The Journal of Neuroscience, March 15, 2001, 21(6):1857-1867
1 Neuroscience Training Program, University of
Wisconsin, Madison, Wisconsin 53706, and 2 Oregon Hearing
Research Center and Vollum Institute, Oregon Health Sciences
University, Portland, Oregon 97201
Transmission at the end-bulb synapse formed by auditory nerve
terminals onto the soma of neurons in the avian nucleus magnocellularis is characterized by high transmitter release probability and strong synaptic depression. Activation of presynaptic GABAB
receptors minimizes depression at this synapse and significantly
enhances synaptic strength during high-frequency activity. Here we
investigate synaptic mechanisms underlying this phenomenon. EPSC
amplitudes evoked by 200 Hz trains increased more than twofold when
release probability was reduced with Cd2+ or
baclofen. This effect was not exhibited by a transmitter depletion model of presynaptic depression, which predicts that EPSC amplitudes reach a common steady-state amplitude during high-frequency trains, despite alterations of initial release probability. However, an additional source of postsynaptic depression was sufficient to explain
our findings. Aniracetam, a modulator of AMPA receptors that reduces
desensitization, decreased the amount of synaptic depression during
trains, indicating that desensitization occurred during trains of
stimuli. However, this effect of aniracetam was absent when release
probability was lowered with baclofen or Cd2+. No
effect of aniracetam on the NMDA component of the EPSC was seen,
confirming a postsynaptic site of action of aniracetam. When
desensitization was reduced with aniracetam, steady-state EPSC
amplitudes during trains were found to converge over a wide range of
release probabilities, as predicted by the depletion model. Additional
evidence of AMPA receptor desensitization was provided by direct
measurement of quantal amplitudes immediately after stimulus trains.
Thus, presynaptic modulation by GABAB receptors regulates
the extent of AMPA receptor desensitization and controls synaptic
strength, thereby modulating the flow of information at an auditory synapse.
Key words: short-term depression; AMPA receptors; desensitization; cochlear nucleus; GABAB receptors; end-bulb synapse; auditory