Modulation of brain activity and sensory computations by habenula-dorsal raphe circuitry

Our emotional states have significant impact in the way we perceive our world. For example, our reaction to the loud sound of fireworks can be extremely different if we are having a relaxed evening with family, or if we are anxious right after a traffic accident. This strong modulation of neural processing is crucial for making correct decisions in different circumstances by evaluating both our internal emotional states and the environmental cues. Any dysfunction in these processes can lead to mood disorders ranging from anxiety to depressive or manic behaviours. Despite the common occurrence of mood disorders in society, it is not clear what neural mechanisms underlie how our emotional states affects the way we perceive our world. The main goal of this project is to understand how emotional states regulates brain activity and connectivity and how these alterations, in turn, modify sensory information processing in the vertebrate brain. During this first period, we established a series of behavioral assays that allows us to measure and quantify animals? emotional states with a focus on foraging and defensive behaviors. Our preliminary results show that genetic perturbation of habenula and raphe has a direct impact on these behaviors. Moreover, we established imaging strategies, which now allows us to monitor brain activity of animals with genetically perturbed habenula and raphe. Our preliminary results show genetic perturbation of raphe and habenula alters the synchrony of forebrain neurons. We are currently analyzing these data sets for further insights into these alterations. Finally, we also developed a genetic strategy, where we can genetically identify different components of habenula and raphe, while imaging the rest of neural populations. We expect that furthering these experiments will allow us to investigate the relationship between specific habenula and raphe neurons with the rest of the forebrain neurons. Due to COVID19 situation, the hiring and the entrance for several of our new lab members to Norway is delayed significantly. This delayed the start of some of our experiments. Luckily the technician who is working on the project is very experienced. This well trained technician already collected several promising data sets, and now training new lab members to contribute to this project.

Our internal state constantly modulates the way we perceive our world. For example, our reaction to the sound of fireworks can be very different if we are having a relaxed evening, or right after a traffic accident. Such modulation of sensory computations is essential for making correct decisions by evaluating the environmental cues within the context of our internal state. Indeed, this process is critical for survival as it help us recognize what is important and initiate appropriate behaviors. Any dysfunction in these processes can lead to a variety of mood disorders. Yet, it is not clear what neural mechanisms underlie how our internal state affects the way we perceive our world. One major brain circuitry important for regulating internal states in various context is the habenula-dorsal raphe circuitry. Habenula and dorsal raphe are evolutionarily conserved brain regions that play important roles in learning, prediction of outcomes, aversion/attraction and sleep. However, the precise role of this circuitry in modulating brain activity and sensory computations is yet to be understood. In this proposal we will determine the role of habenula-dorsal raphe circuitry in modulating brain activity, sensory computations and animal behavior. To achieve this goal: 1) We will investigate the impact of specific perturbations of habenula-dorsal raphe circuitry in sensory induced behaviors. 2) We will determine how opto-/chemogenetic perturbations of habenula-dorsal raphe circuitry modulate the activity, the functional connectivity and the sensory responses of the entire forebrain circuits of awake/behaving juvenile zebrafish. The habenula-dorsal raphe circuitry is known to be associated with several neuropsychological conditions, such as mood disorders and addiction in humans. Our results will reveal the neural computations underlying the role of this network in modulating the sensory responses.