Principles of presynaptic networks for single layer 2/3 neurons in ferret visual cortex Single neurons in neocortical circuits are driven by presynaptic networks composed of excitatory and inhibitory neurons. Each neuron’s population of presynaptic partners determines how incoming information is processed. A longstanding view of cortical circuits is that a majority of synaptic inputs originate from local networks through horizontal (recurrent) connections. However, the mechanisms by which recurrent networks shape the activity of cortical neurons is largely unknown. Additionally, synaptic and cellular mechanisms proposed by theoretical models rely on studies of the rodent visual cortex, which is increasingly shown to differ from that of carnivores and primates in organization and function. The proposed career development plan aims to address these problems by mapping presynaptic excitatory and inhibitory cells of single layer 2/3 neurons and dissecting how they act to selectively modulate neural activity in ferret V1 in vivo. This proposal uses a novel combination of advanced optical techniques and electrophysiology. The candidate has a deep background in in vivo physiology and optical imaging in a wide variety of mammalian species. The candidate proposes to receive training in state-of- the-art multiphoton holographic optogenetics and the use of novel molecular tools. The candidate will also receive guidance from mentors and advisors on professional development. This training will establish the necessary skills for a successful independent research career studying the role of presynaptic networks in fundamental cortical operations in a non-murine model system. The candidate will carry out the mentored phased under Dr. David Fitzpatrick, a world-prominent expert on the early visual-system and cortical processing of carnivores and primates. The candidate will be co-mentored by Dr. Hillel Adesnik, who is a pioneer in multiphoton holographic optogenetics and developed techniques the candidate proposes to use. Additional advising from Dr. Kristina Nielsen and Dr. Krishnan Padmanabhan will provide guidance in professional development and the transition to an academic position. MPFI will provide an excellent research environment, with abundant resources, technical support, and intellectual discussions with prominent scientists to help ensure successful completion of the proposed research and transition to independence. The candidate’s long-term aspirations are to build an innovative and multidisciplinary research program to establish fundamental principles of cortical circuits, ultimately providing a scaffold for understanding disorders, such as schizophrenia and autism, which show profound impairments in the processing of sensory signals.