The mammalian visual system utilizes a powerful set of algorithms to extract crucial information from the environment that informs an individual's decisions. These algorithms require constant adjustment to match the individual's current needs ? a task achieved partly by neuromodulators such as serotonin. In some cases, these modulatory systems open the door for maladaptive changes to visual processing. For example, visual hallucination is a debilitating yet common neurological symptom arising in many distinct disorders, including schizophrenia and Parkinson's disease. Serotonin receptors are key mediators of these symptoms, and their blockade by antipsychotics disrupts hallucinations. However, these drugs cause numerous unwanted side effects, and the lack of therapies with greater specificity reflects the gaps in our understanding of exactly how serotonergic signaling modulates visual processing. Our fundamental goal is to understand the circuit mechanisms underlying serotonergic modulation of visual processing to better inform models of visual function and therapeutic targeting of visual hallucinations. In this proposal, we use genetic tools in mouse visual cortex to determine how visual cortical computations are affected by serotonergic modulation. In our first aim, we will measure the effects of serotonin 5HT2A receptor activation on spontaneous and visually evoked activity, followed by identification and manipulation of specific cortical cell types. In our second aim, we will determine how contextual information from outside the classic receptive field is integrated, based on the computation of normalization, and modulated by these receptors. Together these experiments will reveal the role of serotonergic signaling in processing of both local and global information, which should in turn provide insight into disorders of altered perception such as schizophrenia.
Disruptions in serotonergic signaling are implicated in disorders such as schizophrenia that are also marked by hallucinations and disrupted sensory perception. This proposal combines powerful techniques that will allow for previously unprecedented resolution into the mechanisms of serotonergic modulation of visual cortical processing. Revealing these mechanisms will not only advance our understanding of how the brain processes visual information, but also offers promise for discovering new ways to ameliorate the devastating effects of disrupted perception in afflicted individuals.
