Moss, GWJ;
Robertson, AD;
Caldwell, M;
Benton, DCH;
Smart, TG;
(2013)
Nanoscale-targeted patch-clamp recordings of functional presynaptic ion channels.
Neuron
, 79
(6)
1067- 1077.
10.1016/j.neuron.2013.07.012.
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Abstract
Important modulatory roles have been attributed to presynaptic NMDA receptors (NMDARs) located on cerebellar interneuron terminals. Evidence supporting a presynaptic location includes an increase in the frequency of mini events following the application of NMDA and gold particle-labelled NMDA receptor antibody localisation. However, more recent work, using calcium indicators, casts doubt on the idea of presynaptic NMDARs because basket cell varicosities did not show the expected calcium rise following either the local iontophoresis of L-aspartate or the two-photon uncaging of glutamate. (In theory such calcium imaging is sensitive enough to detect the calcium rise from even a single activated receptor.) It has therefore been suggested that the effects of NMDA are mediated via the activation of somatodendritic channels, which subsequently cause a subthreshold depolarization of the axon. Here we report results from a vibrodissociated preparation of cerebellar Purkinje cells, in which the interneuron cell bodies are no longer connected but many of their terminal varicosities remain attached and functional. This preparation can retain both inhibitory and excitatory inputs. We find that the application of NMDA increases the frequency of both types of synaptic event. The characteristics of these events suggest they can originate from interneuron, parallel fiber and even climbing fiber terminals. Interestingly, retrograde signalling seems to activate only the inhibitory terminals. Finally, antibody staining of these cells shows NMDAR-like immunoreactivity co-localised with synaptic markers. Since the Purkinje cells show no evidence of postsynaptic NMDAR-mediated currents, we conclude that functional NMDA receptors are located on presynaptic terminals.
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