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

• DOI: 10.1523/jneurosci.2238-16.2016
• Publication Date: 2017-01-14T03:00:29Z
• Authors: Ayesha Sengupta; Marco Bocchio; David M. Bannerman; Trevor Sharp; Marco Capogna
• Keywords: Channelrhodopsin

The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines evidence suggest that 5-HT transmission in is implicated susceptibility drug treatment mood disorders. Therefore, elucidating physiological mechanisms through which midbrain neurons modulate circuits could be pivotal understanding regulation health disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal (BA) brain slices mice with channelrhodopsin genetically targeted to neurons. Optical stimulation terminals at low frequencies (≤1 Hz) evoked a short-latency excitation BA interneurons (INs) was depressed higher frequencies. Pharmacological analysis revealed this effect mediated by glutamate not because it abolished ionotropic receptor antagonists. (10–20 both slow inhibition INs. These effects were they blocked antagonists 2A 1A receptors, respectively. fast glutamate- 5-HT-mediated responses often coexisted same neuron. Interestingly, fast-spiking non-fast-spiking INs displayed differential modulation 5-HT. Furthermore, optical did evoke release onto principal neurons, but inhibited cells directly via activation receptors indirectly enhanced GABA release. Collectively, findings exert frequency-dependent, cell-type-specific control over circuitry co-release inhibit output. SIGNIFICANCE STATEMENT important for pathogenesis affective essential determine dorsal raphe nuclei circuits. Here, combined optogenetic, electrophysiological, pharmacological approaches study axons nucleus (BA). We found frequency-dependent manner. theories contribution function should revised incorporate concept 5-HT/glutamate cotransmission.