Cooperative Agreements

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.

Abstract The

ABSTRACT The neurotransmitter acetylcholine is widely distributed in the central nervous system and brain, and is a key signaling molecule involved in neural function. Current measurements of this important signaling molecule rely on implanted electrodes or sampling techniques, which often trade temporal or spatial resolution for chemical specificity, or vice versa.

The development of minimally invasive direct readouts of neural activity is one of the greatest challenges facing neuroscience today. Our laboratory is leading efforts to enable high resolution functional magnetic reso- nance imaging (fMRI) of molecular-level phenomena using MRI contrast agents sensitive to hallmarks of neu- ral activity. Calcium-sensitive fMRI is of outstanding interest.

Conditionally silencing the activity of specific neural ensembles is a powerful approach for mapping brain circuits responsible for specific behaviors. While microbial opsin- based tools exist to silence neural activity with light, these tools have significant limitations that make them unsuitable for persistent silencing over the course of minutes or hours.

Project Summary A longstanding goal in neuroscience is to understand the brain at the level of individual neurons. Existing techniques involve inserting electrodes that heavily damage the area that they are recording. Due to the damage it has also been very difficult to combine electrophysiology techniques with imaging the same neurons after the fact. We have developed novel carbon fiber electrode arrays, with individual elements that are 8 μm in diameter, smaller than most neuron cell bodies.

PROJECT SUMMARY Understanding how information is processed in the mammalian neocortex has been a longstanding question in neuroscience. While the action potential is the fundamental bit of information, how these spikes encode representations and drive behavior remains unclear. In order to adequately address this problem, it has become apparent that experiments are needed in which activity from large numbers of neurons can be measured in a detailed and comprehensive manner across multiple timescales. Direct measurements of action potentials have primarily been achieved by electrophysiology.

PROJECT SUMMARY This proposal aims to record and store neural activity into DNA/RNA strands with high spatial and temporal resolution, enabling neural activity recording densely within local circuits, yet broadly across large scale neural circuits, and potentially across the entire brain. Current technologies require tradeoffs in coverage, spatial resolution, or temporal resolution.