Marco Capogna

Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission. / Sengupta, Ayesha; Bocchio, Marco; Bannerman, David M; Sharp, Trevor; Capogna, Marco.

In: The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 37, No. 7, 15.02.2017, p. 1785-1796.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Sengupta, A, Bocchio, M, Bannerman, DM, Sharp, T & Capogna, M 2017, 'Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission', The Journal of neuroscience : the official journal of the Society for Neuroscience, vol. 37, no. 7, pp. 1785-1796. https://doi.org/10.1523/JNEUROSCI.2238-16.2016

APA

Sengupta, A., Bocchio, M., Bannerman, D. M., Sharp, T., & Capogna, M. (2017). Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission. The Journal of neuroscience : the official journal of the Society for Neuroscience, 37(7), 1785-1796. https://doi.org/10.1523/JNEUROSCI.2238-16.2016

CBE

Sengupta A, Bocchio M, Bannerman DM, Sharp T, Capogna M. 2017. Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission. The Journal of neuroscience : the official journal of the Society for Neuroscience. 37(7):1785-1796. https://doi.org/10.1523/JNEUROSCI.2238-16.2016

MLA

Sengupta, Ayesha et al. "Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission". The Journal of neuroscience : the official journal of the Society for Neuroscience. 2017, 37(7). 1785-1796. https://doi.org/10.1523/JNEUROSCI.2238-16.2016

Vancouver

Sengupta A, Bocchio M, Bannerman DM, Sharp T, Capogna M. Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2017 Feb 15;37(7):1785-1796. https://doi.org/10.1523/JNEUROSCI.2238-16.2016

Author

Sengupta, Ayesha ; Bocchio, Marco ; Bannerman, David M ; Sharp, Trevor ; Capogna, Marco. / Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission. In: The Journal of neuroscience : the official journal of the Society for Neuroscience. 2017 ; Vol. 37, No. 7. pp. 1785-1796.

Bibtex

@article{e2be5c9be8974177bc5f1fee060ad376,
title = "Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission",
abstract = "The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10-20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT2A and 5-HT1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output.SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders. Therefore, it is essential to determine the physiological mechanisms through which 5-HT neurons in the dorsal raphe nuclei modulate amygdala circuits. Here, we combined optogenetic, electrophysiological, and pharmacological approaches to study the effects of activation of 5-HT axons in the basal nucleus of the amygdala (BA). We found that 5-HT neurons co-release 5-HT and glutamate onto BA neurons in a cell-type-specific and frequency-dependent manner. Therefore, we suggest that theories on the contribution of 5-HT neurons to amygdala function should be revised to incorporate the concept of 5-HT/glutamate cotransmission.",
keywords = "Amygdala, Animals, Animals, Newborn, Channelrhodopsins, Excitatory Amino Acid Agents, Female, GABA Antagonists, Glutamic Acid, Luminescent Proteins, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net, Neurons, Piperazines, Pyridines, Receptors, Serotonin, Serotonin, Serotonin Antagonists, Serotonin Plasma Membrane Transport Proteins, Synaptic Transmission, Journal Article",
author = "Ayesha Sengupta and Marco Bocchio and Bannerman, {David M} and Trevor Sharp and Marco Capogna",
note = "Copyright {\textcopyright} 2017 Sengupta et al.",
year = "2017",
month = feb,
day = "15",
doi = "10.1523/JNEUROSCI.2238-16.2016",
language = "English",
volume = "37",
pages = "1785--1796",
journal = "The Journal of neuroscience : the official journal of the Society for Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "7",

}

RIS

TY - JOUR

T1 - Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission

AU - Sengupta, Ayesha

AU - Bocchio, Marco

AU - Bannerman, David M

AU - Sharp, Trevor

AU - Capogna, Marco

N1 - Copyright © 2017 Sengupta et al.

PY - 2017/2/15

Y1 - 2017/2/15

N2 - The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10-20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT2A and 5-HT1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output.SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders. Therefore, it is essential to determine the physiological mechanisms through which 5-HT neurons in the dorsal raphe nuclei modulate amygdala circuits. Here, we combined optogenetic, electrophysiological, and pharmacological approaches to study the effects of activation of 5-HT axons in the basal nucleus of the amygdala (BA). We found that 5-HT neurons co-release 5-HT and glutamate onto BA neurons in a cell-type-specific and frequency-dependent manner. Therefore, we suggest that theories on the contribution of 5-HT neurons to amygdala function should be revised to incorporate the concept of 5-HT/glutamate cotransmission.

AB - The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10-20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT2A and 5-HT1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output.SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders. Therefore, it is essential to determine the physiological mechanisms through which 5-HT neurons in the dorsal raphe nuclei modulate amygdala circuits. Here, we combined optogenetic, electrophysiological, and pharmacological approaches to study the effects of activation of 5-HT axons in the basal nucleus of the amygdala (BA). We found that 5-HT neurons co-release 5-HT and glutamate onto BA neurons in a cell-type-specific and frequency-dependent manner. Therefore, we suggest that theories on the contribution of 5-HT neurons to amygdala function should be revised to incorporate the concept of 5-HT/glutamate cotransmission.

KW - Amygdala

KW - Animals

KW - Animals, Newborn

KW - Channelrhodopsins

KW - Excitatory Amino Acid Agents

KW - Female

KW - GABA Antagonists

KW - Glutamic Acid

KW - Luminescent Proteins

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Nerve Net

KW - Neurons

KW - Piperazines

KW - Pyridines

KW - Receptors, Serotonin

KW - Serotonin

KW - Serotonin Antagonists

KW - Serotonin Plasma Membrane Transport Proteins

KW - Synaptic Transmission

KW - Journal Article

U2 - 10.1523/JNEUROSCI.2238-16.2016

DO - 10.1523/JNEUROSCI.2238-16.2016

M3 - Journal article

C2 - 28087766

VL - 37

SP - 1785

EP - 1796

JO - The Journal of neuroscience : the official journal of the Society for Neuroscience

JF - The Journal of neuroscience : the official journal of the Society for Neuroscience

SN - 0270-6474

IS - 7

ER -