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Reference: Sengupta, A, Bocchio, M, Bannerman, DM et al., (2017). Control of amygdala circuits by 5-HT neurons via 5-HT and glutamate co-transmission. Journal of Neuroscience, 37 (7), 1785-1796.Citable link to this page:


Control of amygdala circuits by 5-HT neurons via 5-HT and glutamate co-transmission

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. Thus, 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 (ChR2) genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed this effect was mediated by glutamate and not 5-HT since it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10-20Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT since they were blocked by antagonists of 5-HT2A and 5-HT1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often co-existed 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 (PNs), 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. Hence, it is essential to dissect 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 (BA) of the amygdala. We found that 5-HT neurons co-release 5-HT and glutamate onto BA neurons in a cell type-specific and frequency-dependent manner. Thus, 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 co-transmission.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's versionNotes:Copyright © 2017 Sengupta et al.This is an open-access article distributed under the terms of the Creative Commons Attribution LicenseCreative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction inanymedium providedthatthe original work is properly attributed.

Bibliographic Details

Publisher: Society for Neuroscience

Publisher Website:

Journal: Journal of Neurosciencesee more from them

Publication Website:

Volume: 37

Issue: 7

Extent: 1785-1796

Issue Date: 13 January 2017



Eissn: 1529-2401

Issn: 0270-6474

Uuid: uuid:a1e58a9b-45dc-42ba-896a-397930b34ccf

Urn: uri:a1e58a9b-45dc-42ba-896a-397930b34ccf

Pubs-id: pubs:671547 Item Description

Type: journal-article;

Language: eng

Version: Publisher's versionKeywords: amygdala electrophysiology interneuron optogenetics serotonin synaptic transmission


Autor: Sengupta, A - Oxford, MSD, Pharmacology fundingWellcome–National Institutes of Health Studentship grantNumber100933-Z-13-Z - -



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