Abstract
Happiness is key for both mental and physical well-being. To further understand the brain mechanisms involved, we utilized the cataplexy that occurs in narcoleptic animal models as a quantitative behavioral measure because it is triggered by actions associated with happiness, such as laughter in humans and palatable foods in mice. Here we report that the rostral part of the nucleus accumbens (NAc) shell is strongly activated during the beginning of chocolate-induced cataplexy in orexin neuron-ablated mice. We made a local lesion in the NAc using ibotenic acid and observed the animals’ behavior. The number of cataplexy bouts was negatively correlated to the lesion size. We also examined the hedonic response to palatable food by measuring the number of tongue protrusions in response to presentation of honey, which was also found to be negatively correlated to the lesion size. Next, we used clozapine N-oxide to either activate or inactivate the NAc through viral DREADD expression. As expected, the number of cataplexy bouts increased with activation and decreased with inactivation, and saline control injections showed no changes. Hedonic response in the DREADD experiment varied and showed both increases and decreases across mice. These results demonstrated that the rostral part of the NAc plays a crucial role in triggering cataplexy and hedonic orofacial movements. Since the NAc is also implicated in motivated behavior, we propose that the NAc is one of the key brain structures involved in happiness and is a driving force for positive emotion-related behaviors.
Highlights
Happiness is a key emotion for both mental and physical well-being
We included the areas reported to be related to cataplexy as revealed by c-Fos staining[6], but we focused on immediate activation of neurons rather than activation occurring over the course of hours by examining phosphorylated form of extracellular signal-regulated kinase (pERK) immunoreactivity
With a multiple comparison test, we found that activation of 4 brain regions were associated with the occurrence of cataplexy
Summary
Happiness is a key emotion for both mental and physical well-being. its benefits are well known, the underlying brain mechanisms are not well understood. One exception are the reports from the Berridge group that used facial expressions such as tongue protrusions for an animal model of happiness and “liking”[2]. The brain region responsible for cataplexy in orexin knockout mice, an animal model of narcolepsy[5], has already been reported to be the medial prefrontal cortex[6]. We examined a closer relationship between cataplexy and activated brain sites. We used another activation marker, the phosphorylated form of extracellular signal-regulated kinase (pERK), because it is induced more quickly and with a smaller time window than c-Fos[7,8]. We used adeno associated virus (AAV) as a vector to express hM3Dq-mCherry or hM4Di-mCherry under the control of calmodulin kinase IIα (CaMKIIα) promoter
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