Bringing together immediate early genes and sensorimotor response properties in V1
Functional correlates of immediate early gene expression in mouse visual cortex
Recommendation: posted 27 June 2022, validated 26 July 2022
Harris, J. and Keshavarzi, S. (2022) Bringing together immediate early genes and sensorimotor response properties in V1. Peer Community in Neuroscience, 100005. https://doi.org/10.24072/pci.neuro.100005
The primary visual cortex (V1) does not just process vision: it also integrates self-generated motion signals (Niell, Stryker 2010; Keller et al. 2012; Saleem et al. 2013; Vélez-Fort et al. 2018; Meyer et al. 2018), enabling us to match our actions to the world we see. We know that the development of visuomotor representation in V1 depends on experience (Attinger et al. 2017; Widmer et al. 2022), but how exactly does each neuron acquire the right balance of visual and motor input? And how do some neurons become more responsive to visual or motor signals? Mahringer et al. (Mahringer et al. 2022) suspected that the answers may lie in experience-specific plasticity mechanisms.
To investigate this, the authors measured the expression of immediate early genes (IEGs) as indicators of both past neural activity and future plasticity. They examined three IEGs previously implicated in visual cortical plasticity: c-fos, egr1 and Arc (Yamada et al. 1999; Wang et al. 2006; Xie et al. 2014). In three separate transgenic mouse lines, GFP expression was driven by these IEGs, and a red variant of a genetically encoded calcium indicator allowed for simultaneous measurement of neuronal activity. Initial characterisation of IEG expression and calcium fluorescence revealed that IEG levels were only weakly (positively) correlated with visually-evoked neural activity.
But what about the relationship between IEG expression and first visual or visuomotor experience? In dark-reared mice, first visual and visuomotor experiences led to differential IEG expression: Arc expression increased after first visual and visuomotor experiences; EGR1 expression decreased after first visuomotor experience; and c-Fos expression remained largely unchanged. Neural activity levels could not account for these changes, suggesting that different sensory experiences can selectively recruit different IEG expression patterns, perhaps according to input pathway.
Further analysis of those neurons with the highest levels of IEG expression revealed that different IEGs were associated with different functional response properties. High Arc-expressing neurons developed above-average visual and below-average motor responses, while high EGR1-expressing neurons developed above-average motor responses. These results suggest that during experience-dependent wiring, Arc expression drives plasticity favouring bottom-up visual input, while EGR1 expression drives plasticity favouring top-down motor input. Interestingly, while Arc-expressing neurons appear to end up with little-to-no motor input, EGR1-expressing neurons appear to enjoy both visual and motor input, enabling them to display above-average visuomotor mismatch responses.
Overall, this work makes two important advances. First, it suggests that IEG expression may be more closely linked to specific forms of plasticity than general levels of neural activity. Second, it reveals a mechanism by which visual cortical neurons can acquire specific functional properties by selectively upregulating bottom-up or top-down inputs in response to particular sensory experiences.
As an additional note, we would like to highlight a vigorous technical discussion that this manuscript triggered: unconventionally, the authors chose not to apply a neuropil correction procedure to their calcium imaging data. This decision split opinion, amongst both reviewers and recommenders. We have come to the view that the findings are nevertheless of interest for the community and are pleased to point readers towards the publicly available reviews and authors’ responses.
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The recommender in charge of the evaluation of the article and the reviewers declared that they have no conflict of interest (as defined in the code of conduct of PCI) with the authors or with the content of the article. The authors declared that they comply with the PCI rule of having no financial conflicts of interest in relation to the content of the article.
Reviewed by anonymous reviewer 2, 07 Jun 2022
Evaluation round #2
DOI or URL of the preprint: https://doi.org/10.1101/2020.11.12.379909
Version of the preprint: v3
Author's Reply, 20 Apr 2022
Decision by Sepiedeh Keshavarzi and Julia Jade Harris, posted 06 Apr 2022
Thank you for sending your revised manuscript. As you can see from the reviewers’ previous and current comments, the overall assessment has been very positive and reviewer 1 is now happy with your revisions. However, we agree with reviewer's 2 comment regarding neuropil correction as a supplemental figure, even if on a subset of data. Please also address their second concern about correction of baseline responses in the dark. Although we think that implementing their suggestion for presenting data in Figure 4A will improve the paper, this is not a requisite for recommending your manuscript. We look forward to reading your revised paper.
Sepiedeh and Julia
Reviewed by anonymous reviewer 1, 18 Mar 2022
Reviewed by Balázs Hangya, 16 Mar 2022
Evaluation round #1
DOI or URL of the preprint: https://doi.org/10.1101/2020.11.12.379909
Author's Reply, 03 Mar 2022
Decision by Sepiedeh Keshavarzi, posted 01 Feb 2022
Dear Mahringer et al.,
Thank you again for submitting your preprint "Functional correlates of immediate early gene expression in mouse visual cortex" for peer-review at PCI. As you can see from the Reviewers' comments below, your manuscript has been received positively and with enthusiasm. At the same time, the Reviewers have raised a number of concerns and questions that would need to be addressed before the manuscript can be recommended. I hope that you find these comments constructive.