TY  - GEN
T1  - Sarm1 is dispensable for mechanosensory-motor transformations in zebrafish
AU  - Asgharsharghi, Amir
AU  - Tian, Weili
AU  - Haehnel-Taguchi, Melanie
AU  - López-Schier, Hernán
DO  - 10.17912/micropub.biology.000369
UR  - http://beta.micropublication.org/journals/biology/micropub-biology-000369/
AB  - We have previously established that the anatomical structure of the lateral-line mechanosensory system in zebrafish is not affected by loss-of-function mutations in Sarm1 (Tian, W. et al., 2020; Tian, W. and López-Schier, H, 2020). Here we test whether the systemic loss of Sarm1 disrupts the transformation of mechanosensory input into neuronal function as well as behavioral motor output (Oteíza, P. et al., 2017). To this end, we used a sensitive assay consisting of a 100-millisecond mechanical stimulation of lateral-line neuromasts with a water jet and loose patch recordings from lateralis afferent neurons (Haehnel-Taguchi, M. et al., 2014). This experiment showed spontaneous and evoked neuronal activity in Sarm1 mutant and control larvae (Figure 1A). Although, in general spontaneous spike rate and signal-to-noise ratio can vary across recordings from lateralis afferent neurons, signal-to-noise ratio is lower in Sarm1 mutants compared to controls (Liao, J.C. and Haehnel, M., 2012). Raster plots from two stimulus protocols in control and Sarm1 larvae show that both reliably respond to repeated stimulation (Figure 1B). The spontaneous spike rates of lateralis neurons (Figure 1C) and the latency of response onset after stimulus presentation (Figure 1D) were not significantly different between control and mutants. Both, Sarm1 and control larvae respond with a significant increase in the spike rate to mechanical stimulation, however there was no significant difference in response strength between Sarm1 mutants and controls (Figure 1E). We found a remarkable difference in axonal regeneration, in that loss of Sarm1 significantly accelerated the growth rate of axons (Figure 1F). Next, we asked whether these mild differences of neuronal activity might impact the behavioral reaction of the fish to water flow that is mediated by the lateral line (Oteíza, P. et al., 2017). We conducted a rheotactic assay by exposing larval zebrafish to 6mm/s laminar water flow and measure their orientation to flow direction. We found that although rheotaxis did not fully recover in this experimental paradigm, the recovery by normal specimens was only marginally better than that of Sarm1 mutants (Figure 1G). Finally, we used the natural regeneration of the lateralis peripheral nerve to test the impact of systemic loss of Sarm1 on sensorimotor recovery after damage (Xiao, Y. and López-Schier, H. 2016). Unilateral abrogation of anterior and posterior lateral-line function completely eliminates rheotaxis under laminar flow (Oteíza, P. et al., 2017). Therefore, we severed all peripheral axon of the anterior and posterior lateral line on one side of larval zebrafish and tested rheotaxis 1 and 3 days afterwards, respectively 1 and 3 dpi. We confirmed that without lateral-line input 1 dpi, rheotaxis was severely disrupted in wild-type and Sarm1-mutant larvae (Figure 1G), and found that rheotaxis partially recovered 3 dpi, with no significant difference between wild-type and Sarm1 mutants. Our data predict that systemic inhibition of Sarm1 is a viable option for therapeutic application in humans (Henninger, N. et al., 2026; Sasaki, Y. et al., 2020; Hughes, R.O., et al., 2021).
PY  - 2021
JO  - microPublication Biology
ER  -