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

  • Ayesha Sengupta, Department of Pharmacology, University of Oxford, Oxford, OX1 3QT United Kingdom.
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  • Marco Bocchio, Medical Research Council Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford, OX1 3TH United Kingdom.
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  • David M Bannerman, University of Oxford, Department of Experimental Psychology, Tinbergen Building, Oxford, OX1 3UD, United Kingdom, +44 1865 271367.
  • ,
  • Trevor Sharp, Department of Pharmacology, University of Oxford, Oxford, OX1 3QT United Kingdom, trevor.sharp@pharm.ox.ac.uk marco.capogna@biomed.au.dk.
  • ,
  • Marco Capogna

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.

Original languageEnglish
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume37
Issue7
Pages (from-to)1785-1796
Number of pages12
ISSN0270-6474
DOIs
Publication statusPublished - 15 Feb 2017

    Research areas

  • 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

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