Researchers use X-ray microscopy with ZEISS Xradia Versa to identify regions of interest for SBF-SEM with ZEISS GeminiSEM to image noise-related alterations with and without noise-exposure history.

Acoustic information is encoded into neural signals in the cochlea, the mammalian hearing organ in the inner ear. Sound encoding, which occurs at the synaptic connections between inner hair cells (IHCs) and postsynaptic spiral ganglion neurons (SGNs), faithfully preserves signal features such as frequency, intensity, and timing.

Dr. Yunfeng Hua is a Professor at Shanghai Jiao Tong University School of Medicine and Principal investigator at Shanghai Institute of Precision Medicine, Shanghai Ninth People’s Hospital, China. His team is interested in synapse morphology and uses volume electron microscopy techniques to uncover pathological mechanisms behind brain dysfunctions and diseases.

In their recent work, they use X-ray microscopy to identify key regions of interest for in-depth, high-resolution, serial block-face scanning electron microscopy (SBF-SEM) imaging to comprehend noise-related alterations in cochlear structures by comparing the spatial patterns of synapse morphology between cochleae with and without noise-exposure history. They report several key observations using these content-rich volume electron microscopy datasets, advancing our current understanding of the pathology behind noise-induced hearing loss.

Different sound frequencies can activate IHCs at varying cochlear positions. It is critical to localize the targeted cells at the whole cochlea level for structural investigation. X-ray microscopy allows us to precisely determine the regions of interest and plan sample preparation for SBF-SEM.

Dr. Yunfeng Hua (shown center with lab members)

In the noise-exposed cochlea, Dr. Hua and his team observed mixed spatial patterns of synapse degeneration accompanied by dramatic morphological changes in the survived synapses. This argues for some sort of neuronal activity-dependent synaptic adaptation and reorganization in the IHC, rather than random elimination of individual synapses.

Moreover, the noise-resistant synapses appear to have enriched mitochondria in the postsynaptic terminal, likely providing a sufficient calcium uptake capacity to alleviate the excitotoxicity.

Although we captured the hallmarks of noise-vulnerable synapses in the cochlea, it remains for future investigations how such synaptic heterogeneity is established and maintained. Our ongoing work is to seek cytoarchitectural insights by reconstructing all the functional organelles in the pre- and postsynaptic cells. Volume electron microscopy will play a key role in this.