Serotonin (5-HT) is associated with mood and motivation but the function of endogenous 5-HT remains controversial. Here, we studied the impact of phasic optogenetic activation of 5-HT neurons in mice over time scales from seconds to weeks. We found that activating dorsal raphe nucleus (DRN) 5-HT neurons induced a strong suppression of spontaneous locomotor behavior in the open field with rapid kinetics (onset ≤1 s). Inhibition of locomotion was independent of measures of anxiety or motor impairment and could be overcome by strong motivational drive. Repetitive place-contingent pairing of activation caused neither place preference nor aversion. However, repeated 15 min daily stimulation caused a persistent increase in spontaneous locomotion to emerge over three weeks. These results show that 5-HT transients have strong and opposing short and long-term effects on motor behavior that appear to arise from effects on the underlying factors that motivate actions.
Bibliographical noteFunding Information:
We thank members of the Systems Neuroscience Lab for many helpful discussions; Histology, Vivarium, Glass Wash and Media Preparation, Optical Imaging and Microscopy platforms, Enrica Audero, Margarida Duarte, Ana Nunes and João Cruz for technical assistance; Gonçalo Lopes and Niccolò Bonacchi for help with Bonsai software; Catherine French and Costa Lab for the accelerating rotarod; Gil Costa for support with visual diagrams and Champalimaud Research for the fruitful collaborative environment. This work was supported by Fundação para a Ciência e Tecnologia (fellowship SFRH/BD/33277/2007 to PAC; SFRH/BD/51210/2010 to ASM), Human Frontier Science Program (fellowship LT000881/2011L to EL), Howard Hughes Medical Institute (International Early Career Scientist to MRC), European Research Council (Advanced Investigator Grants 250334 and 671251 to ZFM; Start- ing Investigator Grant 640093 to MRC), and the Champalimaud Foundation (ZFM).
© Correia et al.