Title: Serotonergic Modulation of Orientation Tuning of Neurons in Primary Visual Cortex of Anesthetized Mice Running title: Serotonergic modulation of neurons in visual cortex

Introduction: Sensory processing is profoundly regulated by brain neuromodulatory systems. One of the main neuromodulators is serotonin which influences higher cognitive functions such as different aspects of perceptual processing. So, malfunction in the serotonergic system may lead to visual illusion in psychiatric disorders such as autism and schizophrenia. In this work, we examined the serotonergic modulation of visual responses of neurons to stimulus orientation in the primary visual cortex. Methods: Eight-weeks old naive mice were anesthetized and craniotomy was done on the region of interest in primary visual cortex. Spontaneous and visual-evoked activities of neurons were recorded before and during the electrical stimulation of dorsal raphe nucleus using in vivo whole-cell patch-clamp recording. Square-wave grating of 12 orientations was presented. Data was analyzed and Wilcoxon signed-rank test, used in order to compare the data of two conditions that belong to the same neurons, with or without electrical stimulation. Results: The serotonergic system changed orientation tuning of about 60 % recorded neurons by decreasing the mean firing rate in two independent visual response components: gain and baseline response. It also increased mean firing rate in a small number of neurons (about 20%). Beyond that, it left the preferred orientation and sensitivity of neurons unchanged. Conclusion: However, serotonergic modulation showed a bi-directional effect; it seems to cause predominately divisive and subtractive decreases in the visual responses of the neurons in the primary visual cortex that can modify the balance between internal and external sensory signals and result in disorders.