NINscope, a versatile miniscope for multi-region circuit investigations
- Netherlands Institute for Neuroscience, Netherlands
- TU Delft, Netherlands
- Erasmus Medical Center, Netherlands
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
Bastijn JG van den Boom
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.
Reviewing Editor
- Megan R Carey, Champalimaud Foundation, Portugal
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.
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.
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NINscope, a versatile miniscope for multi-region circuit investigations
eLife 9:e49987.
https://doi.org/10.7554/eLife.49987
Further reading
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- Neuroscience
Parkinson’s disease (PD) is characterized by motor impairments caused by degeneration of dopamine neurons in the substantia nigra pars compacta. In addition to these symptoms, PD patients often suffer from non-motor comorbidities including sleep and psychiatric disturbances, which are thought to depend on concomitant alterations of serotonergic and noradrenergic transmission. A primary locus of serotonergic neurons is the dorsal raphe nucleus (DRN), providing brain-wide serotonergic input. Here, we identified electrophysiological and morphological parameters to classify serotonergic and dopaminergic neurons in the murine DRN under control conditions and in a PD model, following striatal injection of the catecholamine toxin, 6-hydroxydopamine (6-OHDA). Electrical and morphological properties of both neuronal populations were altered by 6-OHDA. In serotonergic neurons, most changes were reversed when 6-OHDA was injected in combination with desipramine, a noradrenaline (NA) reuptake inhibitor, protecting the noradrenergic terminals. Our results show that the depletion of both NA and dopamine in the 6-OHDA mouse model causes changes in the DRN neural circuitry.
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- Neuroscience
A key to motor control is the motor thalamus, where several inputs converge. One excitatory input originates from layer 5 of primary motor cortex (M1L5), while another arises from the deep cerebellar nuclei (Cb). M1L5 terminals distribute throughout the motor thalamus and overlap with GABAergic inputs from the basal ganglia output nuclei, the internal segment of the globus pallidus (GPi), and substantia nigra pars reticulata (SNr). In contrast, it is thought that Cb and basal ganglia inputs are segregated. Therefore, we hypothesized that one potential function of the GABAergic inputs from basal ganglia is to selectively inhibit, or gate, excitatory signals from M1L5 in the motor thalamus. Here, we tested this possibility and determined the circuit organization of mouse (both sexes) motor thalamus using an optogenetic strategy in acute slices. First, we demonstrated the presence of a feedforward transthalamic pathway from M1L5 through motor thalamus. Importantly, we discovered that GABAergic inputs from the GPi and SNr converge onto single motor thalamic cells with excitatory synapses from M1L5. Separately, we also demonstrate that, perhaps unexpectedly, GABAergic GPi and SNr inputs converge with those from the Cb. We interpret these results to indicate that a role of the basal ganglia is to gate the thalamic transmission of M1L5 and Cb information to cortex.
