mechanism for the brain-region-specific modulation of TrkB functions during development and under pathophysiological conditions.

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Section: Introductionmentioning

confidence: 99%

Serotonin Receptor 5-HT2A Regulates TrkB Receptor Function in Heteroreceptor Complexes

Ilchibaeva

Цыбко

Zeug

et al. 2022

Cells

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“…Animal studies have shown that 5-HT decreases GABAergic neurotransmission pre-and postsynaptically in the primary auditory cortex via 5-HT 1A and 5-HT 2A receptors, respectively, and decreases firing rate, input resistance and firing rate adaptation of pyramidal cells in juvenile rats. 13,14 Although SSRI treatment has been associated with plasticity in the primary visual cortex, 15 this association has not been observed in the primary auditory cortex. 16 Tryptophan depletion studies in humans suggest that 5-HT affects early, attention-related processing of auditory stimulus information.…”

Section: Introductionmentioning

confidence: 99%

5-HT_1A receptor, 5-HT_2A receptor and serotonin transporter binding in the human auditory cortex in depression

Steinberg¹,

Underwood

Bakalian

et al. 2019

jpn

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“…2004; De Almeida & Mengod, 2007; García‐Oscos et al . 2015), often with opposite effects on neuronal activity depending on the type of receptor activated. In addition, different neuromodulatory systems interact with each other (Esteban et al .…”

Section: Discussionmentioning

confidence: 99%

“…In normal physiological situations, neuromodulatory systems can exert a global impact on the excitatory and inhibitory network at a time scale of minutes. Neuromodulators target both pyramidal cells and inhibitory interneurons (acetylcholine: Metherate et al 1992;Alitto & Dan, 2012;noradrenaline: Toussay et al 2013;Salgado et al 2016;serotonin: Aznar et al 2003;Santana et al 2004;De Almeida & Mengod, 2007;García-Oscos et al 2015), often with opposite effects on neuronal activity depending on the type of receptor activated. In addition, different neuromodulatory systems interact with each other (Esteban et al 1996;Villégier et al 2003) leading to difficulties in predicting the net effect of a particular neuromodulator action on cortical activity (reviewed by Edeline, 2012).…”

Section: Physiological Control Of Cortical Inhibitionsmentioning

confidence: 99%

Increasing excitation versus decreasing inhibition in auditory cortex: consequences on the discrimination performance between communication sounds

Gaucher

Yger

Edeline

2020

The Journal of Physiology

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Key points Enhancing cortical excitability can be achieved by either reducing intracortical inhibition or by enhancing intracortical excitation. Here we compare the consequences of reducing intracortical inhibition and of enhancing intracortical excitation on the processing of communication sounds in the primary auditory cortex. Local application of gabazine and of AMPA enlarged the spectrotemporal receptive fields and increased the responses to communication to the same extent. The Mutual Information (an index of the cortical neurons’ ability to discriminate between natural sounds) was increased in both cases, as were the noise and signal correlations. Spike‐timing reliability was only increased after gabazine application and post‐excitation suppression was affected in the opposite way: it was increased when reducing the intracortical inhibition but was eliminated by enhancing the excitation. A computational model suggests that these results can be explained by an additive effect vs. a multiplicative effect Abstract The level of excitability of cortical circuits is often viewed as one of the critical factors controlling perceptive performance. In theory, enhancing cortical excitability can be achieved either by reducing inhibitory currents or by increasing excitatory currents. Here, we evaluated whether reducing inhibitory currents or increasing excitatory currents in auditory cortex similarly affects the neurons’ ability to discriminate between communication sounds. We attenuated the inhibitory currents by application of gabazine (GBZ), and increased the excitatory currents by applying AMPA in the auditory cortex while testing frequency receptive fields and responses to communication sounds. GBZ and AMPA enlarged the receptive fields and increased the responses to communication sounds to the same extent. The spike‐timing reliability of neuronal responses was largely increased when attenuating the intracortical inhibition but not after increasing the excitation. The discriminative abilities of cortical cells increased in both cases but this increase was more pronounced after attenuating the inhibition. The shape of the response to communication sounds was modified in the opposite direction: reducing inhibition increased post‐excitation suppression whereas this suppression tended to disappear when increasing the excitation. A computational model indicates that the additive effect promoted by AMPA vs. the multiplicative effect of GBZ on neuronal responses, together with the dynamics of spontaneous cortical activity, can explain these differences. Thus, although apparently equivalent for increasing cortical excitability, acting on inhibition vs. on excitation impacts differently the cortical ability to discriminate natural stimuli, and only modulating inhibition changed efficiently the cortical representation of communication sounds.

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Activation of 5‐HT receptors inhibits GABAergic transmission by pre‐and post‐synaptic mechanisms in layer II/III of the juvenile rat auditory cortex

Cited by 14 publications

References 53 publications

Serotonin Receptor 5-HT2A Regulates TrkB Receptor Function in Heteroreceptor Complexes

Serotonin Receptor 5-HT2A Regulates TrkB Receptor Function in Heteroreceptor Complexes

5-HT_1A receptor, 5-HT_2A receptor and serotonin transporter binding in the human auditory cortex in depression

Increasing excitation versus decreasing inhibition in auditory cortex: consequences on the discrimination performance between communication sounds

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Activation of 5‐HT receptors inhibits GABAergic transmission by pre‐and post‐synaptic mechanisms in layer II/III of the juvenile rat auditory cortex

Cited by 14 publications

References 53 publications

Serotonin Receptor 5-HT2A Regulates TrkB Receptor Function in Heteroreceptor Complexes

Serotonin Receptor 5-HT2A Regulates TrkB Receptor Function in Heteroreceptor Complexes

5-HT1A receptor, 5-HT2A receptor and serotonin transporter binding in the human auditory cortex in depression

Increasing excitation versus decreasing inhibition in auditory cortex: consequences on the discrimination performance between communication sounds

Contact Info

Product

Resources

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5-HT_1A receptor, 5-HT_2A receptor and serotonin transporter binding in the human auditory cortex in depression