Lifting the mask of depression to reveal augmentation of transmitter release at physiological quantal content

Date of Award




Degree Name

Doctor of Philosophy (Ph.D.)

First Committee Member

Karl L. Magleby, Committee Chair


Repetitive stimulation leads to changes in transmitter release at most synapses. Augmentation, a process of increased transmitter release that decays with a time constant of ∼7 s, is readily apparent under conditions of low quantal content (with ∼0.4 mM Ca2+ and 5 mM Mg 2+ in the bathing solution). My study investigates if augmentation is present under conditions of normal and increased quantal content at the frog neuromuscular junction after conditioning stimulation at 20Hz (with 2--4 mM Ca2+ and 5 mM Mg2+). It was not possible to detect augmentation at normal and elevated levels of transmitter release using traditional methods of analysis because the large amounts of depression associated with the increased levels of release masked any augmentation present. Consequently, empirical models were fitted to the EPP amplitudes after the conditioning trains to estimate the components of augmentation, potentiation, and depression. Using these methods a component with a time constant consistent with augmentation was detected in ∼30--60% of experiments, depending on the assumptions of the model. This augmentation-like component was then identified as augmentation, as it displayed, in addition to its time constant, three other properties that characterize augmentation at low quantal content. Its magnitude was increased by 0.5--2 mM Ba2+, its decay correlated with the decay of residual Ca2+ or Ba2+ or both in the nerve terminal (measured with fluorescent imaging), and its underlying mechanism was an increase in the efficacy of synaptic vesicle release rather than an increase in the number of synaptic vesicles immediately available for release. The augmentation component could also be observed directly at normal quantal content after correcting the data for depression, determined by measuring the readily releasable pool of transmitter, and correcting the EPP amplitudes after the train. My findings indicate augmentation is a process that contributes to transmitter release over all ranges of quantal content. Augmentation, with a time constant similar to that of the fast component of depression, may counteract the effects of depression, allowing transmitter release to be maintained during repetitive stimulation.


Biology, Neuroscience

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