Direct activation of the Mauthner cell by electric field pulses drives ultrarapid escape responses

Abstract

Rapid escape swims in fish are initiated by the Mauthner cells, giant reticulospinal neurons with unique specializations for swift responses. The Mauthner cells directly activate motoneurons and facilitate predator detection by integrating acoustic, mechanosensory, and visual stimuli. In addition, larval fish show well-coordinated escape responses when exposed to electric field pulses (EFPs). Sensitization of the Mauthner cell by genetic overexpression of the voltage-gated sodium channel SCN5 increased EFP responsiveness, whereas Mauthner ablation with an engineered variant of nitroreductase with increased activity (epNTR) eliminated the response. The reaction time to EFPs is extremely short, with many responses initiated within 2 ms of the EFP. Large neurons, such as Mauthner cells, show heightened sensitivity to extracellular voltage gradients. We therefore tested whether the rapid response to EFPs was due to direct activation of the Mauthner cells, bypassing delays imposed by stimulus detection and transmission by sensory cells. Consistent with this, calcium imaging indicated that EFPs robustly activated the Mauthner cell but only rarely fired other reticulospinal neurons. Further supporting this idea, pharmacological blockade of synaptic transmission in zebrafish did not affect Mauthner cell activity in response to EFPs. Moreover, Mauthner cells transgenically expressing a tetrodotoxin (TTX)-resistant voltage-gated sodium channel retained responses to EFPs despite TTX suppression of action potentials in the rest of the brain. We propose that EFPs directly activate Mauthner cells because of their large size, thereby driving ultrarapid escape responses in fish.

Left Habenular Activity Attenuates Fear Responses in Larval Zebrafish

“…Electric field stimulation (EFS; Figure S1A) induces three clearly distinguishable phases: (i) immediate hyperactivity [10], followed by (ii) a short period of inactivity and, finally, (iii) resumption of swimming (Movie S1). To establish the optimal stimulation intensity, larval responses to shock were measured across voltage intensities ranging from 0–100 V. Decreased locomotor activity post-shock, measured by the change in total distance traveled, as well as increased levels of the stress hormone, cortisol, were proportional to the intensity of the shock (Figure S1B, C).…”

Visual Threat Assessment and Reticulospinal Encoding of Calibrated Responses in Larval Zebrafish

“…Mauthner cells collect sensory information from one side of the body and transmit it to the other side via a large caliber axon [8, 9], resulting in a strong contraction of body muscles opposite to the stimulus that generates a short-latency evasive turn. Mauthner cells respond to visual, tactile, vestibular, auditory, lateral-line and electric field stimuli [10, 11, 12, 13, 14, 15] and are difficult to excite [16, 17, 18]. The conclusion from these studies across various modalities is that the decision to escape is a result of reaching the Mauthner cell firing threshold due to strong sensory input, as would arise from an approaching predator that has traversed the proximity threshold.…”

Genetic Ablation, Sensitization, and Isolation of Neurons Using Nitroreductase and Tetrodotoxin-Insensitive Channels

“…However the best characterized system relies on expression of the bacterial nitroreductase, NfsB , which metabolizes bath applied metronidazole into a cell-impermeant cytotoxin [9–11]. This system allows temporal control of ablation through metronidazole exposure and has recently been optimized to yield robust neuronal ablation within 24 hours [12–13]. A simple way to verify that metronidazole treatment induces apoptosis is to use PhiPhiLux G1D2, a live fluorescent reporter of caspase 3-like activity [14].…”

“…Moreover, induced firing patterns may not reproduce normal patterns of neuronal activation. An alternate method is to over-express a voltage-gated sodium channel in neurons of interest, thereby increasing their sensitivity to endogenous patterns of depolarizing input [13]. Specific changes in behavioral measures in transgenic fish can thus reveal the contribution of sensitized neurons.…”