Optogenetic activation of septal GABAergic afferents entrains neuronal firing in the medial habenula

Kyuhyun Choi; Youngin Lee; Changwoo Lee; Seokheon Hong; Soonje Lee; Shin Jung Kang; Ki Soon Shin

doi:10.1038/srep34800

Optogenetic activation of septal GABAergic afferents entrains neuronal firing in the medial habenula

Kyuhyun Choi, Youngin Lee, Changwoo Lee, Seokheon Hong, Soonje Lee, Shin Jung Kang, Ki Soon Shin

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15 Citations (Scopus)

Abstract

The medial habenula (MHb) plays an important role in nicotine-related behaviors such as nicotine aversion and withdrawal. The MHb receives GABAergic input from the medial septum/diagonal band of Broca (MS/DB), yet the synaptic mechanism that regulates MHb activity is unclear. GABA (3-aminobutyric acid) is a major inhibitory neurotransmitter activating both GABA_A receptors and GABA_B receptors. Depending on intracellular chloride concentration, however, GABA_A receptors also function in an excitatory manner. In the absence of various synaptic inputs, we found that MHb neurons displayed spontaneous tonic firing at a rate of about ∼4.4 Hz. Optogenetic stimulation of MS/DB inputs to the MHb evoked GABA_A receptor-mediated synaptic currents, which produced stimulus-locked neuronal firing. Subsequent delayed yet lasting_Activation of GABA_B receptors_Attenuated the intrinsic tonic firing. Consequently, septal GABAergic input_Alone orchestrates_Both excitatory GABA_A_And inhibitory GABA_B receptors, thereby entraining the firing of MHb neurons.

Original language	English
Article number	34800
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep34800
Publication status	Published - 5 Oct 2016

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title = "Optogenetic activation of septal GABAergic afferents entrains neuronal firing in the medial habenula",

abstract = "The medial habenula (MHb) plays an important role in nicotine-related behaviors such as nicotine aversion and withdrawal. The MHb receives GABAergic input from the medial septum/diagonal band of Broca (MS/DB), yet the synaptic mechanism that regulates MHb activity is unclear. GABA (3-aminobutyric acid) is a major inhibitory neurotransmitter activating both GABAA receptors and GABAB receptors. Depending on intracellular chloride concentration, however, GABAA receptors also function in an excitatory manner. In the absence of various synaptic inputs, we found that MHb neurons displayed spontaneous tonic firing at a rate of about ∼4.4 Hz. Optogenetic stimulation of MS/DB inputs to the MHb evoked GABAA receptor-mediated synaptic currents, which produced stimulus-locked neuronal firing. Subsequent delayed yet lastingActivation of GABAB receptorsAttenuated the intrinsic tonic firing. Consequently, septal GABAergic inputAlone orchestratesBoth excitatory GABAAAnd inhibitory GABAB receptors, thereby entraining the firing of MHb neurons.",

author = "Kyuhyun Choi and Youngin Lee and Changwoo Lee and Seokheon Hong and Soonje Lee and Kang, {Shin Jung} and Shin, {Ki Soon}",

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T1 - Optogenetic activation of septal GABAergic afferents entrains neuronal firing in the medial habenula

AU - Choi, Kyuhyun

AU - Lee, Youngin

AU - Lee, Changwoo

AU - Hong, Seokheon

AU - Lee, Soonje

AU - Kang, Shin Jung

AU - Shin, Ki Soon

PY - 2016/10/5

Y1 - 2016/10/5

N2 - The medial habenula (MHb) plays an important role in nicotine-related behaviors such as nicotine aversion and withdrawal. The MHb receives GABAergic input from the medial septum/diagonal band of Broca (MS/DB), yet the synaptic mechanism that regulates MHb activity is unclear. GABA (3-aminobutyric acid) is a major inhibitory neurotransmitter activating both GABAA receptors and GABAB receptors. Depending on intracellular chloride concentration, however, GABAA receptors also function in an excitatory manner. In the absence of various synaptic inputs, we found that MHb neurons displayed spontaneous tonic firing at a rate of about ∼4.4 Hz. Optogenetic stimulation of MS/DB inputs to the MHb evoked GABAA receptor-mediated synaptic currents, which produced stimulus-locked neuronal firing. Subsequent delayed yet lastingActivation of GABAB receptorsAttenuated the intrinsic tonic firing. Consequently, septal GABAergic inputAlone orchestratesBoth excitatory GABAAAnd inhibitory GABAB receptors, thereby entraining the firing of MHb neurons.

AB - The medial habenula (MHb) plays an important role in nicotine-related behaviors such as nicotine aversion and withdrawal. The MHb receives GABAergic input from the medial septum/diagonal band of Broca (MS/DB), yet the synaptic mechanism that regulates MHb activity is unclear. GABA (3-aminobutyric acid) is a major inhibitory neurotransmitter activating both GABAA receptors and GABAB receptors. Depending on intracellular chloride concentration, however, GABAA receptors also function in an excitatory manner. In the absence of various synaptic inputs, we found that MHb neurons displayed spontaneous tonic firing at a rate of about ∼4.4 Hz. Optogenetic stimulation of MS/DB inputs to the MHb evoked GABAA receptor-mediated synaptic currents, which produced stimulus-locked neuronal firing. Subsequent delayed yet lastingActivation of GABAB receptorsAttenuated the intrinsic tonic firing. Consequently, septal GABAergic inputAlone orchestratesBoth excitatory GABAAAnd inhibitory GABAB receptors, thereby entraining the firing of MHb neurons.

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ER -

Optogenetic activation of septal GABAergic afferents entrains neuronal firing in the medial habenula

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