Cooperative Agreements

TITLE kHz-rate in vivo imaging of neural activity throughout the living brain SUMMARY The overarching challenge in neuroscience today is how to monitor the neural signaling events in intact brains of behaving animals at synaptic or cellular spatial resolution and millisecond time resolution. Multiphoton fluorescence microscopy stands out among the existing brain imaging methods because of its ability to visualize the neuronal signals in optically opaque brains at sub-micron spatial resolution. However, hampered by the fundamental speed limitation of the gold-standard mechanical scanning mir

Project Summary/Abstract A major goal of the BRAIN Initiative is in creating new systems for being able to record and modulate neuronal activity across wide areas of cortex and at the scale of small ensembles and even individual neurons.

Project summary  Currently,  no  technology  exists  that  has  been  specifically  designed  to  allow  high  precision  noninvasive  neuromodulation and neuroimaging in awake animals. Ultrasound is an ideal modality to fill this void since it has  been  used  (1)  directly  for  neuromodulation,  (2)  for  functional  imaging  of  cerebral  blood  flow,&nbsp

High-throughput 3D random access three-photon structural and functional imaging Two-photon microscopy allows in vivo observation of neuronal dynamics at high spatial and temporal resolutions. The latest development of calcium indicators enables single action potential sensitivity and single dendritic spine resolution. However, such resolution and sensitivity is limited to the upper ~400 µm of the neocortex in adult mice. Most of the studies are still restricted within layer 2/3 neurons.

Summary Our goal is to develop a new class of electrophysiological recording devices, on the same physical scale as the neurons they record, by combining modern imaging with implanted optoelectronics. Although conventional multi-electrode recording can monitor neural activity with high temporal precision, it is chronically invasive due to the wires/shanks used to bring signals out. Optical imaging techniques, conversely, provide finer spatial resolution, easing neural identification, but at the cost of significantly worse temporal resolution.

PROJECT SUMMARY ABSTRACT Understanding how brains process information and how dysfunction disrupts that processing requires measuring patterns of neural activity with cellular spatial and millisecond temporal resolution. These patterns are by nature distributed: many brain regions contribute to any given act of perception, cognition, or action. Adding to this complexity is both neuronal diversity and plasticity: each region contains neurons of many different cell types, each with distinct physiology and anatomy, and neural activity patterns evolve throughout the lifespan.

Summary Neuroscience has an essential requirement for large-scale neural recording and perturbation technologies for the understanding of brain function, as well as in the diagnosis and treatment of neurological disorders. At present, a large gap exists between the localized optical microscopy studies looking at fast neuronal activities at single cell resolution level and the whole-brain observations of slow hemodynamics and brain metabolism provided by the macroscopic imaging modalities.

Abstract Recording the spiking activity of many individual neurons in a densely packed region of the brain has been a standing challenge for the neuroscience community. Recently developed in genetically encoded voltage indicators have sufficiently fast kinetics to record action potentials with millisecond temporal resolution from single neurons the brains of live model organisms. These sensors offer hope of large scale recordings of neuron spikes.

PROJECT SUMMARY/ABSTRACT Monitoring local concentrations of neurochemicals in specific parts of the brain in vivo is critical for correlating neural circuit functionality to behavior as long-range neuromodulation can significantly alter information processing. Current methods for detecting neuromodulators have limited temporal and/or spatial resolution, limited sensitivity and/or are prohibitively invasive.

Project Summary Oxygen levels (pO2) in the brain play a significant role in influencing the function of single neurons and neuronal networks during normal and pathological states. Mechanisms of such interactions between neuronal function and oxygen supply and consumption are not well understood relying largely on theoretical models and qualitative measurements. In addition, current and emerging neural implants disrupt the local blood-brain barrier as they penetrate the brain during placement potentially leading to oxidative stress in brain tissue along the path of the implant.