Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks
Proc Natl Acad Sci USA. 2016-04-26; 113(19): E2685-E2694
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Letellier M(1), Park YK(2), Chater TE(2), Chipman PH(2), Gautam SG(2), Oshima-Takago T(2), Goda Y(3).
(1)Brain Science Institute, RIKEN, Saitama 351-0198, Japan; .
(2)Brain Science Institute, RIKEN, Saitama 351-0198, Japan;
(3)Brain Science Institute, RIKEN, Saitama 351-0198, Japan; Saitama University Brain Science Institute, Saitama University, Saitama 338-8570, Japan; Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Tokyo 153-8902, Japan .
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 Ca(2+)
signaling involving NMDAR activation, astrocyte membrane depolarization, and
L-type Ca(2+) channels. Intracellular infusion of NMDARs or Ca(2+)-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.