Research Highlight: Vesicular Release Statistics and Unitary Postsynaptic Current at Single GABAergic Synapses
The functional role of synaptic docking sites has remained unclear. Taking advantage of the simple geometry of MLIs (Molecular Layer Interneurons) in cerebellar slice preparations, and of the large size of quantal synaptic currents at MLI-MLI synapses, ENP leader Alain Marty and colleagues have developed a novel method combining paired patch-clamp recording, statistical treatment of data and modeling to stimulate and record from individual synaptic sites. Their results suggest that individual synaptic sites contain a fixed small number of docking sites, and that in each synaptic site, the number of docking sites is an integrator of pre- and post-synaptic parameters and a potent organizer of synaptic function. Importantly enough, this work introduces docking site occupancy as a central player in synaptic physiology.
Vesicular Release Statistics and Unitary Postsynaptic Current at Single GABAergic Synapses. Camila Pulido, Federico F. Trigo, Isabel Llano, Alain Marty. Neuron 85, 159–172, January 7, 2015. DOI: http://dx.doi.org/10.1016/j.neuron.2014.12.006
Figure: Docking site number determines differences between single synapses.Pulido et al (2015) Neuron 85:159-172. MLI-MLI synapses were studied using paired patch-clamp recording, giving trains of presynaptic action potentials (vertical lines). Recordings display homogeneous peak amplitudes and occlusion between successive responses, indicating single synapses with one active zone (brown) and one postsynaptic density (green).
On the left the synapse has one docking site (blue: N = 1). Quantal amplitudes are relatively small, due to a small number of postsynaptic receptors. Failure rates are high, particularly in response to late stimulations, because all responses originate from a single docking site.
On the right the synapse has six docking site (N = 6). Quantal amplitudes are large, due to a large number of postsynaptic receptors. Failure rates are low, because several docking sites contribute to the responses. In spite of multivesicular release, response amplitudes reach a common peak, reflecting postsynaptic receptor saturation (dashed lines). Decay kinetics of synaptic currents are slower with N = 6 than with N = 1, due to a larger and longer transient of the neurotransmitter in the synaptic cleft after each action potential. These observations suggest that differences among single synapses follow a systematic pattern depending on docking site number.
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