| First Author | Kramer PF | Year | 2022 |
| Journal | Neuron | Volume | 110 |
| Issue | 18 | Pages | 2949-2960.e4 |
| PubMed ID | 35931070 | Mgi Jnum | J:329330 |
| Mgi Id | MGI:7343507 | Doi | 10.1016/j.neuron.2022.07.011 |
| Citation | Kramer PF, et al. (2022) Synaptic-like axo-axonal transmission from striatal cholinergic interneurons onto dopaminergic fibers. Neuron 110(18):2949-2960.e4 |
| abstractText | 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 alpha6-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. |
