Dissecting distinct contributions of different Prefrontal subregions on goal-directed visual attention

Visual attention is our ability to prioritize vision as a sensory modality, and our ability to extract discrete information from a visual scene. The prefrontal cortex (PFC) is considered a source of feedback modulation to the visual cortex– guiding, biasing or modulating activity in the visual cortex, to produce visual attention. The visual cortex of the mouse receives monosynaptic input from two discrete PFC subregions, the anterior cingulate cortex (ACA) and the orbitofrontal cortex (ORB), that contribute to diverse aspects of cognition. However, it is currently unknown how these distinct PFC subregions contribute to different aspects of visual attention. Equipped with precise understanding of distinct forms of PFC feedback modulation on visual processing, we will be in a better position to strategically intervene in disorders of visual processing and attention. The proposed work therefore aims to bridge the long-standing hypothesis of PFC feedback modulation with changes in population activity in the visual cortex, how this activity change alters visual processing, and ultimately what effect this has on goal-directed visual attention. To achieve this goal, I will quantitively and qualitatively compare the activity of ACA and ORB axons in the visual cortex during different behavioral epochs of visual attention (Aim 1), probing each areas contribution to different aspects of vision. In following, perturbating the activity of each discrete PFC output pathway, allows me to observe changes in population activity in the visual cortex, how this activity change alters visual processing, and ultimately what effect this has on goal-directed visual attention (Aim 2). Finally, I will target PFC output pathways with a distinct connectivity profile, to understand how these projections modulate the activity of the visual cortex, and if they represent a distinct functional module in regulating sensory processing (Aim 3). Understanding how discrete subregions of the PFC influence the activity of the visual cortex, and its behavioral consequences, will provide key insights towards the cellular underpinnings of visual processing in the brain. The proposed work will be conducted at the Brain and Cognitive Sciences Department, MIT, with the direct mentorship of Prof. Mriganka Sur (MIT), from which I have already benefitted experimental training in numerous techniques including two-photon microscopy, visual cortex neurophysiology, circuit anatomy, and behavior. In addition, I will receive training and guidance on optogenetic tools in combination with two-photon imaging, and PFC physiology from Prof. Ofer Yizhar (WI), and computational methods in population activity analysis from Prof. Mehrdad Jazayeri (MIT). The outlined research, training, and mentorship will facilitate my long-term goal of establishing an independent researcher leveraging cutting-edge optical technologies available in mice to understand how PFC feedback modulation optimizes goal-directed sensory processing in the cortex.