The brains of mammals contain an extraordinarily large number of neurons whose activity and interconnections determine the function of circuits that monitor our sensory environment, dictate our motor choices, form memories, and guide all behavior. However we do not understand how the activity of these circuits governs brain activity. A fundamental limitation has been the inability to monitor and control the activity of a significan fraction of brain cells at any one time - thus typical studies of the neural underpinnings of behavior monitor at most ~100 cells simultaneously, or approximately one millionth of the total. In order to gain insight how circuit computations are carried out and subsequently control behavior, we will develop two novel technologies. The first is a radical new class of electrode with 50-100 times more recording sites than is typical and with on-board electronics, allowing unprecedented quality recordings of high number of neurons. The second is a novel way to deliver light into the brain in a controlled manner in order to be able to perturb the activity of neurons with high precision.

Public Health Relevance

We will develop and implement novel technologies to record from and manipulate neurons in the brain of behaving mammals. We will develop novel active electrodes with 1000's of contact sites to increase the sampling of neurons in active circuits as well as tapered optical fibers with optical ports to perform optogenetic manipulations of select groups of neurons.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01NS094190-03
Application #
9331757
Study Section
Special Emphasis Panel (ZNS1)
Program Officer
Langhals, Nick B
Project Start
2015-09-30
Project End
2019-08-31
Budget Start
2017-09-01
Budget End
2019-08-31
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Harvard Medical School
Department
Biology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Sileo, Leonardo; Bitzenhofer, Sebastian H; Spagnolo, Barbara et al. (2018) Tapered Fibers Combined With a Multi-Electrode Array for Optogenetics in Mouse Medial Prefrontal Cortex. Front Neurosci 12:771
Angotzi, Gian Nicola; Malerba, Mario; Boi, Fabio et al. (2018) A Synchronous Neural Recording Platform for Multiple High-Resolution CMOS Probes and Passive Electrode Arrays. IEEE Trans Biomed Circuits Syst 12:532-542
Pisanello, Marco; Pisano, Filippo; Sileo, Leonardo et al. (2018) Tailoring light delivery for optogenetics by modal demultiplexing in tapered optical fibers. Sci Rep 8:4467
Markowitz, Jeffrey E; Gillis, Winthrop F; Beron, Celia C et al. (2018) The Striatum Organizes 3D Behavior via Moment-to-Moment Action Selection. Cell 174:44-58.e17
Jackman, Skyler L; Chen, Christopher H; Chettih, Selmaan N et al. (2018) Silk Fibroin Films Facilitate Single-Step Targeted Expression of Optogenetic Proteins. Cell Rep 22:3351-3361
Pisanello, Ferruccio; Mandelbaum, Gil; Pisanello, Marco et al. (2017) Dynamic illumination of spatially restricted or large brain volumes via a single tapered optical fiber. Nat Neurosci 20:1180-1188