Fast synaptic transmission in the goldfish CNS mediated by multiple nicotinic receptors

Non-technical summary Usually nicotinic receptors in the central nervous system only influence the strength of a signal between neurons. At a few critical connections, for instance some of those involved in the flight response, nicotinic receptors not only modulate the signal, they actually determine whether a signal is conveyed or not. We show at one of the few such connections accessible for study, up to three different nicotinic receptor subtypes mediate the signal. The subtypes appear to be clustered in separate locations. Depending on the number and combination of the subtypes present the signal can range from short to long duration and from low to high amplitude. This provides a critical connection with a built-in plasticity and may enable it to adapt to a changing environment.In this study, fast synaptic transmission at vertebrate CNS connections mediated by several different nicotinic ACh receptors (nAChRs) was investigated with paired recordings from pre- and postsynaptic neurons. Analysis of the response kinetics at the axo-axonic connections between the Mauthner (M-) axon and cranial relay neurons (CRN) indicates up to three main components are present and can be characterized by fast, similar to 1.5 ms, intermediate, similar to 6 ms and slow, similar to 15 ms, decay time constants. Further analysis indicates most responses have multiexponential decays and each response falls into one of six classes dependent on the weight and combination of kinetic components. Pharmacological results suggest that up to three nAChRs, alpha 7*, alpha 3 beta 2* and alpha 3 beta 4*, mediate the postsynaptic responses and correspond to the fast, intermediate and slow decay components, respectively. The fast decay component is blocked by similar to 35 nm methyllycaconitine (MLA), 100 nm alpha-bungarotoxin (alpha-Btx) or 150 nm alpha-conotoxin (alpha-Ctx) ArIB. The intermediate decay component is blocked by 2 mu m dihydro-beta-erythroidine (DH beta E) or 200 nm alpha-Ctx GIC. The slow decay component is blocked by 10 mu m alpha-Ctx AuIB, but not by 7.25 mu m DH beta E. Intriguingly, the mEPSPs (minis) at connections with evoked EPSPs best fitted by multiple exponentials, were not composite; rather, there were multiple populations of minis, each with single exponential decay times corresponding to those of the different evoked EPSP components. This indicates that the different receptors are topographically segregated at the connection between the M-axon and CRN axon. These results suggest that, as with glutamate, fast nicotinic synaptic transmission in the CNS can be mediated by multiple receptors in the same postsynaptic neuron. The coexistence of EPSPs of different durations may have implications for network function and plasticity.