Simultaneous two-photon optogenetics and imaging of cortical circuits in three dimensions
Abstract
The simultaneously imaging and manipulating of neural activity in three-dimensions could enable the functional dissection of neural circuits. Here we have combined two-photon optogenetics with simultaneous volumetric two-photon calcium imaging to manipulate neural activity in mouse neocortex in vivo in 3D, while maintaining cellular resolution. Using a hybrid holographic approach, we simultaneously photostimulate more than 80 neurons over 150 μm in depth in cortical layer 2/3 from mouse visual cortex. We validate the usefulness of the microscope by photoactivating in 3D selected groups of interneurons, suppressing the response of nearby pyramidal neurons to visual stimuli. Our all-optical method could be used as a general platform to read and write activity of neural circuits.
Article and author information
Author details
Funding
National Eye Institute (DP1EY024503)
- Rafael Yuste
National Institute of Mental Health (R44MH109187)
- Darcy S Peterka
Defense Advanced Research Projects Agency (N66001-15-C-4032)
- Rafael Yuste
National Institute of Mental Health (R01MH100561)
- Rafael Yuste
National Eye Institute (R21EY027592)
- Darcy S Peterka
National Institute of Mental Health (R01MH101218)
- Rafael Yuste
Defense Advanced Research Projects Agency (W91NF-14-1-0269)
- Rafael Yuste
Army Research Laboratory (W911NF-12-1-0594)
- Rafael Yuste
Army Research Office (W911NF-12-1-0594)
- Rafael Yuste
Burroughs Wellcome Fund (1015761)
- Weijian Yang
Uehara Memorial Foundation
- Yuki Bando
National Eye Institute (R01EY011787)
- Rafael Yuste
National Institute of Mental Health (R41MH100895)
- Rafael Yuste
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of Columbia University [protocol ID: AC-AAAM5100, AC-AAAM7951].
Reviewing Editor
- Karel Svoboda, Janelia Research Campus, Howard Hughes Medical Institute, United States
Publication history
- Received: October 10, 2017
- Accepted: February 5, 2018
- Accepted Manuscript published: February 7, 2018 (version 1)
- Version of Record published: March 1, 2018 (version 2)
Copyright
© 2018, Yang 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
-
- 17,762
- Page views
-
- 2,440
- Downloads
-
- 127
- 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
Sensory responses of cortical neurons are more discriminable when evoked on a baseline of desynchronized spontaneous activity, but cortical desynchronization has not generally been associated with more accurate perceptual decisions. Here, we show that mice perform more accurate auditory judgments when activity in the auditory cortex is elevated and desynchronized before stimulus onset, but only if the previous trial was an error, and that this relationship is occluded if previous outcome is ignored. We confirmed that the outcome-dependent effect of brain state on performance is neither due to idiosyncratic associations between the slow components of either signal, nor to the existence of specific cortical states evident only after errors. Instead, errors appear to gate the effect of cortical state fluctuations on discrimination accuracy. Neither facial movements nor pupil size during the baseline were associated with accuracy, but they were predictive of measures of responsivity, such as the probability of not responding to the stimulus or of responding prematurely. These results suggest that the functional role of cortical state on behavior is dynamic and constantly regulated by performance monitoring systems.
-
- Neuroscience
Successive auditory inputs are rarely independent, their relationships ranging from local transitions between elements to hierarchical and nested representations. In many situations, humans retrieve these dependencies even from limited datasets. However, this learning at multiple scale levels is poorly understood. Here, we used the formalism proposed by network science to study the representation of local and higher-order structures and their interaction in auditory sequences. We show that human adults exhibited biases in their perception of local transitions between elements, which made them sensitive to high-order network structures such as communities. This behavior is consistent with the creation of a parsimonious simplified model from the evidence they receive, achieved by pruning and completing relationships between network elements. This observation suggests that the brain does not rely on exact memories but on a parsimonious representation of the world. Moreover, this bias can be analytically modeled by a memory/efficiency trade-off. This model correctly accounts for previous findings, including local transition probabilities as well as high-order network structures, unifying sequence learning across scales. We finally propose putative brain implementations of such bias.