Dysregulation of hippocampal adult-born immature neurons disrupts a brain-wide network for spatial memory

Bao, H.; Hu, Z.; Lee, S.-h.; Kolagani, R.; Chao, T.-H. H.; Luo, Y.-J.; Ban, W.; Sullivan, H. A.; Gamero-Alameda, S.; Lybrand, Z. R.; Yu, Y.; Hsieh, J.; Wickersham, I. R.; Brenner, S. E.; Shih, Y.-Y. I.; Song, J.

doi:10.1101/2020.09.02.273649

bioRxiv · 10.1101/2020.09.02.273649

Dysregulation of hippocampal adult-born immature neurons disrupts a brain-wide network for spatial memory

Bao, H.·Hu, Z.·Lee, S.-h.·Kolagani, R.·Chao, T.-H. H.·Luo, Y.-J.·Ban, W.·Sullivan, H. A.·Gamero-Alameda, S.·Lybrand, Z. R.·Yu, Y.·Hsieh, J.·Wickersham, I. R.·Brenner, S. E.·Shih, Y.-Y. I.·Song, J.

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Abstract

Mounting evidence suggests that cognitive deficits associated with various neurological disorders may arise in part from a small population of dysregulated adult-born neurons in the dentate gyrus (DG). How these dysregulated adult-born neurons contribute to brain-wide network maladaptation and subsequent cognitive deficits remains unknown. Using an established mouse model with a small number of time-stamped dysregulated adult-born immature neurons and spatial memory deficits, we performed resting state functional magnetic resonance imaging and found that approximately 500 deficient immature neurons (<0.1% of total DG granule neurons) are sufficient to induce a significant decrease in the functional connectivity between DG and insular cortex (IC), two brain regions without direct anatomical connections. Furthermore, using a combination of rabies-based retrograde tracing and in vivo fiber photometry recording, we demonstrated that dysregulated adult-born neurons induce aberrant activity and synchrony in local hippocampal CA3 and CA1 regions, as well as distal medial-dorsal thalamus and IC regions during a spatial memory process. These results suggest that a few hundred dysregulated adult-born immature neurons can impact brain-wide network dynamics across several anatomically discrete regions and collectively contribute to impaired cognitive functions.

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Bao, H., Hu, Z., Lee, S.-h., Kolagani, R., Chao, T.-H. H., Luo, Y.-J., Ban, W., Sullivan, H. A., Gamero-Alameda, S., Lybrand, Z. R., Yu, Y., Hsieh, J., Wickersham, I. R., Brenner, S. E., Shih, Y.-Y. I., Song, J.. 2020-09-03. Dysregulation of hippocampal adult-born immature neurons disrupts a brain-wide network for spatial memory. https://doi.org/10.1101/2020.09.02.273649

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