Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks.
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.
Brain Science Institute, RIKEN, Saitama 351-0198, Japan; letellier.mathieu@gmail.com goda@brain.riken.jp.
Mathieu
M
Letellier
Brain Science Institute, RIKEN, Saitama 351-0198, Japan;
Yun Kyung
YK
Park
Brain Science Institute, RIKEN, Saitama 351-0198, Japan;
Thomas E
TE
Chater
Brain Science Institute, RIKEN, Saitama 351-0198, Japan;
Peter H
PH
Chipman
Brain Science Institute, RIKEN, Saitama 351-0198, Japan;
Sunita Ghimire
SG
Gautam
Brain Science Institute, RIKEN, Saitama 351-0198, Japan;
Tomoko
T
Oshima-Takago
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 letellier.mathieu@gmail.com goda@brain.riken.jp.
Yukiko
Y
Goda
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology*
astrocyte; heterosynaptic plasticity; hippocampal neuron; synapse heterogeneity; synaptic strength