A Convergent and Essential Interneuron Pathway for Mauthner-Cell-Mediated Escapes

Abstract

The Mauthner cell (M-cell) is a command-like neuron in teleost fish whose firing in response to aversive stimuli is correlated with short-latency escapes [1-3]. M-cells have been proposed as evolutionary ancestors of startle response neurons of the mammalian reticular formation [4], and studies of this circuit have uncovered important principles in neurobiology that generalize to more complex vertebrate models [3]. The main excitatory input was thought to originate from multisensory afferents synapsing directly onto the M-cell dendrites [3]. Here, we describe an additional, convergent pathway that is essential for the M-cell-mediated startle behavior in larval zebrafish. It is composed of excitatory interneurons called spiral fiber neurons, which project to the M-cell axon hillock. By in vivo calcium imaging, we found that spiral fiber neurons are active in response to aversive stimuli capable of eliciting escapes. Like M-cell ablations, bilateral ablations of spiral fiber neurons largely eliminate short-latency escapes. Unilateral spiral fiber neuron ablations shift the directionality of escapes and indicate that spiral fiber neurons excite the M-cell in a lateralized manner. Their optogenetic activation increases the probability of short-latency escapes, supporting the notion that spiral fiber neurons help activate M-cell-mediated startle behavior. These results reveal that spiral fiber neurons are essential for the function of the M-cell in response to sensory cues and suggest that convergent excitatory inputs that differ in their input location and timing ensure reliable activation of the M-cell, a feedforward excitatory motif that may extend to other neural circuits

Neuromodulatory Regulation of Behavioral Individuality in Zebrafish

“…To do this, we generated zebrafish larvae expressing YFP-tagged ChR2 (Lacoste et al, 2015) specifically in the DRN neurons. In tg(tph2:Gal4ff; 14xUAS-E1b:hChR2(H134R)-EYFP) larvae, ChR2 expression was restricted to the DRN and did not include other serotonergic populations (Figure 7A).…”

Motor Behavior Mediated by Continuously Generated Dopaminergic Neurons in the Zebrafish Hypothalamus Recovers after Cell Ablation

“…To test the sufficiency of th2+ neurons for the initiation of swimming, we expressed Channelrhodopsin-2 (ChR2) in these cells by crossing Tg(UAS:ChR2-YFP) a144 [21] and Tg(th2:Gal-VP16) zd202 fish (Figure S1E) Expression of the ChR2-YFP fusion protein specifically in posterior recess neurons allowed us to examine their axon trajectory and targets using whole-brain confocal imaging (Figure 3J; Movie S3). We found that a majority of axons appear to terminate a short distance from the posterior recess, likely in the posterior tuberculum.…”

Neural circuits that drive startle behavior, with a focus on the Mauthner cells and spiral fiber neurons of fishes

“…However, they also report observations indicating that SFNs may synapse with other cells and that their role in the circuit could be more complex. LaCoste et al, (2015) also examined the spiral fiber neurons and their role in the startle circuit. In this study, neurogenetic activation and ablation techniques were used to test hypotheses of SFN function.…”

“…One possible explanation is that SFNs synapse with cells other than the M-cell and loss of those connections is also associated with the aberrant bending. Although no additional connections of the SFN axons were observed by LaCoste et al, (2015), assessing the full complement of processes and connections is challenging.…”