Abstract
Multiple cortical areas contribute to visual processing in mice. However, the functional organization and development of higher visual areas are unclear. Here we used intrinsic signal optical imaging and two-photon calcium imaging to map visual responses in adult and developing mice. We found that visually driven activity was well correlated among higher visual areas within two distinct subnetworks resembling the dorsal and ventral visual streams. Visual response magnitude in dorsal stream areas slowly increased over the first 2 weeks of visual experience. By contrast, ventral stream areas exhibited strong responses shortly after eye opening. Neurons in a dorsal stream area showed little change in their tuning sharpness to oriented gratings while those in a ventral stream area increased stimulus selectivity and expanded their receptive fields significantly. Together, these findings provide a functional basis for grouping subnetworks of mouse visual areas and revealed stream differences in the development of receptive field properties.
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Acknowledgements
We are grateful to D. Ferster for generously providing software for intrinsic signal optical imaging and to J. Stirman for customizing the software for these experiments. We thank B. Philpot, P. Manis and J. Stirman for discussion and comments on the manuscript and C. Mazzone for early contributions to the project. I.T.S. was supported by a Helen Lyng White Fellowship. L.B.S. was supported by a fellowship from the Howard Hughes Medical Institute/UNC-Chapel Hill Med into Grad program and by the NIH (T32NS007431). Work by R.H. and H.Z. was partially supported by the NIH (MH086633) and the NSF (SES-1357666 and DMS-1407655). This work was supported by a Career Development Award from the Human Frontier Science Program to S.L.S. (CDA 00063/2012) and by grants from the Whitehall Foundation and the NIH (R01EY024294, R01NS091335) (S.L.S.).
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I.T.S. and S.L.S. conceived and designed the experiments. I.T.S. and L.B.T. performed the intrinsic signal optical imaging experiments and analyzed data. I.T.S. and S.L.S. performed the calcium imaging experiments and analyzed data. R.H. and H.Z. performed some of the statistical analysis. I.T.S. and S.L.S. interpreted the data and wrote the paper.
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Integrated supplementary information
Supplementary Figure 1 Quantifications of responses are reproducible between experts
Two experts (I.T.S. and L.B.T.), blind to the age and conditions, independently quantified the same data set. They drew the boundaries of V1 and HVAs according to the retinotopic maps, and quantified responses to gratings and kinematograms. Their quantifications were highly correlated, demonstrating the robustness of this approach.
Supplementary Figure 2 Activity in HVAs correlates with activity in V1
Visual response magnitudes in HVAs in response to drifting gratings (a) and moving dot kinematograms (b) were well correlated (Pearson’s R) with response magnitudes in V1 within the same maps. All data are from adult mice.
Supplementary Figure 3 Intrinsic signal magnitude as affected by increasing isoflurane concentration
Response magnitude in (a) dorsal stream HVAs and (b) ventral stream HVAs declined with increasing concentrations of isoflurane anesthetic. Normalization of response magnitudes in (c) dorsal stream HVAs and (d) ventral stream HVAs to those in V1 for each map, resulted in measurements that varied less with isoflurane concentration. Shaded region indicates SEM.
Supplementary Figure 4 Skull thickness by age
In mice, the occipital skull rapidly thickens around age P20, which precludes high fidelity transcranial imaging. Thus, for ages beyond P20, chronic or acute craniotomy preparations were made prior to imaging. Shaded region indicates SEM.
Supplementary Figure 5 Developmental time course of individual HVAs
The developmental time course of individual (a) dorsal and (b) ventral stream HVAs shows that the overall trends of dorsal stream HVA development lagging that of ventral stream HVAs are apparent at the single cortical area level. Shaded region indicates SEM.
Supplementary Figure 6 Direction selectivity index changes in areas V1, LM and PM from P20 to P36
(a) Population data for direction selectivity in areas V1, LM, and PM at P20 and P36 for 0.04 cycles/degree and (b) 0.32 cycles/degree gratings are shown. Both cumulative histograms (top rows) and bar graphs (bottom rows; mean ± SEM) are shown for each data set.
Supplementary Figure 7 Additional quantification of RF subregion metrics in areas V1, LM and PM at P20 and P36
(a) Average radius, (b) half long axis, and (c) half short axis measurements for RF subregions in areas V1, LM, and PM at ages P20 and P36. Each box plot indicates the median (thick line), the range of the middle two quartiles (shaded boxes), and the full data range (whiskers).
Supplementary Figure 8 Delay-to-peak responses of receptive field subregions are comparable in areas V1, LM and PM from P20 to P36
In the reverse correlation analysis to recover RF subregions, the time delay between visual stimulus and activity that yielded the strongest RF subregions (measured by Z-score) was similar across areas (V1, LM, and PM), ages (P20 and P36), and subregion signs (ON and OFF). Each box plot indicates the median (thick line), the range of the middle two quartiles (shaded boxes), and the full data range (whiskers).
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Smith, I., Townsend, L., Huh, R. et al. Stream-dependent development of higher visual cortical areas. Nat Neurosci 20, 200–208 (2017). https://doi.org/10.1038/nn.4469
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DOI: https://doi.org/10.1038/nn.4469
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