5-HT7 receptors enhance inhibitory synaptic input to principal neurons in the mouse basal amygdala. (15th October 2021)

• Record Type: Journal Article
• Authors: Kusek, Magdalena; Siwiec, Marcin; Sowa, Joanna Ewa; Bobula, Bartosz; Bilecki, Wiktor; Ciurej, Izabela; Kaczmarczyk, Maria; Kowalczyk, Tomasz; Maćkowiak, Marzena; Hess, Grzegorz; Tokarski, Krzysztof
• Is Part Of: Neuropharmacology. Volume 198(2021)
• Publication Date: 2021-10-15
• Subjects: Basal amygdala -- 5-HT7 receptor knockout mice -- Htr7-EGFP mice -- 5-HT7 receptor antagonist -- GABAergic interneurons; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2021.108779
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: The basal amygdala (BA) has been implicated in encoding fear and its extinction. The level of serotonin (5-HT) in the BA increases due to arousal and stress related to aversive stimuli. The effects of 5-HT7 receptor (5-HT7 R) activation and blockade on the activity of BA neurons have not yet been investigated. In the present study, a transgenic mouse line carrying green fluorescent protein (GFP) reporter gene was used to identify neurons that express the 5-HT7 R. GFP immunoreactivity was present mainly in cells that also expressed GAD67 or parvalbumin (PV), the phenotypic markers for GABAergic interneurons. Most cells showing GFP fluorescence demonstrated firing patterns characteristic of BA inhibitory interneurons. Activation of 5-HT7 Rs resulted in a depolarization and/or occurrence of spontaneous spiking activity of BA interneurons that was accompanied by an increase in the mean frequency and mean amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from BA principal neurons. These effects were blocked by a specific 5-HT7 R antagonist, SB269970 and were absent in slices from 5-HT7 R knockout mice. Activation of 5-HT7 Rs also decreased the mean frequency of spontaneous excitatory postsynaptic currents (sEPSCs) recorded from BA principal neurons, which was blocked by the GABAA receptor antagonist picrotoxin. Neither inhibitory nor excitatory miniature postsynaptic currents (mIPSCs/mEPSCs) were affected by 5-HT7 R activation. These results show that in the BA 5-HT7 Rs stimulate an activity-dependent enhancement of inhibitory input from local interneurons to BA principal neurons and provide insights about the possible involvement of BA serotonergic receptors in neuronal mechanisms underlying fear memory. Graphical abstract: Image 1 Highlights: In the mouse basal amygdala (BA) 5-HT7 receptors are present primarily on GABAergic interneurons but not on principal neurons. Application of 5-HT7 receptor agonist induces depolarization and spontaneous spiking activity in BA GABAergic interneurons. Activation of 5-HT7 receptors on interneurons increases frequency and amplitude of spontaneous IPSCs in BA principal neurons. Activation of 5-HT7 receptors also decreased the mean frequency of spontaneous EPSCs recorded from BA principal neurons. The effects of the activation of 5-HT7 receptors in the BA of wild-type mice are absent in 5-HT7 receptor knockout mice.