Repeated Social Defeat Affects Dopaminergic Modulation of Spinal Motor Circuits


Meeting Abstract

18-2  Saturday, Jan. 4 10:15 – 10:30  Repeated Social Defeat Affects Dopaminergic Modulation of Spinal Motor Circuits CLEMENTS, KN*; HEAGY, FK; BLAIN, E; WARD, J; ISSA, FA; East Carolina University, Greenville, NC clementsk10@students.ecu.edu

Social submission negatively impacts behavior and physiology of many social animals, yet the effects of repeated social defeat (RSD) on nervous system function underlying locomotion remain poorly understood. We investigated how RSD affects dopaminergic modulation of swimming and startle escape in zebrafish. Paired zebrafish form dominance relationships where subordinates are repeatedly defeated by their opponents. We showed that subordinates swim less and increase startle escape compared to dominants. Dopamine (DA) is involved in regulating locomotion by directly modulating spinal circuits. We studied whether DA signaling underlies this shift in locomotor activity. Western blot results showed that RSD decreases expression of dopamine 1 receptor (D1R). Pharmacological blockage of D1R caused dominants to swim less and escape more, resembling subordinate behavior. We also tested these behaviors in D1R knockout fish and found that they exhibited subordinate-like locomotive patterns. This suggests that RSD affects DA modulation of motor circuits by regulating the expression of D1R on postsynaptic targets. To test whether RSD also induces morphological changes within the presynaptic DA system, we counted the number of DA neurons in the hypothalamic A11 DA nuclei with Tg(dat:EGFP) zebrafish. The A11 nucleus is known to project into the spinal cord and modulate swim and escape circuits. Preliminary results of confocal images showed that RSD decreases total number of DA neurons in the A11. This suggests A11 is influenced by chronic defeat and allows exploration of if these neurons modulate the escape and swim circuits in the context of RSD. Our results highlight how RSD impacts CNS function and how this modifies adaptive motor behavior.

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