Excitatory/inhibitory balance of serotonergic axon connectivity in the brain

Serotonin neurons originate from the brainstem raphe nuclei and innervate the entire brain to regulate mood, emotion, sleep, appetite and aggression. Previous electron microscopy (EM) studies have revealed that 5-HT boutons directly contact several neuronal populations via asymmetrical (excitatory) or symmetrical (inhibitory) synapses. Additionally, 5-HT boutons sometimes form “triads” with the pre and postsynaptic components of asymmetrical or symmetrical synapses to modulate their activity. However, the exact proportion and distribution of 5-HT excitatory/inhibitory synapses and triads within the entire brain remains poorly described. Recently, we have published a novel semi-quantitative approach which combines fluorescent confocal microscopy and 3D reconstruction of 5-HT fibers apposed to excitatory and inhibitory neurochemical synapses (triads). Here, we review the similarities and differences in the distribution of 5-HT asymmetrical/symmetrical synapses observed in EM and the distribution of 5-HT excitatory/inhibitory triads quantified in our recent study. We further put into perspective the possible physiological role played by 5-HT triads in the regulation of glutamate and GABA signaling in these various brain regions. Excitatory/inhibitory balance of serotonergic axon connectivity in the brain Arnauld Belmer1, Vanessa Lanoue3, Omkar L. Patkar1, and Selena E. Bartlett1,2 1Translational Research Institute, Queensland University of Technology (QUT), Brisbane, Australia 2Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology (QUT), Brisbane, Australia 3Queensland Brain Institute (QBI), The University of Queensland, Brisbane, Australia