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April 4th, 2025
Version: 1
National Autonomous University of Mexico
neuroscience
biorxiv

Novel multi-transmitter calyx-like giant synapse revealed in the extended amygdala

Zhang, L.Open in Google Scholar•Hernandez, V.Open in Google Scholar•Giraldo, D. M.Open in Google Scholar•Leon-Contreras, J. C.Open in Google Scholar•Ye, R.Open in Google Scholar•Zhang, S.Open in Google Scholar•Schafer, M. K.-H.Open in Google Scholar•barrio, r.Open in Google Scholar•Hernandez-Pando, R.Open in Google Scholar•Ferraguti, F.Open in Google Scholaret al.

The calyx of Held, a giant excitatory cup-like axo-somatic synapse, has been historically described exclusively in the auditory brainstem. Here, using PACAP immunohistochemistry combined with confocal and tomographic electron microscopy, we report the discovery of a morphologically similar calyx-like synapse in the extended amygdala of rodents, exhibiting unique neurochemical features. This previously unrecognized structure forms massive axo-somatic terminals with mixed glutamatergic and cholinergic identities, co-expressing VGluT1, VGluT2, VAChT, and the neuropeptides PACAP, CGRP, and neurotensin, along with calretinin in the presynaptic compartment. The postsynaptic targets are a distinct subset of PKC{delta}-expressing neurons that co-express the synaptic adhesion molecule GluD1. Strikingly, GluD1 immunolabeling is concentrated specifically at axo-somatic contact sites apposed to VAChT+ calyceal terminals, but absent at PSD of conventional type I synapse, suggesting a specialized molecular architecture for calyceal synapse. Our findings reveal a previously unknown calyx-like synapse in the forebrain, exhibiting a unique convergence of fast and modulatory transmission with implications for transmission fidelity within emotional-viscerosensory circuits.

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