A04

In animals, value based decision-making depends on prior experience and current internal state. Which neurons take part in this type of decision-making, their coding principles, and neural network properties are not well understood. An important network component encoding and signaling value in the brain are dopaminergic neurons (DANs). In the mammalian brain, dopaminergic neurons can be found in many brain areas including the ventral tegmental area, the prefrontal cortex, the substantia nigra, and the olfactory bulb. Only some of these types of DANs have been implicated in reward or decision-making. Furthermore, dopamine has been most well studied in the context of memory and reinforcement learning. Recent studies in the fly including our work of the last funding periods (Bracker et al., 2013; Lewis et al., 2015; Siju et al., 2014) have, however, argued that dopamine has more immediate modulatory effects on behavior in a context-dependent manner (Cohn et al., 2015; Owald et al., 2015). These studies suggest that DANs in the fly’s higher brain centers integrate current internal state and external information acutely to modulate sensory processing and ultimately behavior. How value is represented in populations of DANs and how internal state (e.g., hunger) and experience are integrated in this representation needs further investigation and remained an open question from our previous work.
The aim of this project is to unravel the modulatory role of DANs in olfactory processing in two different model systems (fly mushroom body (MB), mouse olfactory bulb (OB)). To this end, we are adapting an in vivo volumetric imaging and automated unbiased image analysis method to map the response to different stimuli (i.e. positive, negative, neutral odors, sugar) within the DAN network. This will allow us to analyze whether DANs have hard-wired or plastic representations of value that differ or not, across individuals and/or change in an internal state and/or experience-dependent manner. In the fly, by taking advantage of the genetic toolset, we will analyze DAN responses at the microcircuit level (synaptic interaction among different DANs and other neurons of the MB circuit) and behavioral level. In the mouse, we will profit from an interaction with Jovica Ninkovic in the network, who is interested in neurogenesis and network integration of newly generated DANs in the mouse OB. Little is known, at this point, about the function of the large number of DANs in the OB. We have recently setup in vivo OB imaging in the lab with the help of members of the network. Using specific cre recombinase expressing transgenic mouse lines to label DANs with Ca2+ indicators (GCaMP), we will image DAN responses to odors and relate them to odor valence and internal state of the animal. Together, this project will elucidate how DANs encode value and how state-dependent representation impacts on olfactory processing and ultimately modulate animal decision-making and behavior.