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

Transient and sustained effects of dopamine and serotonin signaling in motivation‐related behavior

“…Another study showed that the activation of axons in VTA from DR caused sustained reinforcement effects and the release of dopamine in the NAc, suggesting that although serotonin neurons mediate signaling for reinforcement, serotonin may not cause sustained effects directly at the projection sites for reinforcing behavior. Other studies have not observed the reinforcement effects of serotonin neurons following stimulation in the soma . Therefore, sustained effects of serotonin are evident in specific contexts, such as reversal learning and social conditioning.…”

“…During engaging in the task, serotonin stimulation did not affect motor behavior for approaching to cues . However, in another behavioral context of free‐moving in the open field, stimulation of serotonin neurons in the DR inhibited spontaneous locomotion acutely within 1 s and the termination of stimulation recovered locomotion within 4 s, suggesting that serotonin inhibited locomotion behavior transiently . Interestingly, suppression of locomotion was not observed when mice engaged in tasks such as rotarod or reward‐approaching tasks, suggesting that serotonin indirectly modulates factors that drive behaviors .…”

“…53 However, in another behavioral context of free-moving in the open field, stimulation of serotonin neurons in the DR inhibited spontaneous locomotion acutely within 1 s and the termination of stimulation recovered locomotion within 4 s, suggesting that serotonin inhibited locomotion behavior transiently. 39 Interestingly, suppression of locomotion was not observed when mice engaged in tasks such as rotarod or reward-approaching tasks, suggesting that serotonin indirectly modulates factors that drive behaviors. 39 Although the studies above reported transient effects of serotonin activation that apparently suppressed some aspects of behaviors, a separate study revealed that when PFC inputs onto the DR were stimulated with optogenetics, which are supposed to activate the DR, mice exhibited increases in effort-related behavior during the forced-swim test.…”

Hippocampal oscillatory dynamics and sleep atonia are altered in an animal model of fibromyalgia: Implications in the search for biomarkers

“…In light of these and other related experiments, Jacobs and Fornal suggested that the serotonergic system is especially involved in facilitating the motor output involved in central pattern generators, and in relation to the behavioral state (Lydic & Baghdoyan, ). In accordance with this hypothesis, the optogenetic stimulation of serotonergic neurons in the DRN modulates certain motor activity types (Correia et al, ).…”

The Long and the Short of Serotonergic Stimulation: Optogenetic activation of dorsal raphe serotonergic neurons changes the learning rate for rewards

“…Despite theoret- 37 ical suggestions for an association with aversive learning [19,53,13,6,15], direct 38 experimental tests into serotonin's role in RL tasks have led to a complex pattern of 39 results [12,52,42,45,22,11]. For instance, recent optogenetic studies reporting that 40 stimulating 5-HT neurons could lead to positive reinforcement [42] do not appear to 41 be consistent with other optogenetic findings, which instead suggest an involvement 42 with patience [22,45] and even locomotion [11]. 43 Here, we study a different aspect of the involvement of 5-HT in RL.…”