Conditions and constraints for astrocyte calcium signaling in the hippocampal mossy fiber pathway

Neuron. 2014 Apr 16;82(2):413-29. doi: 10.1016/j.neuron.2014.02.041.


The spatiotemporal activities of astrocyte Ca²⁺ signaling in mature neuronal circuits remain unclear. We used genetically encoded Ca²⁺ and glutamate indicators as well as pharmacogenetic and electrical control of neurotransmitter release to explore astrocyte activity in the hippocampal mossy fiber pathway. Our data revealed numerous localized, spontaneous Ca²⁺ signals in astrocyte branches and territories, but these were not driven by neuronal activity or glutamate. Moreover, evoked astrocyte Ca²⁺ signaling changed linearly with the number of mossy fiber action potentials. Under these settings, astrocyte responses were global, suppressed by neurotransmitter clearance, and mediated by glutamate and GABA. Thus, astrocyte engagement in the fully developed mossy fiber pathway was slow and territorial, contrary to that frequently proposed for astrocytes within microcircuits. We show that astrocyte Ca²⁺ signaling functionally segregates large volumes of neuropil and that these transients are not suited for responding to, or regulating, single synapses in the mossy fiber pathway.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Astrocytes / ultrastructure
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Excitatory Amino Acid Agents / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Female
  • GABA Agents / pharmacology
  • Glutamic Acid / metabolism
  • Glutamic Acid / pharmacology
  • Hippocampus / cytology*
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mossy Fibers, Hippocampal / drug effects
  • Mossy Fibers, Hippocampal / physiology*
  • Receptors, GABA-B / genetics
  • Receptors, Metabotropic Glutamate / genetics
  • Sodium Channel Blockers / pharmacology
  • gamma-Aminobutyric Acid / metabolism
  • gamma-Aminobutyric Acid / pharmacology


  • Excitatory Amino Acid Agents
  • GABA Agents
  • Receptors, GABA-B
  • Receptors, Metabotropic Glutamate
  • Sodium Channel Blockers
  • metabotropic glutamate receptor 2
  • metabotropic glutamate receptor 3
  • Glutamic Acid
  • gamma-Aminobutyric Acid