Work

Patterned pre-sensory spontaneous activity drives the structural refinement of developing cochlear ribbon synapses

Year: 2026

Type: article

Abstract: Introduction: In the mammalian cochlea, hearing relies on highly specialized ribbon-type synapses between sensory inner hair cells (IHCs) and postsynaptic spiral ganglion neurons. During early postnatal maturation, structural and functional refinements re-shape synaptic morphology and thereby maximize release efficiency in the run-up to hearing onset. This developmental period is further characterized by the occurrence of pre-sensory spontaneous activity waves, which are essential for the functional maturation of the ascending auditory pathway- yet, their importance for IHC presynaptic structural refinement remains uncertain. Methods: To investigate activity-dependent structural plasticity at cochlear ribbon synapses, we combined genetic, pharmacological, and optogenetic approaches with immunohistochemical and electrophysiological analyses. Moreover, we developed a novel optical stimulation device (OSD) that enables millisecond-precise, long-term and differentially-patterned optogenetic activation of cochlear IHCs under tightly controlled conditions within a standard tissue culture incubator. Results: Using this experimental framework, we show that positive as well as negative activity modulation triggers dynamic and rapidly-inducible homeostatic scaling of ribbon synapse morphology. Moreover, our data indicate that the temporal pattern of the presynaptic activity acts as a fundamental regulatory component of this process. Discussion: Our results suggest that - prior to hearing onset - pre-sensory synaptic activity plays a critical role in shaping cochlear ribbon synapse architecture in the developing auditory system.

Source: Frontiers in Synaptic Neuroscience

DOI: 10.3389/fnsyn.2026.1730181