期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 19, 页码 E2685-E2694出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1523717113
关键词
synapse heterogeneity; synaptic strength; astrocyte; hippocampal neuron; heterosynaptic plasticity
资金
- Medical Research Council UK
- European Union [HEALTHF-2-2009-241498]
- RIKEN Brain Science Institute
- JSPS
- MEXT [15H04280]
- Brain/MINDS from the Japan AMED
- Grants-in-Aid for Scientific Research [15H04280, 14F04760] Funding Source: KAKEN
- Medical Research Council [MC_CF12266] Funding Source: researchfish
Dendrites are neuronal structures specialized for receiving and processing information through their many synaptic inputs. How input strengths are modified across dendrites in ways that are crucial for synaptic integration and plasticity remains unclear. We examined in single hippocampal neurons the mechanism of heterosynaptic interactions and the heterogeneity of synaptic strengths of pyramidal cell inputs. Heterosynaptic presynaptic plasticity that counterbalances input strengths requires N-methyl-D-aspartate receptors (NMDARs) and astrocytes. Importantly, this mechanism is shared with the mechanism for maintaining highly heterogeneous basal presynaptic strengths, which requires astrocyte Ca2+ signaling involving NMDAR activation, astrocyte membrane depolarization, and L-type Ca2+ channels. Intracellular infusion of NMDARs or Ca2+-channel blockers into astrocytes, conditionally ablating the GluN1 NMDAR subunit, or optogenetically hyperpolarizing astrocytes with archaerhodopsin promotes homogenization of convergent presynaptic inputs. Our findings support the presence of an astrocyte-dependent cellular mechanism that enhances the heterogeneity of presynaptic strengths of convergent connections, which may help boost the computational power of dendrites.
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