in-vivo-calcium-imaging-of-lateral-line-hair-cells-in-larval-zebrafish

In Vivo Calcium Imaging of Lateral-line Hair Cells in Larval Zebrafish

Sensory hair cells are mechanoreceptors found in the inner ear that are required for hearing and balance. Hair cells are activated in response to sensory ...

NIDCD/National Institutes of Health

In sensory hair cells of auditory and vestibular organs, the ribbon synapse is required for the precise encoding of a wide range of complex stimuli. Hair cells have a unique presynaptic structure, the synaptic ribbon, which organizes both synaptic vesicles and calcium channels at the active zone. Previous work has shown that hair-cell ribbon size is correlated with differences in postsynaptic activity. However, additional variability in postsynapse size presents a challenge to determining the specific role of ribbon size in sensory encoding. To selectively assess the impact of ribbon size on synapse function, we examined hair cells in transgenic zebrafish that have enlarged ribbons, without postsynaptic alterations. Morphologically, we found that enlarged ribbons had more associated vesicles and reduced presynaptic calcium-channel clustering. Functionally, hair cells with enlarged ribbons had larger global and ribbon-localized calcium currents. Afferent neuron recordings revealed that hair cells with enlarged ribbons resulted in reduced spontaneous spike rates. Additionally, despite larger presynaptic calcium signals, we observed fewer evoked spikes with longer latencies from stimulus onset. Together, our work indicates that hair-cell ribbon size influences the spontaneous spiking and the precise encoding of stimulus onset in afferent neurons. Numerous studies support that hair-cell ribbon size corresponds with functional sensitivity differences in afferent neurons and, in the case of inner hair cells of the cochlea, vulnerability to damage from noise trauma. Yet it is unclear whether ribbon size directly influences sensory encoding. Our study reveals that ribbon enlargement results in increased ribbon-localized calcium signals, yet reduces afferent spontaneous activity and disrupts the timing of stimulus onset, a distinct aspect of auditory and vestibular encoding. These observations suggest that varying ribbon size alone can influence sensory encoding, and give further insight into how hair cells transduce signals that cover a wide dynamic range of stimuli.

Enlargement of Ribbons in Zebrafish Hair Cells Increases Calcium Currents But Disrupts Afferent Spontaneous Activity and Timing of Stimulus Onset.

Analysis of mechanotransduction among ensembles of sensory hair cells in vivo is challenging in many species. To overcome this challenge, we used optical indicators to investigate mechanotransduction among collections of hair cells in intact zebrafish. Our imaging reveals a previously undiscovered disconnect between hair-cell mechanosensation and synaptic transmission. We show that saturating mechanical stimuli able to open mechanically gated channels are unexpectedly insufficient to evoke vesicle fusion in the majority of hair cells. Although synaptically silent, latent hair cells can be rapidly recruited after damage, demonstrating that they are synaptically competent. Therefore synaptically silent hair cells may be an important reserve that acts to maintain sensory function. Our results demonstrate a previously unidentified level of complexity in sculpting sensory transmission from the periphery.

Synaptically silent sensory hair cells in zebrafish are recruited after damage.

Sensorineural hearing loss is the most common form of hearing loss in humans, and results from either dysfunction in hair cells, the sensory receptors of sound, or the neurons that innervate hair cells. A specific type of sensorineural hearing loss, referred to as auditory synaptopathy, occurs when hair cells are able to detect sound but fail to transmit sound stimuli at the hair-cell synapse. Auditory synaptopathy can originate from genetic alterations that specifically disrupt hair-cell synapse function. Additionally, environmental factors such as noise exposure can leave hair cells intact but result in loss of hair-cell synapses, and represent an acquired form of auditory synaptopathy. The zebrafish model has emerged as a valuable system for studies of hair-cell function, and specifically hair-cell synaptopathy. In this review, we describe the experimental tools that have been developed to study hair-cell synapses in zebrafish. We discuss how zebrafish genetics has helped identify and define the roles of hair-cell synaptic proteins crucial for hearing in humans, and highlight how studies in zebrafish have contributed to our understanding of hair-cell synapse formation and function. In addition, we also discuss work that has used noise exposure or pharmacological mimic of noise-induced excitotoxicity in zebrafish to define cellular mechanisms underlying noise-induced hair-cell damage and synapse loss. Lastly, we highlight how future studies in zebrafish could enhance our understanding of the pathological processes underlying synapse loss in both genetic and acquired auditory synaptopathy. This knowledge is critical in order to develop therapies that protect or repair auditory synaptic contacts.

Article	Year
Enlargement of Ribbons in Zebrafish Hair Cells Increases Calcium Currents But Disrupts Afferent Spontaneous Activity and Timing of Stimulus Onset. The Journal of neuroscience : the official journal of the Society for Neuroscience\| PubMed ID: 28546313	2017
Synaptically silent sensory hair cells in zebrafish are recruited after damage. Nature communications\| PubMed ID: 29643351	2018
Transmission Disrupted: Modeling Auditory Synaptopathy in Zebrafish. Frontiers in cell and developmental biology\| PubMed ID: 30258843	2018

Katie S. Kindt

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