Determining synaptic parameters using high-frequency activation
Autor: | Monica S. Thanawala, Wade G. Regehr |
---|---|
Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Male Patch-Clamp Techniques Biology Neurotransmission Article Synapse 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Synaptic augmentation Animals Neurotransmitter General Neuroscience Excitatory Postsynaptic Potentials Synapsin Synaptic Potentials Mice Inbred C57BL 030104 developmental biology chemistry Synaptic plasticity Synapses Excitatory postsynaptic potential Female Calyx of Held Neuroscience 030217 neurology & neurosurgery Brain Stem |
Zdroj: | Journal of neuroscience methods. 264 |
ISSN: | 1872-678X |
Popis: | Background The specific properties of a synapse determine how neuronal activity evokes neurotransmitter release. Evaluating changes in synaptic properties during sustained activity is essential to understanding how genetic manipulations and neuromodulators regulate neurotransmitter release. Analyses of postsynaptic responses to high-frequency stimulation have provided estimates of the size of the readily-releasable pool (RRP) of vesicles (N0) and the probability of vesicular release (p) at multiple synapses. New method Here, we introduce a model-based approach at the calyx of Held synapse in which depletion and the rate of replenishment (R) determine the number of available vesicles, and facilitation leads to a use-dependent increase in p when initial p is low. Results When p is high and R is low, we find excellent agreement between estimates based on all three methods and the model. However, when p is low or when significant replenishment occurs between stimuli, estimates of different methods diverge, and model estimates are between the extreme estimates provided by the other approaches. Comparison with other methods We compare our model-based approach to three other approaches that rely on different simplifying assumptions. Our findings suggest that our model provides a better estimate of N0 and p than previously-established methods, likely due to inaccurate assumptions about replenishment. More generally, our findings suggest that approaches commonly used to estimate N0 and p at other synapses are often applied under experimental conditions that yield inaccurate estimates. Conclusions Careful application of appropriate methods can greatly improve estimates of synaptic parameters. |
Databáze: | OpenAIRE |
Externí odkaz: |