Fast-synaptic axo-axonal transmission from striatal cholinergic interneurons onto dopamine fibers.

Kramer, P. F.; Brill-Weil, S.; Cummins, A.; Zhang, R.; Camacho-Hernandez, G. A.; Newman, A. H.; Eldridge, M. A.; Averbeck, B. B.; Khaliq, Z. M.

doi:10.1101/2022.03.25.485828

bioRxiv · 10.1101/2022.03.25.485828

Fast-synaptic axo-axonal transmission from striatal cholinergic interneurons onto dopamine fibers.

Kramer, P. F.·Brill-Weil, S.·Cummins, A.·Zhang, R.·Camacho-Hernandez, G. A.·Newman, A. H.·Eldridge, M. A.·Averbeck, B. B.·Khaliq, Z. M.

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Abstract

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 6-containing receptors. Remarkably, axEPSPs triggered spontaneous action potentials locally in dopaminergic axons, suggesting these axons perform integration to convert synaptic input into spiking, a function associated with somatodendritic compartments. We investigated cross-species validity of cholinergic axo-axonal transmission by recording dopaminergic axons in macaque putamen and found similar axEPSPs. Thus, we reveal that fast synaptic-like neurotransmission underlies cholinergic signaling onto dopaminergic axons, providing insight into how nicotinic receptors shape electrical signaling directly in axon terminals.

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Kramer, P. F., Brill-Weil, S., Cummins, A., Zhang, R., Camacho-Hernandez, G. A., Newman, A. H., Eldridge, M. A., Averbeck, B. B., Khaliq, Z. M.. 2022-03-27. Fast-synaptic axo-axonal transmission from striatal cholinergic interneurons onto dopamine fibers.. https://doi.org/10.1101/2022.03.25.485828

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