Physiological responses of mechanosensory systems in the head of larval zebrafish (Danio rerio).

The lateral line system of zebrafish consists of the anterior lateral line, with neuromasts distributed on the head, and the posterior lateral line, with neuromasts distributed on the trunk. The sensory afferent neurons are contained in the anterior and posterior lateral line ganglia, respectively. So far, the vast majority of physiological and developmental studies have focused on the posterior lateral line. However, studies that focus on the anterior lateral line, especially on its physiology, are very rare. The anterior lateral line involves different neuromast patterning processes, specific distribution of synapses, and a unique role in behavior. Here, we report our observations regarding the development of the lateral line and analyze the physiological responses of the anterior lateral line to mechanical and water jet stimuli. Sensing in the fish head may be crucial to avoid obstacles, catch prey, and orient in water current, especially in the absence of visual cues. Alongside the lateral line, the trigeminal system, with its fine nerve endings innervating the skin, could contribute to perceiving mechanosensory stimulation. Therefore, we compare the physiological responses of the lateral line afferent neurons to responses of trigeminal neurons and responsiveness of auditory neurons. We show that anterior lateral line neurons are tuned to the velocity of mechanosensory ramp stimulation, while trigeminal neurons either only respond to mechanical step stimuli or fast ramp and step stimuli. Auditory neurons did not respond to mechanical or water jet stimuli. These results may prove to be essential in designing underwater robots and artificial lateral lines, with respect to the spectra of stimuli that the different mechanosensory systems in the larval head are tuned to, and underline the importance and functionality of the anterior lateral line system in the larval fish head.

Sarm1 is dispensable for mechanosensory-motor transformations in zebrafish.

Sarm1 is an evolutionary conserved protein that is essential for Wallerian axon degeneration. Sarm1 has emerged as a therapeutic target to treat neuropathies derived from metabolic or chemical stress and physical injury of axons. Yet, the full repertoire of consequences of inhibiting Sarm1 remains unknown. Here we show that loss of Sarm1 in zebrafish does not affect the sensorimotor transformations that underlie rheotaxis. In addition, Sarm1 deficit accelerates the re-growth of regenerating axons. These data indicate that systemic inhibition of Sarm1 is a viable therapeutic option compatible with sustained nervous system function.

Behavior, Electrophysiology, and Robotics Experiments to Study Lateral Line Sensing in Fishes.

The lateral line system is a sensory system unique to fishes and amphibians. It is composed of distributed mechanosensory hair cell organs on the head and body (neuromasts), which are sensitive to pressure gradients and water movements. Over the last decade, we have pursued an interdisciplinary approach by combining behavioral, electrophysiology, and robotics experiments to study this fascinating sensory system. In behavioral and electrophysiology experiments, we have studied the larval lateral line system in the model genetic organism, zebrafish (Danio rerio). We found that the lateral line system, even in 5-day-old larvae, is involved in an array of behaviors that are critical to survival, and the deflection of a single neuromast can elicit a swimming response. In robotics experiments, we used a range of physical models with distributed pressure sensors to better understand the hydrodynamic environments from the local perspective of a fish or robot. So far, our efforts have focused on extracting control-related information for a range of application scenarios including characterizing unsteady flows such as Kármán vortex streets for station holding. We also used robot models to test biological hypotheses on how morphology and movement of fishes affect lateral line sensing. Overall, with this review we aim to increase the visibility and accessibility of this multi-disciplinary research approach.

Projections of the Diencephalospinal Dopaminergic System to Peripheral Sense Organs in Larval Zebrafish (Danio rerio).

Dopaminergic neurons of the descending diencephalospinal system are located in the posterior tuberculum (PT) in zebrafish (Danio rerio), and correspond in mammals to the A11 group in hypothalamus and thalamus. In the larval zebrafish, they are likely the only source of central dopaminergic projections to the periphery. Here, we characterized posterior tubercular dopaminergic fibers projecting to peripheral sense organs, with a focus on the lateral line neuromasts. We labeled and identified catecholaminergic neurons and their projections by combining two immunofluorescence techniques, (i) using an antibody against Tyrosine hydroxylase, and (ii) using an antibody against GFP in transgenic zebrafish expressing in catecholaminergic neurons either membrane-anchored GFP to track fibers, or a Synaptophysin-GFP fusion to visualize putative synapses. We applied the CLARITY method to 6 days old whole zebrafish larvae to stain and analyze dopaminergic projections by confocal microscopy. We found that all lateral line neuromasts receive direct innervation by posterior tubercular dopaminergic neurons, and tracked these projections in detail. In addition, we found dopaminergic fibers projecting to the anterior and posterior lateral line ganglia, and extensive central dopaminergic arborizations around the terminal projection field of the lateral line afferent neurons in the hindbrain medial octavolateralis nucleus (MON). Therefore, dopaminergic innervation may affect lateral line sense information at different processing stages. Additional dopaminergic fibers innervate the trigeminal ganglion, and we observed fine catecholaminergic fibers in the skin with arborization patterns similar to free sensory nerve endings. We also detected potentially dopaminergic fibers innervating inner ear sensory epithelia. Therefore, the diencephalospinal A11-type dopaminergic system may broadly modulate peripheral senses. We also briefly report peripheral sympathetic catecholaminergic projections labeled in our experiments, and their innervation of the developing intestine, swim bladder and abdominal organs.

Afferent and motoneuron activity in response to single neuromast stimulation in the posterior lateral line of larval zebrafish.

The lateral line system of fishes contains mechanosensory receptors along the body surface called neuromasts, which can detect water motion relative to the body. The ability to sense flow informs many behaviors, such as schooling, predator avoidance, and rheotaxis. Here, we developed a new approach to stimulate individual neuromasts while either recording primary sensory afferent neuron activity or swimming motoneuron activity in larval zebrafish (Danio rerio). Our results allowed us to characterize the transfer functions between a controlled lateral line stimulus, its representation by primary sensory neurons, and its subsequent behavioral output. When we deflected the cupula of a neuromast with a ramp command, we found that the connected afferent neuron exhibited an adapting response which was proportional in strength to deflection velocity. The maximum spike rate of afferent neurons increased sigmoidally with deflection velocity, with a linear range between 0.1 and 1.0 µm/ms. However, spike rate did not change when the cupula was deflected below 8 µm, regardless of deflection velocity. Our findings also reveal an unexpected sensitivity in the larval lateral line system: stimulation of a single neuromast could elicit a swimming response which increased in reliability with increasing deflection velocities. At high deflection velocities, we observed that lateral line evoked swimming has intermediate values of burst frequency and duty cycle that fall between electrically evoked and spontaneous swimming. An understanding of the sensory capabilities of a single neuromast will help to build a better picture of how stimuli are encoded at the systems level and ultimately translated into behavior.