Cooperative Agreements

 DESCRIPTION (provided by applicant): One of the biggest challenges in neuroscience is to understand how neural circuits in the brain process, encode, store, and retrieve information. Meeting this challenge will require methods to record the activity of intact neural networks in freely behaving animals. Spectacular advances with the development of genetically encoded indicators of neural activity and optogenetic actuators now call for methods to image and manipulate the activity of large populations of identified neurons in freely moving mice over prolonged periods of time.

 DESCRIPTION (provided by applicant): Despite the growing availability of optical markers of neuronal activity, as well as genetic tools for optical manipulation, current optical microscopy techniques for imaging the intact brain at cellular resolution have approached their limits, particularly in terms of 3D volumetric imaging speeds. The brain and nervous system is inherently 3D, with cortical layers playing specific roles in information processing.

DESCRIPTION (provided by applicant): A major goal in neuroscience is to understand the computations performed by local brain circuits. A large obstacle to achieving this goal is that - at least in mammals - we currently cannot observe the spiking activity of most neurons within a circuit. A key reason is that standard electrodes are just too big, and provoke too much damage to brain tissue. If placed with high enough density to sample a majority of neurons, they would destroy the very circuit they are intended to monitor.

 DESCRIPTION (provided by applicant): The brain is a massively interconnected network of regions, each of which contains neural circuits that process information related to combinations of sensory, motor and internal variables. Adaptive behavior requires that these regions communicate: sensory and internal information must be evaluated and used to make a decision, which must then be transformed into a motor output.

 DESCRIPTION (provided by applicant): Brain Machine Interfaces (BMIs) allow the nervous system to directly communicate with external devices in order to mitigate deficits associated with neurodegeneration or to drive peripheral prosthetics.

 DESCRIPTION (provided by applicant): The purpose of this RFA is to promote the integration of experimental, analytic and theoretical capabilities for the examination of neural circuits and systems. This proposal is highly responsive to the RFA in that it links several different neuroscience labs to develop new technologies that provide for simultaneous multistate imaging and applies these technologies to the examination of how neuronal dynamics in mammalian cortex varies as a function of brain state and development.

 DESCRIPTION (provided by applicant): High resolution deep tissue calcium imaging with large field of view wavefront correction Two-photon microscopy based calcium imaging allows in vivo observation of neuronal dynamics at high spatial and temporal resolutions. The latest development allows single action potential sensitivity and single dendritic spine resolution, which provides a powerful solution to investigate the function of neural circuits. However, such resolution and sensitivity can only be achieved for the upper ~400 µm of neocortex of adult mice.

 DESCRIPTION (provided by applicant): The system that controls smooth pursuit eye movements is one of the most accessible, promising systems for understanding how neural circuits transform sensory inputs into actions. Pursuit is a natural, ecologically- relevant behavir that allows primates to track moving objects of interest in the visual world.

 DESCRIPTION (provided by applicant): To address the core question underlying the Obama Brain Initiative to better understand the function of complex brain circuits, we propose a multi-scale recording and data analysis project to study the dynamical interactions between sensory cortex, motor cortex, and the basal ganglia in the process of motor planning and execution. The multi-scale approach will involve simultaneous recordings at the cellular, network, and systems level in head-fixed behaving mice trained to perform a rewarded locomotor task.

 DESCRIPTION (provided by applicant): The anatomical substrates and cellular mechanisms underlying reward-dependent learning have been studied for decades, but the specific circuit and network interactions between the cortex, striatum, and midbrain that mediate action selection have not been systematically investigated. Here, we bring together three different investigators with specialized expertise in each of these three brain regions.