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A requirement for astrocyte IP3R2 signaling for whisker experience-dependent depression and homeostatic upregulation in the mouse barrel cortex.

Butcher, John; Sims, Robert; Ngum, Neville; Bazzari, Amjad H.; Jenkins, Stuart I.; King, Marianne; Hill, Eric J.; Nagel, David A.; Fox, Kevin; Rheinallt Parri, H.; Glazewski

A requirement for astrocyte IP3R2 signaling for whisker experience-dependent depression and homeostatic upregulation in the mouse barrel cortex. Thumbnail


Authors

John Butcher

Robert Sims

Neville Ngum

Amjad H. Bazzari

Marianne King

Eric J. Hill

David A. Nagel

Kevin Fox

H. Rheinallt Parri

Glazewski



Abstract

Changes to sensory experience result in plasticity of synapses in the cortex. This experience-dependent plasticity (EDP) is a fundamental property of the brain. Yet, while much is known about neuronal roles in EDP, very little is known about the role of astrocytes. To address this issue, we used the well-described mouse whiskers-to-barrel cortex system, which expresses a number of forms of EDP. We found that all-whisker deprivation induced characteristic experience-dependent Hebbian depression (EDHD) followed by homeostatic upregulation in L2/3 barrel cortex of wild type mice. However, these changes were not seen in mutant animals (IP3R2-/-) that lack the astrocyte-expressed IP3 receptor subtype. A separate paradigm, the single-whisker experience, induced potentiation of whisker-induced response in both wild-type (WT) mice and IP3R2-/- mice. Recordings in ex vivo barrel cortex slices reflected the in vivo results so that long-term depression (LTD) could not be elicited in slices from IP3R2-/- mice, but long-term potentiation (LTP) could. Interestingly, 1 Hz stimulation inducing LTD in WT paradoxically resulted in NMDAR-dependent LTP in slices from IP3R2-/- animals. The LTD to LTP switch was mimicked by acute buffering astrocytic [Ca2+] i in WT slices. Both WT LTD and IP3R2-/- 1 Hz LTP were mediated by non-ionotropic NMDAR signaling, but only WT LTD was P38 MAPK dependent, indicating an underlying mechanistic switch. These results demonstrate a critical role for astrocytic [Ca2+] i in several EDP mechanisms in neocortex.

Citation

Butcher, J., Sims, R., Ngum, N., Bazzari, A. H., Jenkins, S. I., King, M., …Glazewski. (2022). A requirement for astrocyte IP3R2 signaling for whisker experience-dependent depression and homeostatic upregulation in the mouse barrel cortex. Frontiers in Cellular Neuroscience, 16, Article 905285. https://doi.org/10.3389/fncel.2022.905285

Journal Article Type Article
Acceptance Date Jul 6, 2022
Publication Date Aug 25, 2022
Journal Frontiers in Cellular Neuroscience
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 16
Article Number 905285
DOI https://doi.org/10.3389/fncel.2022.905285
Keywords Hebbian plasticity; homeostatic plasticity; synaptic plasticity; LTD (long term depression); LTP (long term potentiation); BCM; somatosensory
Publisher URL https://www.frontiersin.org/articles/10.3389/fncel.2022.905285/full

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