Transient inhibition and long-term facilitation of locomotion by phasic optogenetic activation of serotonin neurons

Abstract

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.

DOI: http://dx.doi.org/10.7554/eLife.20975.001

eLife digest

The brain controls sleep, movement and the other behaviors that an animal needs to survive. A chemical called serotonin plays an important role in controlling these behaviors as it regulates the activity of nerve cells (known as neurons) throughout the brain. Serotonin is produced by a specific group of neurons found in an area at the base of the brain called the raphe nuclei. From there, serotonin is released into other parts of the brain to influence different behaviors. Although drugs that target serotonin are widely used as antidepressants, how this chemical signal acts in the brain remains a mystery. This is due, in part, to it being technically challenging to carry out experiments on the serotonin-producing neurons.

A technique called optogenetics uses light to selectively activate or inhibit individual cells in live animals. Here, Correia, Lottem et al. use optogenetics to activate serotonin-producing neurons in the dorsal raphe nucleus of mice. The experiments show that triggering serotonin production for a few seconds causes the mice to move around more slowly as they explore their surroundings. This short-term release of serotonin only slows the mice down if they are not already occupied with other activities, such as finding water or balancing on a moving object. These experiments suggest that serotonin decreases an individual’s motivation to move but that this can be overcome by sufficiently powerful goals. In contrast, repeatedly activating the serotonin neurons over a period of several weeks led to long-term changes of the opposite kind – the mice begin to move around more quickly.

The findings of Correia, Lottem et al. have possible implications for the use of drugs that target serotonin to treat mental disorders as it suggests important links between serotonin, movement, and the ability of the brain to change how it responds to certain situations. The next steps will be to investigate how the two different effects of serotonin are connected, which areas in the brain are involved and how best to apply these findings to clinical studies.

DOI: http://dx.doi.org/10.7554/eLife.20975.002