- How does the nervous system encode and process sensory information?
- What role does the modulation of sensory circuits play in adapting to different situations?
- How does sensory information transform into behavior?
We are studying these questions in the zebrafish model system. A five-day-old zebrafish larva already has a rich repertoire of behaviors that enable this small organism to avoid predators and survive. It uses visual, auditory and somatosensory cues, as well as information from the water motion, which it receives through the lateral line system, a unique sensory organ of fishes and aquatic amphibians. The receptors of the lateral line are mechanosensory hair cells, similar to those found in the auditory and vestibular system. Therefore, the study of the lateral line can provide insight into the general function of hair cell systems. The sensory circuitry of the lateral line receives neuromodulatory input at multiple levels. Neuromodulation can modify sensitivity and gain of a sensory circuit in the context of input from other sensory modalities, motor activity, or behavior.
Figure 2: Electrophysiological recordings of larval zebrafish neurons
(A) Spontaneous activity of lateral line afferent neuron recorded in loose-patch configuration in the posterior lateral line ganglion.
(B) Spontaneous activity of lateral line afferent neuron recorded in whole cell-path configuration in the posterior lateral line ganglion.
(C) “Fictive swimming” activity of motor neurons in response to a computer controlled water jet directed towards the lateral line neuromasts, recorded extracellularly from the ventral motor root.
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Figure1: The lateral line sensory Organ.
(A) Schematic of a 5-day-old zebrafish larva with neuromasts of the different branches of the lateral line depicted in different colors. TG: trigeminal ganglion, AG: anterior lateral line ganglion, PG: posterior lateral line ganglion.
(B) A neuromast can be stimulated with a water jet ejected from a micropipette, driven by a computer-controlled pump.
An important neuromodulator in the central nervous system is Dopamine. In zebrafish, a group of dopaminergic neurons in the diencephalon that corresponds to the A11 cluster in mammals, projects to multiple sensory systems at various levels and into the spinal cord. Also in the mammalian system, the A11 dopaminergic neurons are the only group that send descending projections into the spinal cord. They assume an important role in sensory modulation and abnormal dopamine signaling in these neurons plays a role in chronic pain and stands in connection to a common neurological disorder, the Restless Legs Syndrome (RLS), in which patients experience unpleasant sensation, mainly in the legs during rest.
Work from the Driever lab has shown that the far projecting diencephalic dopaminergic groups in the zebrafish depend on the transcription factor orthopeadia, and therefore correspond to the far projecting A11 neurons in mammals. It appears, due to their prominent innervation of the lateral line circuitry, and considering a recent study from the Driever lab (Reinig et al., 2017) which showed that activity in zebrafish A11-type neurons correlates with stimulation of the lateral line and the trigeminal system, this dopaminergic group is involved in the modulation of sensory processing in the zebrafish larva.
We are studying the zebrafish larval sensory circuits and their modulation using a combination of electrophysiology, imaging and behavioral experiments. Because of its small size and transparency, this model is ideally suited to conduct neurophysiological studies, and offers the opportunity to express fluorescent and calcium sensitive dyes in neuronal populations. The availability of many individuals of free-swimming, readily behaving larva also allows us to compare neurophysiological data to behavioral responses in free-swimming larvae with intact and perturbed dopaminergic signaling.