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.
Bibliographical note© 2022 Butcher, Sims, Ngum, Bazzari, Jenkins, King, Hill, Nagel, Fox, Parri and Glazewski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
This study was funded by the BBSRC project grants BB/J018422/1 and BB/J017809/1, the BBSRC travel grant BB/M025675/1, the Physiological Society Travel Grants to SG, and the European Union’s Horizon 2020 Research and Innovation Programme under the grant agreement NEUROPA No: 863214.
Copyright © 2022 Butcher, Sims, Ngum, Bazzari, Jenkins, King, Hill, Nagel, Fox, Parri and Glazewski.
- Cellular Neuroscience
- Hebbian plasticity
- homeostatic plasticity
- synaptic plasticity
- LTD (long term depression)
- LTP (long term potentiation)