bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/452524

Developmental synaptic changes at the transient olivocochlear-inner hair cell synapse

Kearney, G.·Zorrilla de San Martin, J.·Vattino, L. G.·Elgoyhen, A. B.·Wedemeyer, C.·Katz, E.
View original source ↗Export metadata ↓

Abstract

In the mature mammalian cochlea, inner hair cells (IHCs) are mainly innervated by afferent fibers that convey sound information to the central nervous system. During postnatal development, however, medial olivocochlear (MOC) efferent fibers transiently innervate the IHCs. The MOC-IHC synapse, functional from postnatal day (P)0 to hearing onset (P12), undergoes dramatic changes in the sensitivity to acetylcholine (ACh) and in the expression of key postsynaptic proteins. To evaluate whether there are associated changes in the properties of ACh release during this period, we used a cochlear preparation from mice at P4, P6-7 and P9-11 and monitored transmitter release from MOC terminals in voltage-clamped IHCs in the whole-cell configuration. The quantum content increased 5.6x from P4 to P9-11 due to increases in the size and replenishment rate of the readily releasable pool (RRP) of synaptic vesicles, without changes in their probability of release (Pvesicle) or quantum size. This strengthening in transmission was accompanied by changes in the short-term plasticity (STP) properties, which switched from facilitation at P4 to depression at P9-11. We have previously shown that at P9-11, ACh release is supported by P/Q and N-type voltage-gated calcium channels (VGCCs) and negatively regulated by BK potassium channels activated by Ca2+ influx through L-type VGCCs. We now show that at P4 and P6-7, release is mediated by P/Q-, R- and L-type VGCCs. Interestingly, L-type VGCCs have a dual role: they both support release and fuel BK channels, suggesting that at immature stages the presynaptic proteins involved in release are less compartmentalized.\n\nSignificance statementDuring postnatal development prior to the onset of hearing, cochlear IHCs present spontaneous Ca2+ action potentials which release glutamate at the first auditory synapse in the absence of sound stimulation. The IHC Ca2+ action potential frequency pattern, which is crucial for the correct establishment and function of the auditory system, is regulated by the efferent MOC system that transiently innervates IHCs during this period. We show short-term synaptic plasticity properties of the MOC-IHC synapse that tightly shape this critical developmental period.

Source connections

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Kearney, G., Zorrilla de San Martin, J., Vattino, L. G., Elgoyhen, A. B., Wedemeyer, C., Katz, E.. 2018-10-24. Developmental synaptic changes at the transient olivocochlear-inner hair cell synapse. https://doi.org/10.1101/452524

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

40 Hz visual stimulation increases gamma-band functional connectivity between visual, parietal and frontal regions

Visual stimulation at 40 Hz is being investigated as a non-invasive intervention for Alzheimer's disease. Its neural responses have been reported in regions beyond the visual cortex, and concurrent cognitive tasks have been shown to increase their spatial extent. However, it is unclear whether these responses reflect increased functional connectivity between regions or a common response to the stimulus, and whether a concurrent task changes this connectivity. We recorded EEG from 29 healthy young adults during Regular 40 Hz flicker and Irregular 30-50 Hz flicker, each with and without a target-counting task (2 x 2 within-participant design). Source-space connectivity between visual, parietal, and frontal regions was estimated with the debiased squared weighted phase-lag index (dWPLI). Regular stimulation increased 38-42 Hz connectivity for all three region pairs, with the largest increase between visual and parietal regions (increase in all 29 participants). The increase was specific to the stimulation frequency and was observed with two source reconstruction methods and in sensor space. The visual-parietal increase remained significant after correction for source leakage (spatial mixing between reconstructed sources) and after removal of the estimated stimulus-locked component, whereas the increases in visual-frontal and parietal-frontal connectivity did not. The concurrent task did not modulate the visual-parietal effect. For visual-frontal and parietal-frontal connectivity, the stimulation-by-ask interaction was not significant. These results show that 40 Hz visual stimulation increases gamma-band connectivity beyond the visual cortex, and much of this increase reflects a common stimulus-locked response, and connectivity beyond this response was observed mainly between visual and parietal regions.

neuroscience↗
bioRxiv2026

Feedback Valence, Prediction Error, and the Limits of Computational Attribution in Symptom-Related EEG

Feedback-locked electroencephalography (EEG) responses are often interpreted using model-derived prediction errors (PEs), although signed PE can be strongly coupled to feedback valence in binary-outcome tasks. We revisited a published anxiety-related EEG association using two open probabilistic-learning datasets to examine measurement reliability, predictor separability, and participant-level recovery. In the primary dataset, greater trait anxiety was associated with a larger negative-minus-positive FCz theta response among 46 participants with elevated depressive symptoms after adjustment for depression severity. The association also differed between the sampled depression-symptom groups. The feedback contrast showed useful within-session reliability, but matched delta and P3-minus-N2 analyses did not establish theta specificity. Within participants, feedback valence and signed PE were highly correlated (r = -0.964). Exact-design simulations showed that population-level model discrimination could succeed despite poor recovery of individual neural slopes. Participant-specific learning-model refits recovered overall signed PE more consistently than the within-valence variation needed to distinguish it from feedback valence. An independent dataset reproduced the FCz feedback contrast in untreated and placebo cohorts but lacked trait-anxiety scores. Adding signed PE to valence yielded a small held-out predictive improvement under one reinforcement-learning specification, with limited support across sessions and no comparable support under the dual-rate model or in placebo. Together, these findings support a symptom-related feedback EEG association while constraining its theta-specific and participant-level computational interpretation.

neuroscience↗
bioRxiv2026

An open-access neuroimaging-compatible virtual town task for assessing human spatial navigation

Spatial navigation is a cognitive skill that draws on multiple processes such as learning, decision-making and memory, which are often updated on a second-by-second timescale. However, many existing virtual paradigms designed to assay spatial navigation cannot target these processes as they unfold or are not designed for integration with concurrent neurophysiological recording. Here, we present and demonstrate our open-access task for neuroimaging: NAturalistic Virtual Assessment of Navigation (NAVAN) combining high-resolution behavioural tracking and integration with electroencephalography. We report data from this task, in which fifty-three participants completed a wayfinding navigation paradigm across twenty-four trials. Navigational efficiency improved significantly following repeated exposure to the environment, although efficiency declined across trials within each block. Self-reported spatial ability (assessed by the Santa Barbara Sense of Direction) predicted performance during early environmental exposure, suggesting concurrent validity. We demonstrated the feasibility of recording electroencephalography during the task, with in-game events streamed and aligned to the neural recording. The task provides researchers with access to detailed behavioural measures and can be adapted by modifying features such as trial number and difficulty. We also provide a step-by-step implementation guide to support reuse and customisation across experimental settings.

neuroscience↗