Dopaminergic Modulation of Mechanosensory Circuits

• Applicant: Professor Dr. Johann Heinrich Bollmann, since 1/2023
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 446150760

Our senses detect stimuli from the environment, and after processing by the nervous system, allow us to respond appropriately. Mechanosensation is among the earliest and most fundamental forms of stimulus reception. It includes the detection of touch stimuli, noxious stimuli and water motion, for example via free nerve endings in the skin which sense mechanical, thermal and noxious stimuli in vertebrates.Depending on behavioral states, the sensitivity of sensory neurons can be modified. For example, sensation is down-regulated during sleep or increased during arousal. Inhibition of sensory systems can occur during self-induced stimulation. Further, sensitivity of nociceptive cells increases after injury or is suppressed temporarily during fight. Long-term modifications in pain processing can occur due to sustained pain perception and lead to chronic pain. In our model, the larval zebrafish (Danio rerio), mechanical stimuli are sensed by free nerve endings in the skin and by specialized mechanosensory hair cells in the lateral line system, which detect water motion. Both sensory systems likely receive direct modulatory efferent input from a group of dopaminergic cells in the diencephalon. These far-projecting diencephalic dopaminergic neurons are homologous to the hypothalamic A11 dopaminergic neurons in mammals. The A11 neurons have been implicated in modulating sensory pathways and to play a role in diseases, that involve sensory abnormalities like Restless Legs Syndrome, Chronic Pain and Migraine.Although recent studies have indicated that the A11-type dopaminergic neurons play an important role in modulating sensory systems and are involved in several neuropathies the exact mechanisms of this modulation and details of the circuitry are not well understood.Here we investigate the circuitry between A11 homologous dopaminergic neurons and the mechanosensory organs in larval zebrafish using optophysiological and electrophysiological techniques, with the aim to understand the biological function of this dopaminergic modulation of sensory systems. Larval zebrafish are an excellent model to study circuit function, due to their small size, almost complete transparency and susceptibility to transgenic tools, which allows physiological experiments in intact and behaving animals. The results of this investigation may help us to understand the function of dopaminergic modulation of the mechanosensory systems in vertebrates and to establish a model for dopaminergic modulatory regulation of mechanosensory and possibly nociceptive circuits.

• DFG Programme: Research Grants
• Ehemalige Antragstellerin: Dr. Melanie Hähnel-Taguchi, until 1/2023