Simultaneous all-optical manipulation and recording of neural circuit activity with cellular resolution in vivo

By Adam Packer, Lloyd E. Russell, H. Dalgleish, Michael Häusser. Nature Methods, 2014

530 citations recorded by the source corpus.

We describe an all-optical strategy for simultaneously manipulating and recording the activity of multiple neurons with cellular resolution in vivo. We performed simultaneous two-photon optogenetic activation and calcium imaging by coexpression of a red-shifted opsin and a genetically encoded calcium indicator. A spatial light modulator allows tens of user-selected neurons to be targeted for spatiotemporally precise concurrent optogenetic activation, while simultaneous fast calcium imaging provides high-resolution network-wide readout of the manipulation with negligible optical cross-talk. Proof-of-principle experiments in mouse barrel cortex demonstrate interrogation of the same neuronal population during different behavioral states and targeting of neuronal ensembles based on their functional signature. This approach extends the optogenetic toolkit beyond the specificity obtained with genetic or viral approaches, enabling high-throughput, flexible and long-term optical interrogation of functionally defined neural circuits with single-cell and single-spike resolution in the mouse brain in vivo.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience

View Paper: https://www.semanticscholar.org/paper/23112f1036e3254ecd9215f5bfd413a39a8366b9

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Citations in the corpus

Challenges and opportunities for large-scale electrophysiology with Neuropixels probes (2018, unknown): “In the future, imaging of membrane-localized voltage sensors [51] or methods to elicit single spikes from individual neurons [52] may provide new ways to collect ground truth with higher throughput.”
Model-based Bayesian inference of neural activity and connectivity from all-optical interrogation of a neural circuit (2017, methodology): “A large subset of the excitatory cells also express channelrhodopsin, which, in combination with two-photon photostimulation, allows cellular resolution activity perturbations [5].”
Predictive Processing: A Canonical Cortical Computation (2018, background): “In this way, one could test the influence of activation of a subset of putative internal representation neurons, either in a given cortical layer or through targeted photostimulation (Packer et al., 2014), on functionally identified prediction error neurons in layer 2/3.”
Sensitive red protein calcium indicators for imaging neural activity (2016, background): “, 2013) is preferable in situations when using a red-shifted light sensitive ion channel and a green GECI produces cross-talk (Rickgauer et al., 2014; Packer et al., 2015).”
From the neuron doctrine to neural networks (2015, background): “…of neural circuits can be carried out while preserving single-cell resolution 172–174 , while simultaneously imaging neuronal activity 172,175 , thus allowing one to ‘play the piano’ with neuronal circuits in order to generate spatiotemporal patterns of activity with the same precision…”
Simultaneous multi-plane imaging of neural circuits (2016, unknown): “The regional targeting is performed remotely, through holography, without any motion of the objective, which makes the technique a strong complement to 3D two-photon activation (Packer et al., 2012; Rickgauer et al., 2014; Packer et al., 2015).”
NoRMCorre: An online algorithm for piecewise rigid motion correction of calcium imaging data (2017, background): “Consequently it is suitable for online regis35 tration of high volume streaming data, a useful feature that can facilitate 36 fully closed loop optical interrogation experiments [12] or compensate for 37 limited amounts of available memory.”
Closed-loop and activity-guided optogenetic control. (2015, unknown): “Used in combination (Rickgauer et al., 2014; Packer et al., 2015), it is possible to all-optically stimulate and record at least ten neurons simultaneously every 10–20 ms (Packer et al., 2015) using the scanning, multifocus-phase SLM approach described above.”