NINscope, a versatile miniscope for multi-region circuit investigations

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Abstract

Miniaturized fluorescence microscopes (miniscopes) have been instrumental to monitor neural signals during unrestrained behavior and their open-source versions have made them affordable. Often, the footprint and weight of open-source miniscopes is sacrificed for added functionality. Here, we present NINscope: a light-weight miniscope with a small footprint that integrates a high-sensitivity image sensor, an inertial measurement unit and an LED driver for an external optogenetic probe. We use it to perform the first concurrent cellular resolution recordings from cerebellum and cerebral cortex in unrestrained mice, demonstrate its optogenetic stimulation capabilities to examine cerebello-cerebral or cortico-striatal connectivity, and replicate findings of action encoding in dorsal striatum. In combination with cross-platform acquisition and control software, our miniscope is a versatile addition to the expanding tool chest of open-source miniscopes that will increase access to multi-region circuit investigations during unrestrained behavior.

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Fully integrated silicon probes for high-density recording of neural activity

Matteo Carandini, James Jun, Nicholas Steinmetz … (2017)

Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution, but from only a few dozen neurons per shank. Optical Ca2+ imaging offers more coverage but lacks the temporal resolution needed to distinguish individual spikes reliably and does not measure local field potentials. Until now, no technology compatible with use in unrestrained animals has combined high spatiotemporal resolution with large volume coverage. Here we design, fabricate and test a new silicon probe known as Neuropixels to meet this need. Each probe has 384 recording channels that can programmably address 960 complementary metal–oxide–semiconductor (CMOS) processing-compatible low-impedance TiN sites that tile a single 10-mm long, 70 × 20-μm cross-section shank. The 6 × 9-mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed and digitized on the base, allowing the direct transmission of noise-free digital data from the probe. The combination of dense recording sites and high channel count yielded well-isolated spiking activity from hundreds of neurons per probe implanted in mice and rats. Using two probes, more than 700 well-isolated single neurons were recorded simultaneously from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed large populations of neurons from several brain structures to be recorded in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens a path towards recording of brain-wide neural activity during behaviour.

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A shared neural ensemble links distinct contextual memories encoded close in time

Denise Cai, Daniel Aharoni, Tristan Shuman … (2016)

Recent studies suggest the hypothesis that a shared neural ensemble may link distinct memories encoded close in time 1–13 . According to the memory allocation hypothesis 1,2 , learning triggers a temporary increase in neuronal excitability 14–16 that biases the representation of a subsequent memory to the neuronal ensemble encoding the first memory, such that recall of one memory increases the likelihood of recalling the other memory. Accordingly, we report that the overlap between the hippocampal CA1 ensembles activated by two distinct contexts acquired within a day is higher than when they are separated by a week. Multiple convergent findings indicate that this overlap of neuronal ensembles links two contextual memories. First, fear paired with one context is transferred to a neutral context when the two are acquired within a day but not across a week. Second, the first memory strengthens the second memory within a day but not across a week. Older mice, known to have lower CA1 excitability 16,17 , do not show the overlap between ensembles, the transfer of fear between contexts, or the strengthening of the second memory. Finally, in aged animals, increasing cellular excitability and activating a common ensemble of CA1 neurons during two distinct context exposures rescued the deficit in linking memories. Taken together, these findings demonstrate that contextual memories encoded close in time are linked by directing storage into overlapping ensembles. Alteration of these processes by aging could affect the temporal structure of memories, thus impairing efficient recall of related information.

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Efficient and accurate extraction of in vivo calcium signals from microendoscopic video data

Pengcheng Zhou, Shanna Resendez, Jose Rodriguez-Romaguera … (2018)

In vivo calcium imaging through microendoscopic lenses enables imaging of previously inaccessible neuronal populations deep within the brains of freely moving animals. However, it is computationally challenging to extract single-neuronal activity from microendoscopic data, because of the very large background fluctuations and high spatial overlaps intrinsic to this recording modality. Here, we describe a new constrained matrix factorization approach to accurately separate the background and then demix and denoise the neuronal signals of interest. We compared the proposed method against previous independent components analysis and constrained nonnegative matrix factorization approaches. On both simulated and experimental data recorded from mice, our method substantially improved the quality of extracted cellular signals and detected more well-isolated neural signals, especially in noisy data regimes. These advances can in turn significantly enhance the statistical power of downstream analyses, and ultimately improve scientific conclusions derived from microendoscopic data.

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Author and article information

Contributors

Chris I De Zeeuw:

ORCID: https://orcid.org/0000-0001-5628-8187

Tycho M Hoogland:

ORCID: https://orcid.org/0000-0002-7444-9279

Megan R Carey: Role: Reviewing Editor

Kate M Wassum: Role: Senior Editor

Journal

Journal ID (nlm-ta): eLife

Journal ID (iso-abbrev): Elife

Journal ID (publisher-id): eLife

Title: eLife

Publisher: eLife Sciences Publications, Ltd

ISSN (Electronic): 2050-084X

Publication date (Electronic, pub): 14 January 2020

Publication date Collection: 2020

Volume: 9

Electronic Location Identifier: e49987

Affiliations

[1 ]deptNetherlands Institute for Neuroscience Royal Netherlands Academy of Arts and Sciences AmsterdamNetherlands

[2 ]deptDepartment of Psychiatry Amsterdam UMC, University of Amsterdam AmsterdamNetherlands

[3 ]deptFaculty of Applied Sciences TU Delft DelftNetherlands

[4 ]deptDepartment of Neuroscience Erasmus MC RotterdamNetherlands

Champalimaud Foundation Portugal

University of California, Los Angeles United States

Champalimaud Foundation Portugal

Mount Sinai School of Medicine United States

Author information

Bastijn JG van den Boom http://orcid.org/0000-0002-0853-3763

Mario Negrello https://orcid.org/0000-0002-8527-4259

Ingo Willuhn http://orcid.org/0000-0001-6540-6894

Chris I De Zeeuw https://orcid.org/0000-0001-5628-8187

Tycho M Hoogland https://orcid.org/0000-0002-7444-9279

Article

Publisher ID: 49987

DOI: 10.7554/eLife.49987

PMC ID: 6989121

PubMed ID: 31934857

SO-VID: 6f6b0c4e-adcd-4494-ab75-310634d83eac

License:

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

History

Date received : 10 July 2019

Date accepted : 13 January 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001722, Koninklijke Nederlandse Akademie van Wetenschappen;

Award ID: 240-840100

Award Recipient : Chris I De Zeeuw Tycho M Hoogland

Funded by: FundRef http://dx.doi.org/10.13039/100010663, H2020 European Research Council;

Award ID: ERC-2014-STG 638013

Award Recipient : Ingo Willuhn

Funded by: FundRef http://dx.doi.org/10.13039/501100003246, Nederlandse Organisatie voor Wetenschappelijk Onderzoek;

Award ID: 2015/06367/ALW 864.14.010

Award Recipient : Ingo Willuhn

Funded by: FundRef http://dx.doi.org/10.13039/501100003246, Nederlandse Organisatie voor Wetenschappelijk Onderzoek;

Award ID: ALWOP.2015.076

Award Recipient : Chris I De Zeeuw Tycho M Hoogland

Funded by: FundRef http://dx.doi.org/10.13039/100010663, H2020 European Research Council;

Award ID: ERC-adv ERC-POC

Award Recipient : Chris I De Zeeuw

Funded by: Topsector Life Sciences & Health (LSH);

Award ID: LSHM18001

Award Recipient : Tycho M Hoogland

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Custom metadata

Author impact statement A light-weight, compact and open-source miniaturized fluorescence microscope integrates dual region brain imaging, optogenetic stimulation and behavioral parsing using an accelerometer.

ScienceOpen disciplines: Life sciences

Keywords: miniscope,cerebellum,cerebral cortex,striatum,mouse,imaging

Data availability:

ScienceOpen disciplines: Life sciences

Keywords: miniscope, cerebellum, cerebral cortex, striatum, mouse, imaging

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NINscope, a versatile miniscope for multi-region circuit investigations

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Most cited references 50

Fully integrated silicon probes for high-density recording of neural activity

A shared neural ensemble links distinct contextual memories encoded close in time

Efficient and accurate extraction of in vivo calcium signals from microendoscopic video data

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Cited by 45

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