NINscope, a versatile miniscope for multi-region circuit investigations
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 control software, our miniscope is a versatile addition to the expanding toolbox of open-source miniscopes that will increase access to multi-region circuit investigations during unrestrained behavior.
Data availability
Hardware, firmware and software have been deposited at GitHub under an MIT license.
Article and author information
Author details
Funding
Koninklijke Nederlandse Akademie van Wetenschappen (240-840100)
- Chris I De Zeeuw
- Tycho M Hoogland
Topsector Life Sciences & Health (LSHM18001)
- Tycho M Hoogland
H2020 European Research Council (ERC-2014-STG 638013)
- Ingo Willuhn
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (2015/06367/ALW 864.14.010)
- Ingo Willuhn
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (ALWOP.2015.076)
- Chris I De Zeeuw
- Tycho M Hoogland
H2020 European Research Council (ERC-adv ERC-POC)
- Chris I De Zeeuw
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All performed experiments were licensed by the Dutch Competent Authority and approved by the local Animal Welfare Body, following the European guidelines for the care and use of laboratory animals Directive 2010/63/EU.
Reviewing Editor
- Megan R Carey, Champalimaud Foundation, Portugal
Version history
- Received: July 10, 2019
- Accepted: January 13, 2020
- Accepted Manuscript published: January 14, 2020 (version 1)
- Version of Record published: January 29, 2020 (version 2)
Copyright
© 2020, de Groot et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 9,375
- Page views
-
- 1,118
- Downloads
-
- 73
- Citations
Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
Perceptual decisions about sensory input are influenced by fluctuations in ongoing neural activity, most prominently driven by attention and neuromodulator systems. It is currently unknown if neuromodulator activity and attention differentially modulate perceptual decision-making and/or whether neuromodulatory systems in fact control attentional processes. To investigate the effects of two distinct neuromodulatory systems and spatial attention on perceptual decisions, we pharmacologically elevated cholinergic (through donepezil) and catecholaminergic (through atomoxetine) levels in humans performing a visuo-spatial attention task, while we measured electroencephalography (EEG). Both attention and catecholaminergic enhancement improved decision-making at the behavioral and algorithmic level, as reflected in increased perceptual sensitivity and the modulation of the drift rate parameter derived from drift diffusion modeling. Univariate analyses of EEG data time-locked to the attentional cue, the target stimulus, and the motor response further revealed that attention and catecholaminergic enhancement both modulated pre-stimulus cortical excitability, cue- and stimulus-evoked sensory activity, as well as parietal evidence accumulation signals. Interestingly, we observed both similar, unique, and interactive effects of attention and catecholaminergic neuromodulation on these behavioral, algorithmic, and neural markers of the decision-making process. Thereby, this study reveals an intricate relationship between attentional and catecholaminergic systems and advances our understanding about how these systems jointly shape various stages of perceptual decision-making.
-
- Neuroscience
The relationship between obesity and human brain structure is incompletely understood. Using diffusion-weighted MRI from ∼30,000 UK Biobank participants, we test the hypothesis that obesity (waist-to-hip ratio, WHR) is associated with regional differences in two micro-structural MRI metrics: isotropic volume fraction (ISOVF), an index of free water, and intra-cellular volume fraction (ICVF), an index of neurite density. We observed significant associations with obesity in two coupled but distinct brain systems: a prefrontal/temporal/striatal system associated with ISOVF and a medial temporal/occipital/striatal system associated with ICVF. The ISOVF~WHR system colocated with expression of genes enriched for innate immune functions, decreased glial density, and high mu opioid (MOR) and other neurotransmitter receptor density. Conversely, the ICVF~WHR system co-located with expression of genes enriched for G-protein coupled receptors and decreased density of MOR and other receptors. To test whether these distinct brain phenotypes might differ in terms of their underlying shared genetics or relationship to maps of the inflammatory marker C-reactive Protein (CRP), we estimated the genetic correlations between WHR and ISOVF (rg = 0.026, P = 0.36) and ICVF (rg = 0.112, P < 9×10−4) as well as comparing correlations between WHR maps and equivalent CRP maps for ISOVF and ICVF (P<0.05). These correlational results are consistent with a two-way mechanistic model whereby genetically determined differences in neurite density in the medial temporal system may contribute to obesity, whereas water content in the prefrontal system could reflect a consequence of obesity mediated by innate immune system activation.