Mechanisms and functional consequences of presynaptic homeostatic plasticity at auditory nerve synapses

Abstract

Multiple forms of homeostasis influence synaptic function under diverse activity conditions. Both presynaptic and postsynaptic forms of homeostasis are important, but their relative impact on fidelity is unknown. To address this issue, we studied auditory nerve synapses onto bushy cells in the cochlear nucleus of mice of both sexes. These synapses undergo bidirectional presynaptic and postsynaptic homeostatic changes with increased and decreased acoustic stimulation. We found that both young and mature synapses exhibit similar activity-dependent changes in short-term depression. Experiments using chelators and imaging both indicated that presynaptic Ca21 influx decreased after noise exposure, and increased after ligating the ear canal. By contrast, Ca21 cooperativity was unaffected. Experiments using specific antagonists suggest that occlusion leads to changes in the Ca21 channel subtypes driving neurotransmitter release. Furthermore, dynamic-clamp experiments revealed that spike fidelity primarily depended on changes in presynaptic depression, with some contribution from changes in postsynaptic intrinsic properties. These experiments indicate that presynaptic Ca21 influx is homeostatically regulated in vivo to enhance synaptic fidelity.