Controlling the Serotonergic System in Mice by Light

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DESCRIPTION (provided by applicant): A major challenge to understand the relation between neural activity and development and ultimately between neuronal activity and behavior is to be able to control the activity of many nerve cells or regions of individual nerve cells simultaneously. Ideally, a technique for controlling nerve cell activity should be capable of switching nerve cells on or off within milliseconds without injuring the cells. We therefore will develop molecular light switches capable of controlling the membrane potential of cells. Light activated proton channels will be used to trigger depolarization, while either light activated potassium channels or Cl-transporters will be used to induce hyperpolarization. These constructs will first be tested in small neuronal nets from primary hippocampal neurons (introduced via viral infection) to better understand the cellular mechanisms underlying synaptic plasticity. Second, transgenic mice will be created, in which the molecular light switches will be under the control of a promoter specific for serotonergic neurons. Serotonin has been implicated in playing important roles in various physiological functions such as mood, sexual behavior, feeding, sleep/wake cycle, memory and cognition. Furthermore, changes in serotonin levels have been related to several diseases, e.g. depression, anxiety and schizophrenia. Understanding how serotonergic activity is modulating brain function will therefore be highly relevant for understanding behavior of mammals and will ultimately lead to the development of therapeutic approaches to cure dysfunctions of serotonergic transmission.