The influence of serotonergic signaling on visual and visuomotor cortical processing

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Visual perception and its coupling to motor processes are often important for precise motor behavior. Perception and motor action can be influenced during certain emotional states, such as motivation, anger, fear, or attention. Serotonin has been identified as a main transmitter involved in emotional modulation and acts in particular on G protein coupled receptors (GPCRs). Serotonergic projections are known to innervate early primary sensory and motor cortical areas. However, the effects of serotonin on activity dynamics in visual and motor cortex are unknown. Furthermore, visual areas closely interact with cortical motor output activities but these widespread inter-areal interactions are currently poorly understood. In this grant we will investigate the influence of serotonergic transmitter release and intracellular signaling on visual and visuomotor cortical processing and we will determine which serotonergic signaling pathways are involved. We will further test in how far serotonergic input modulates local intra-areal processing vs. modulation of inter-areal interactions. We will therefore apply optogenetic tools for the control of serotonin release and the down-stream signals in anaesthetized as well as awake and behaving (here head-fixed) mice. Additionally, we will perform single-cell recordings in brain slices of the manipulated brain networks to accomplish our investigations at different levels of network complexity. To capture the network activity patterns within and across multiple brain areas we will exploit wide-field optical imaging using voltage- and Ca2+-sensitive fluorescent sensors, which allows recording of population activity at the required high spatial and temporal resolutions. We will use our tools to monitor cortical activity during visual tasks in the context of precise control of serotonergic signals. Using visually-guided motor activity, i.e. a simple walking task combined with visual flow-field input, we will test how serotonin modulates motor behavior and how such processes are encoded in visual and motor cortical network activity patterns. The experiments shall lead to a better understanding of the modulation of visual processing under influence of serotonin and its importance for movement adjustment. In order to perform these demanding experiments we would like to jointly combine our expertise in optogenetics and in in vivo animal recordings in the applied project.