Central to a current widespread effort to understand the neural underpinnings of behavior is the aim to visualize the real-time activity, and interactio between, populations of neurons in the awake, behaving animal. This effort has been recently been embraced by the NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative, which aims to accelerate the development and application of innovative technologies...to produce a revolutionary new dynamic picture of the brain that, for the first time shows how individual cells and complex neural circuits interact in both time and space. This S10 proposal brings together five NIH funded investigators whose aim is to generate these kinds of brain activity maps to understand the neuronal circuits that underlie anxiety, cognition, motivation and motor control. Here, we outline the use of 2-photon microscopy in vivo to map the functional circuits that underlie behavior. In this proposal, we have focused on two systems for deep brain functional calcium imaging, the hippocampus and the basal ganglia. The team includes Dr. Rene Hen, who aims to image adult neuronal stem cells and their progeny in the dentate gyrus to determine their contribution to mood and cognition. Dr. Joshua Gordon will image the prefrontal cortex and its inputs from the ventral hippocampus and amygdala to understand how these structures interact to control emotional behavior. Dr. Mazen Kheirbek will image the dorsal and ventral dentate gyrus to understand their relative contribution to contextual learning and emotional control. Dr. David Sulzer will use novel fluorescent false neurotransmitters to directly measure calcium and neurotransmitter release and reuptake in the same synapse in vivo during sensory and motor behaviors. Dr. Christoph Kellendonk will measure the activity in direct and indirect pathway medium spiny neurons of the striatum to understand how the balance of activity patterns in these neurons impact motivational state. The use of in vivo 2-photon microscopy described in this proposal will allow for unprecedented access to the circuits that underlie emotional behavior, motivational control and basic motor function. Use of this instrument will produce novel and before unattainable insight into the circuits that underlie neuropsychiatric illnesses, including anxiety/depression, schizophrenia, substance abuse and movement disorders such as Parkinson's disease.
