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. 2018 Jul 31;115(31):8015-8018.
doi: 10.1073/pnas.1803224115. Epub 2018 Jul 16.

Hippocampus-dependent Emergence of Spatial Sequence Coding in Retrosplenial Cortex

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Free PMC article

Hippocampus-dependent Emergence of Spatial Sequence Coding in Retrosplenial Cortex

Dun Mao et al. Proc Natl Acad Sci U S A. .
Free PMC article

Abstract

Retrosplenial cortex (RSC) is involved in visuospatial integration and spatial learning, and RSC neurons exhibit discrete, place cell-like sequential activity that resembles the population code of space in hippocampus. To investigate the origins and population dynamics of this activity, we combined longitudinal cellular calcium imaging of dysgranular RSC neurons in mice with excitotoxic hippocampal lesions. We tracked the emergence and stability of RSC spatial activity over consecutive imaging sessions. Overall, spatial activity in RSC was experience-dependent, emerging gradually over time, but, as seen in the hippocampus, the spatial code changed dynamically across days. Bilateral but not unilateral hippocampal lesions impeded the development of spatial activity in RSC. Thus, the emergence of spatial activity in RSC, a major recipient of hippocampal information, depends critically on an intact hippocampus; the indirect connections between the dysgranular RSC and the hippocampus further indicate that hippocampus may exert such influences polysynaptically within neocortex.

Keywords: hippocampal indexing theory; hippocampus; retrosplenial cortex; spatial learning; spatial sequence coding.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Experimental design and retrosplenial place cell activity. (A) Treadmill locomotion assay. Two-photon calcium imaging was performed in head-fixed mice running on a treadmill belt endowed with tactile cues. (B) Cellular imaging of neuronal activity through a glass window in RSC in both hemispheres in mice with intact hippocampus (control), unilateral hippocampal lesion (unilesion), and bilateral hippocampal lesions (bilesion). (C) Scatter plot of the remaining volume (normalized) of the hippocampus in the left and right hemispheres. Colors correspond to animal groups shown in B. (D) Mean movement speed profiles as a function of position for the three experimental groups. Error bars are SEM over animals. (E) Calcium time courses (raw and deconvolved) of an example RSC place cell. Position and speed traces are shown below. deconv, deconvolved; norm, normalized.
Fig. 2.
Fig. 2.
Unilateral hippocampal lesion does not impair ipsilateral RSC place cell activity. (A) (Top) Raw calcium time courses of 229 simultaneously imaged RSC neurons in the intact hemisphere of an example unilesion mouse. Neurons were sorted by the positions that elicited their maximum responses. (Bottom) Real (blue) and Bayesian decoded (red) position traces. (B) The same as A but for the lesioned hemisphere RSC of the same mouse. (C) Mean place cell fractions and position decoding errors in unilesion mice. Note that two mouse lines were used here (Thy1 and Ai93). Error bars are SEM over sessions. For unknown reasons, there were intrinsic differences between these lines in the observed place cell fractions.
Fig. 3.
Fig. 3.
Bilateral hippocampal lesions severely impair place cell activity in RSC. (A) (Top) Raw calcium time courses of 255 simultaneously imaged RSC neurons from an example control mouse. Neurons were sorted by the positions that elicited their maximum responses. (Bottom) Real (blue) and Bayesian decoded (red) position traces. (B) The same as A but from an example bilateral lesion mouse. (C) (Left) Mean place cell fractions of individual mice in the control and bilesion groups (all Thy1 mice). Error bars are SEM over sessions. (Right) Bar plots of the average place cell fractions for the two groups. Error bars are SEM over animals. (D) The same as C but for decoding errors. (E) Bar plot of the mean place field width. Colored dots correspond to the mean place field width of individual mice in the control and bilesion groups. (F) The same as E but for the mean spatial information of identified place cells in each animal.
Fig. 4.
Fig. 4.
Hippocampal destruction disrupts experience-dependent emergence of spatial coding in RSC. (A) Average fluorescence images (centered on the target neuron) and position activity maps of the target neuron imaged on days 1, 3, 5, and 7. Position tuning curves (white traces) are overlaid on the position activity maps. (B) Sorted, trial-averaged position activity maps for all RSC place cells from an example control mouse on days 1, 3, 5, and 7. Same neuronal population was imaged across days. Neurons were selected and sorted by corresponding days. (C) Population vector correlation matrices between days for data shown in B. (D) Mean place cell fractions and decoding errors as a function of imaging session for the control and bilateral lesion animals. Error bars are SEM over animals. (E) Mean population vector correlations of the same position (distance < 15 cm, dashed area in SI Appendix, Fig. S5C) and mean position tuning (white traces in A) correlations for all place cells as a function of different imaging intervals. Error bars are SEM over animals. norm, normalized; Pop Vec Corr, population vector correlation.

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