Astrocyte GluN2C NMDA receptors control basal synaptic strengths of hippocampal CA1 pyramidal neurons in the stratum radiatum

eLife

Kenji Sakimura¹  Manabu Abe¹  Chi Chung Alan Fung²  Tomoki Fukai²  Sunita Ghimire Gautam³  Yukiko Goda³  Angelo Tedoldi³  Peter H Chipman³  Abhilash Sawant³  Alejandra Pazo Fernandez³  Mizuki Kurosawa³  Atsushi Kawai³ 

[1] Department of Animal Model Development, Brain Research Institute, Niigata University, Niigata, Japan;Neural Coding and Brain Computing Unit, Okinawa Institute of Science and Technology Graduate University, Onna-son, Japan;RIKEN Center for Brain Science, Wako-shi, Saitama, Japan;

关键词: basal synaptic strength;    hippocampus;    astrocytes;    NMDA receptors;    GluN2C;    stratum radiatum;    Mouse;   

DOI  :  10.7554/eLife.70818

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Experience-dependent plasticity is a key feature of brain synapses for which neuronal N-Methyl-D-Aspartate receptors (NMDARs) play a major role, from developmental circuit refinement to learning and memory. Astrocytes also express NMDARs, although their exact function has remained controversial. Here, we identify in mouse hippocampus, a circuit function for GluN2C NMDAR, a subtype highly expressed in astrocytes, in layer-specific tuning of synaptic strengths in CA1 pyramidal neurons. Interfering with astrocyte NMDAR or GluN2C NMDAR activity reduces the range of presynaptic strength distribution specifically in the stratum radiatum inputs without an appreciable change in the mean presynaptic strength. Mathematical modeling shows that narrowing of the width of presynaptic release probability distribution compromises the expression of long-term synaptic plasticity. Our findings suggest a novel feedback signaling system that uses astrocyte GluN2C NMDARs to adjust basal synaptic weight distribution of Schaffer collateral inputs, which in turn impacts computations performed by the CA1 pyramidal neuron.

【 授权许可】

CC BY