The dominant techniques for brain-wide functional imaging in humans and opaque mammals make use of he- modynamic contrast that results from coupling between neural activity and changes in blood flow and can be detected by noninvasive imaging methods including functional magnetic resonance imaging (fMRI), functional photoacoustic tomography (fPAT), functional ultrasound imaging (fUS), and others.
This is an application in response to RFA-NS-17-00 4 “BRAIN Initiative: Optimization of Transformative Technologies for Large Scale Recording and Modulation in the Nervous System (U01)”.
To understand how the brain computes, we need to understand how individual neurons in a circuit integrate their numerous inputs into output signals, as well as how they work together to encode a sensory input or execute a motor command in a behaving animal. Circuits and neurons are three-dimensional (3D) and can extend over hundreds or thousands of microns. Therefore, understanding their operations requires monitoring their activity at both synaptic and cellular resolution in 3D at image rates that capture all activity events. Behaving animals present a host of challenges to this goal.
In response to the BRAIN initiative RFA-NS-17-003 “New Technologies and Novel Approaches for Large-Scale Recording and Modulation in the Nervous System (U01)”, in this project we aim at accomplishing selective stimulation and recordings at ultra-high cellular level spatial resolution of distinct axonal b
One of the major challenges in neuroscience is to understand the experience-dependent mechanisms that drive the changes in neural circuits that underlie complex behaviors, and how these mechanisms are altered in disease. Altered synaptic transmission has been implicated in a number of human neurological and psychiatric disorders, including epilepsy, schizophrenia, autism and addiction.
Calcium signaling participates in almost every aspect of cell functioning, specifically in neurons. Genetically encoded calcium indicators (GECIs) developed from fluorescent proteins (FPs) provide a robust reliable readout of neuronal activity including spike number, timing, frequency, and levels of synaptic input.
A significant motivation of the BRAIN Initiative is the desire to understand information processing in neuronal tissues in situ.
This proposal presents an academic-industrial partnership to develop an instrument for 2-photon laser scanning microscopy (2p-LSM) in non-human primates (NHP) for transformative basic science and clinical translation. Our team combines academic strengths in neuroscience and neural engineering at New York University (PI Pesaran, co-I's Movshon and Peron) and industrial engineering at ThorLabs (led by Jeff Brooker, Vice-President of Life Sciences) to translate recent advances in 2p-LSM imaging by Karel Svoboda and his group at Janelia Research Campus to the monkey.
Neuromodulators are essential signaling molecules that regulate many neural processes, including cognition, mood, memory, and sleep, through their influence on brain circuits. Monitoring the release and distribution of neuromodulators in behaving animals is critical for understanding the diverse functions of these molecules. A major impediment to developing this understanding is the lack of tools that can monitor these compounds at the temporal, spatial and concentration scales relevant to these brain processes.
PROJECT SUMMARY Large scale manipulation of neural ensemble activity at cellular resolution and millisecond precision is a major technological goal of the BRAIN initiative.
