Research Projects

 DESCRIPTION (provided by applicant): Understanding how people think, act, and feel ultimately requires understanding how neural circuits interact spatially and temporally. This level of understanding requires fundamentally new tools that are high-throughput, direct, and non-invasive. Current methods are unable to satisfy all of these requirements simultaneously. An ideal tool would provide direct access to tens of thousands of individual neurons while not damaging the surrounding tissue.

 DESCRIPTION (provided by applicant): Multiphoton laser scanning microscopy has revolutionized neuroscience since it is less invasive than traditional electrophysiology methods for probing neuronal processes. In most cases, such imaging is limited to the observation of a single fluorescent species at modest depths (the depth penetration of standard 2-photon microscopy in brain tissue is limited a few 100s of microns). Recent proposals to extend this depth penetration have made use of 3-photon excitation.

 DESCRIPTION (provided by applicant): This application is in response to the President's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative.

 DESCRIPTION (provided by applicant): Electrophysiology and fluorescent imaging are widely used to study neural activity in vivo. These methods, however, require invasive procedures and can only sample small populations of neurons, and whole-brain fluorescent imaging of activity indicators is only able to capture a snapshot of the last state of the brain prior to euthanasia. W propose LOCATER: a transformative system that will transcend the limitations of these previous techniques.

 DESCRIPTION (provided by applicant): Neuropeptides are neuromodulators that regulate the physiology of cells, synapses, and neural circuits in the brain. For example, opioid neuropeptides are involved in pain and analgesia, and altered opioid neuropeptide levels have been observed in addiction, depression and anxiety, as well as a number of other neurological disorders including Parkinson's disease. Clearly, neuropeptides play a significant role in modulating behavior and cognition, but many aspects of neuropeptide signaling are not well understood.

 DESCRIPTION (provided by applicant): The goal of this proposal is to assess the feasibility of an all-molecular method for activity-dependent feedback control of neuronal activity. We propose to generate calcium sensitive light emitting molecules (bioluminescent enzymes, luciferases) that drive light sensing optogenetic elements (channels or ion pumps, opsins) to control membrane voltage at the level of single cells for positive and negative feedback control.

 DESCRIPTION (provided by applicant): A common metaphor to describe the brain is that it is like a supercomputer. Consequently, current efforts at improving technologies for large-scale recording of brain function are primarily focused on measuring its electrical activity. However, unlike a supercomputer, the brain is an electrochemical machine. Superimposed upon its network of synaptic connections is a "chemical connectome," a largely invisible network of neuromodulators, such as serotonin and neuropeptides (NPs), which exert a profound influence on brain function.

 DESCRIPTION (provided by applicant): A long-term goal of the BRAIN Initiative is to track activity in large numbers of neurons individually in behaving animals, thus capturing the information processing that is done by brain circuitry.

 DESCRIPTION (provided by applicant): An understanding of the neural mechanisms and computational principles of the human brain requires the study of non-human primates (NHP) in addition to small animals. NHP are the closest species to humans that can be readily studied invasively and have highly sophisticated perceptual, motor, and cognitive systems that share many similarities with our own.

 DESCRIPTION (provided by applicant): This