Browse by author
Lookup NU author(s): Dr Mark EldridgeORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2022. Transmission from striatal cholinergic interneurons (CINs) controls dopamine release through nicotinic acetylcholine receptors (nAChRs) on dopaminergic axons. Anatomical studies suggest that cholinergic terminals signal predominantly through non-synaptic volume transmission. However, the influence of cholinergic transmission on electrical signaling in axons remains unclear. We examined axo-axonal transmission from CINs onto dopaminergic axons using perforated-patch recordings, which revealed rapid spontaneous EPSPs with properties characteristic of fast synapses. Pharmacology showed that axonal EPSPs (axEPSPs) were mediated primarily by high-affinity α6-containing receptors. Remarkably, axEPSPs triggered spontaneous action potentials, suggesting that these axons perform integration to convert synaptic input into spiking, a function associated with somatodendritic compartments. We investigated the cross-species validity of cholinergic axo-axonal transmission by recording dopaminergic axons in macaque putamen and found similar axEPSPs. Thus, we reveal that synaptic-like neurotransmission underlies cholinergic signaling onto dopaminergic axons, supporting the idea that striatal dopamine release can occur independently of somatic firing to provide distinct signaling.
Author(s): Kramer PF, Brill-Weil SG, Cummins AC, Zhang R, Camacho-Hernandez GA, Newman AH, Eldridge MAG, Averbeck BB, Khaliq ZM
Publication type: Article
Publication status: Published
Journal: Neuron
Year: 2022
Volume: 110
Issue: 18
Pages: 2949-2960.e4
Print publication date: 21/09/2022
Online publication date: 04/08/2022
Acceptance date: 12/07/2022
Date deposited: 19/02/2025
ISSN (print): 0896-6273
ISSN (electronic): 1097-4199
Publisher: Cell Press
URL: https://doi.org/10.1016/j.neuron.2022.07.011
DOI: 10.1016/j.neuron.2022.07.011
PubMed id: 35931070
Altmetrics provided by Altmetric
