Award Abstract # 1707408
NeuroNex Technology Hub: Miniaturized open source devices for calcium imaging, electrophysiology, and real-time control of neural activity

NSF Org: DBI
Division of Biological Infrastructure
Recipient: UNIVERSITY OF CALIFORNIA, LOS ANGELES
Initial Amendment Date: July 31, 2017
Latest Amendment Date: July 22, 2022
Award Number: 1707408
Award Instrument: Cooperative Agreement
Program Manager: Sridhar Raghavachari
sraghava@nsf.gov
 (703)292-4845
DBI
 Division of Biological Infrastructure
BIO
 Directorate for Biological Sciences
Start Date: October 1, 2017
End Date: September 30, 2023 (Estimated)
Total Intended Award Amount: $3,660,000.00
Total Awarded Amount to Date: $9,582,530.00
Funds Obligated to Date: FY 2017 = $1,830,000.00
FY 2018 = $1,830,000.00

FY 2019 = $2,262,530.00

FY 2020 = $1,830,000.00

FY 2021 = $1,830,000.00
History of Investigator:
  • Peyman Golshani (Principal Investigator)
    PGolshani@mednet.ucla.edu
  • Jason Cong (Co-Principal Investigator)
  • Alcino Silva (Co-Principal Investigator)
  • Hugh Blair (Co-Principal Investigator)
  • Sotiris Masmanidis (Co-Principal Investigator)
Recipient Sponsored Research Office: University of California-Los Angeles
10889 WILSHIRE BLVD STE 700
LOS ANGELES
CA  US  90024-4200
(310)794-0102
Sponsor Congressional District: 36
Primary Place of Performance: University of California-Los Angeles
710 Westwood Plaza
Los Angeles
CA  US  90095-7334
Primary Place of Performance
Congressional District:
36
Unique Entity Identifier (UEI): RN64EPNH8JC6
Parent UEI:
NSF Program(s): Cross-BIO Activities
Primary Program Source: 01001718DB NSF RESEARCH & RELATED ACTIVIT
01001819DB NSF RESEARCH & RELATED ACTIVIT

01001920DB NSF RESEARCH & RELATED ACTIVIT

01002021DB NSF RESEARCH & RELATED ACTIVIT

01002122DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 1228, 8091, 9178, 9179
Program Element Code(s): 727500
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.074

ABSTRACT

To understand how the brain processes information, creates and retrieves memories, and makes decisions it is necessary to record the activity of thousands of brain cells simultaneously. New small and light-weight microscopes have been developed that can be carried on the heads of laboratory mice and rats. These microscopes take advantage of new probes that sense calcium levels and flash bright when a brain cell becomes active. The Neuronex Neurotechnology Hub has built new miniature microscopes that not only sense light but can also directly record the electrical activity of the large numbers of cells deep in the brain. This combination of electrical and optical recordings gives scientists the new ability to read out how large groups of brain cells and brain regions work together as the brain senses, learns, plans and executes actions. The Neuronex Neurotechnology Hub will also create new computer systems that can analyze these activity patterns extremely quickly (within small fractions of a second). This rapid feedback system will allow investigators to rapidly probe how the activity of specific groups of brain cells is linked to each behavior. Finally, the Hub will build and test a new miniature microscope called a "light field miniature microscope". This version of the microscope will allow investigators to make 3-D movies of brain activity, greatly improving their view of the large network of brain cells. All these technologies will be openly shared with neuroscience community through a website (miniscope.org), such that each laboratory can build each of these devices themselves at very low cost. The Hub will hold workshops to teach scientists how to build and use the various devices. Finally the hub will reach out to the broader community by holding classes for K-12 and college students, and demonstrating how these devices can give us a view of brain function.

This Neurotechnology Hub will develop and share next-generation miniaturized in vivo sensing devices that integrate optical and electrophysiological recording from hundreds or thousands of neurons in behaving animals. These devices will be coupled with energy-efficient computing hardware for real-time signal processing and closed-loop feedback capabilities. The Hub will also create light field miniaturized microscopes that will allow three dimensional optical recordings of network activity in freely behaving animals. Last, the Hub will manufacture and distribute custom made, 3 dimensional silicon microprobes for large scale electrophysiological recordings. Making these devices widely available for neuroscience research and teaching will have significant broader impacts, by accelerating discovery and broadening outreach. The devices and techniques will be distributed widely to a large community of researchers, as previously done with the open-source miniaturized microscope developed by the PIs (the website at miniscope.org already has >2500 registered users and >250 labs using our microscope), as well as with silicon microprobes (>100 devices have been shared with users). Hence, the Hub will have a broad impact upon neuroscience research, facilitating many future advances in our understanding of the neural basis for emotion, cognition, and behavior, with a high potential to catalyze major new discoveries. The PIs will establish an outreach program through partnership with the Minority Access to Research Careers program at UCLA, as well as the UCLA Center for Excellence in Engineering and Diversity (CEED), to involve highly diversified high school and undergraduate students in this research. This NeuroTechnology Hub award is funded by the Division of Emerging Frontiers within the Directorate for Biological Sciences as part of the BRAIN Initiative and NSF's Understanding the Brain activities.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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(Showing: 1 - 10 of 15)
Chen, Zhe and Blair, Garrett J. and Blair, Hugh T. and Cong, Jason "Fast Calcium Trace Extraction for Large-Field-of-View Miniscope" IEEE Biomedical Circuits and Systems Conference (BioCAS), , 2021 https://doi.org/10.1109/BioCAS49922.2021.9644936 Citation Details
Chen, Zhe and Blair, Garrett J. and Guo, Changliang and Aharoni, Daniel and Blair, Hugh T. and Cong, Jason Cong "Live Demonstration: Real-Time Calcium Trace Extraction from Large-Field-of-View Miniscope" The 2021 IEEE Biomedical Circuits and Systems Conference (BioCAS) , 2021 https://doi.org/10.1109/BioCAS49922.2021.9645015 Citation Details
Chen, Zhe and Blair, Hugh T. and Cong, Jason "Energy-Efficient LSTM Inference Accelerator for Real-Time Causal Prediction" ACM Transactions on Design Automation of Electronic Systems , v.27 , 2022 https://doi.org/10.1145/3495006 Citation Details
Lazaro, Maria T. and Taxidis, Jiannis and Shuman, Tristan and Bachmutsky, Iris and Ikrar, Taruna and Santos, Rommel and Marcello, G. Mark and Mylavarapu, Apoorva and Chandra, Swasty and Foreman, Allison and Goli, Rachna and Tran, Duy and Sharma, Nikhil an "Reduced Prefrontal Synaptic Connectivity and Disturbed Oscillatory Population Dynamics in the CNTNAP2 Model of Autism" Cell Reports , v.27 , 2019 10.1016/j.celrep.2019.05.006 Citation Details
Lee, Kwang and Bakhurin, Konstantin I. and Claar, Leslie D. and Holley, Sandra M. and Chong, Natalie C. and Cepeda, Carlos and Levine, Michael S. and Masmanidis, Sotiris C. "Gain Modulation by Corticostriatal and Thalamostriatal Input Signals during Reward-Conditioned Behavior" Cell Reports , v.29 , 2019 10.1016/j.celrep.2019.10.060 Citation Details
Lee, Kwang and Claar, Leslie D. and Hachisuka, Ayaka and Bakhurin, Konstantin I. and Nguyen, Jacquelyn and Trott, Jeremy M. and Gill, Jay L. and Masmanidis, Sotiris C. "Temporally restricted dopaminergic control of reward-conditioned movements" Nature Neuroscience , v.23 , 2020 10.1038/s41593-019-0567-0 Citation Details
Lee, Kwang and Masmanidis, Sotiris C. "Aberrant features of in vivo striatal dynamics in Parkinson's disease" Journal of Neuroscience Research , v.97 , 2019 https://doi.org/10.1002/jnr.24519 Citation Details
Li, Bingzhao and Lee, Kwang and Masmanidis, Sotiris C and Li, Mo "A nanofabricated optoelectronic probe for manipulating and recording neural dynamics" Journal of Neural Engineering , v.15 , 2018 10.1088/1741-2552/aabc94 Citation Details
Nagai, Jun and Rajbhandari, Abha K. and Gangwani, Mohitkumar R. and Hachisuka, Ayaka and Coppola, Giovanni and Masmanidis, Sotiris C. and Fanselow, Michael S. and Khakh, Baljit S. "Hyperactivity with Disrupted Attention by Activation of an Astrocyte Synaptogenic Cue" Cell , v.177 , 2019 10.1016/j.cell.2019.03.019 Citation Details
Shuman, Tristan and Aharoni, Daniel and Cai, Denise J. and Lee, Christopher R. and Chavlis, Spyridon and Page-Harley, Lucia and Vetere, Lauren M. and Feng, Yu and Yang, Chen Yi and Mollinedo-Gajate, Irene and Chen, Lingxuan and Pennington, Zachary T. and "Breakdown of spatial coding and interneuron synchronization in epileptic mice" Nature Neuroscience , v.23 , 2020 10.1038/s41593-019-0559-0 Citation Details
Skocek, Oliver and Nöbauer, Tobias and Weilguny, Lukas and Martínez Traub, Francisca and Xia, Chuying Naomi and Molodtsov, Maxim I. and Grama, Abhinav and Yamagata, Masahito and Aharoni, Daniel and Cox, David D. and Golshani, Peyman and Vaziri, Alipasha "High-speed volumetric imaging of neuronal activity in freely moving rodents" Nature Methods , v.15 , 2018 10.1038/s41592-018-0008-0 Citation Details
(Showing: 1 - 10 of 15)

PROJECT OUTCOMES REPORT

Disclaimer

This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.

Our NSF NeuroNex Center was highly successful and met all of the goals outlined in the grant proposal. The Center had 4 main goals: 1. To design, build, and test an integrated miniaturized microscopy and electrophysiology device (named the E-Scope) for simultaneous electrical recordings and calcium imaging through the same device. 2. To design, build and test an FPGA-based device for real-time analysis of miniaturized calcium imaging data. 3. To build and distribute electrophysiological multi-electrode silicon probes to the neuroscience community. 4. To build a light-field miniaturized microscope for volumetric calcium imaging in freely moving mice.

1.     We have designed, built and tested the E-scope. The device can perform simultaneous calcium imaging and multi-electrode electrophysiological recordings, with all the data and power delivered through a single co-axial wire. We implanted silicon probe for electrophysiological recordings in cerebellum and placed the lens of miniaturized microscope in the anterior cingulate cortex for calcium imaging. We were able to perform simultaneous imaging and electrophysiology in animals socially interacting with other animals and compared this to interactions with an object. We discovered neurons modulated by social interactions in the cerebellum which may underlie how this region regulates social interactions. This work was published in E-Life.

2.     We built the FPGA-based device for calcium imaging in freely behaving animals. We tested this device on hippocampal CA1 activity patterns that encode the location of the animal in space. We were able to determine the location of the animals by reading out the activity of CA1 neurons in real-time, setting the foundations for future experiments where the device could potentially be used a brain-machine interface. This work was published in E-Life.

3.     We built 1500 multielectrode silicon probes and shared them with over 50 laboratories world-wide.

4.     We designed, built and tested a light-field miniaturized microscope for volumetric imaging of activity in freely moving mice. This work was published in the Nature Methods.

We have shared almost all this technology with the neuroscience community in an open-source manner. Our miniaturized microscopes are being used by more 800 laboratories world-wide.

 


Last Modified: 10/03/2023
Modified by: Peyman Golshani

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