Audiovisual integration in the Mauthner cell enhances escape probability and reduces response latency

Fast and accurate threat detection is critically important for animal survival. Reducing perceptual ambiguity by integrating multiple sources of sensory information can enhance threat detection and reduce response latency. However, studies showing a direct link between behavioral correlates of multisensory integration and its underlying neural basis are rare. In fish, an explosive escape behavior known as C-start is driven by an identified neural circuit centered on the Mauthner cell. The Mauthner cell can trigger C-starts in response to visual and auditory stimuli allowing to investigate how multisensory integration in a single neuron affects behavioral outcome after threat detection. Here we demonstrate that in goldfish visual looms and brief auditory stimuli can be integrated to increase C-start probability and that this enhancement is inversely correlated to the saliency of the cues with weaker auditory cues producing a proportionally stronger multisensory effect. We also show that multisensory stimuli reduce response latency locked to the presentation of the auditory cue. Finally, we make a direct link between behavioral data and its underlying neural mechanism by reproducing empirical data with an integrate-and-fire computational model of the Mauthner cell.

Subcellular Dissection of a Simple Neural Circuit: Functional Domains of the Mauthner-Cell During Habituation

Sensorimotor integration is a pivotal feature of the nervous system for ensuring a coordinated motor response to external stimuli. In essence, such neural circuits can optimize behavioral performance based on the saliency of environmental cues. In zebrafish, habituation of the acoustic startle response (ASR) is a simple behavior integrated into the startle command neurons, called the Mauthner cells. Whereas the essential neuronal components that regulate the startle response have been identified, the principles of how this regulation is integrated at the subcellular regions of the Mauthner cell, which in turn modulate the performance of the behavior, is still not well understood. Here, we reveal mechanistically distinct dynamics of excitatory inputs converging onto the lateral dendrite (LD) and axon initial segment (AIS) of the Mauthner cell by in vivo imaging glutamate release using iGluSnFR, an ultrafast glutamate sensing fluorescent reporter. We find that modulation of glutamate release is dependent on NMDA receptor activity exclusively at the AIS, which is responsible for setting the sensitivity of the startle reflex and inducing a depression of synaptic activity during habituation. In contrast, glutamate-release at the LD is not regulated by NMDA receptors and serves as a baseline component of Mauthner cell activation. Finally, using in vivo calcium imaging at the feed-forward interneuron population component of the startle circuit, we reveal that these cells indeed play pivotal roles in both setting the startle threshold and habituation by modulating the AIS of the Mauthner cell. These results indicate that a command neuron may have several functionally distinct regions to regulate complex aspects of behavior.

Intersection of motor volumes predicts the outcome of ambush predation of larval zebrafish

ABSTRACTEscape maneuvers are key determinants of animal survival and are under intense selection pressure. A number of escape maneuver parameters contribute to survival, including response latency, escape speed and direction. However, the relative importance of these parameters is context dependent, suggesting that interactions between parameters and predatory context determine the likelihood of escape success. To better understand how escape maneuver parameters interact and contribute to survival, we analyzed the responses of larval zebrafish (Danio rerio) to the attacks of dragonfly nymphs (Sympetrum vicinum). We found that no single parameter explains the outcome. Instead, the relative intersection of the swept volume of the nymph's grasping organs with the volume containing all possible escape trajectories of the fish is the strongest predictor of escape success. In cases where the prey's motor volume exceeds that of the predator, the prey survives. By analyzing the intersection of these volumes, we compute the survival benefit of recruiting the Mauthner cell, a neuron in anamniotes devoted to producing escapes. We discuss how the intersection of motor volume approach provides a framework that unifies the influence of many escape maneuver parameters on the likelihood of survival.

Intersection of motor volumes predicts the outcome of ambush predation of larval zebrafish

The escape maneuvers of animals are key determinants of their survival. Consequently these maneuvers are under intense selection pressure. Current work indicates that a number of escape maneuver parameters contribute to survival including response latency, escape speed, and direction. This work has found that the relative importance of these parameters is context dependent, suggesting that interactions between escape maneuver parameters and the predatory context together determine the likelihood of escape success. However, it is unclear how escape maneuver parameters interact to contribute to escape success across different predatory contexts. To clarify these issues, we investigated the determinants of successful escape maneuvers by analyzing the responses of larval zebrafish to the attacks of dragonfly nymphs. We found that the strongest predictor of the outcome was the time needed for the nymph to reach the fish’s initial position at the onset of the attack, measured from the time that the fish initiates its escape response. We show how this result is related to the intersection of the swept volume of the nymph’s grasping organs with the volume containing all possible escape trajectories of the fish. By analyzing the intersection of these volumes, we compute the survival benefit of recruiting the Mauthner cell, a neuron in anamniotes devoted to producing escapes. We discuss how escape maneuver parameters interact in determining escape response. The intersection of motor volume approach provides a framework that unifies the influence of many escape maneuver parameters on the likelihood of survival.

The Mauthner Cell Microcircuits: Sensory Integration, Decision-Making, and Motor Functions

The teleost and amphibian Mauthner (M) cell is the critical decision-making element in a brainstem microcircuit that decides whether unimodal or multimodal stimuli are sufficiently threatening to the animal’s survival to warrant a massive motor response. This behavior, called the startle response or C-start, was initially characterized as a reflex, when in fact its governing process involves computations that can occur over a period as short as a few milliseconds or as long as 0.5 s. Because much of what is known about this system was derived from studies in goldfish of the C-start evoked by loud, abrupt sounds and from the associated basic electrophysiology, this behavior is discussed first. Then the chapter addresses M-cell-initiated escapes triggered by more complex stimuli and the notion that the behavior can be voluntary. Finally, it describes insights from studying the M-cell system that provide a model for the construction of brainstem decision-making microcircuits.