Editors' ChoiceNeuroscience

Astrocytes help make memories

Sci. Signal.  31 May 2016:
Vol. 9, Issue 430, pp. ec126
DOI: 10.1126/scisignal.aag2272

The hippocampus is critical to the formation of memories. Memory formation in response to new experiences (as in learning) requires some suppression of retrieval of past memories to avoid interference. Acetylcholine (ACh) is released in the hippocampus when animals have new experiences, and disruption of cholinergic signaling impairs memory formation. Astrocytes perform various functions in the central nervous system, including releasing the neurotransmitter glutamate. Pabst et al. found that astrocytes promote experiential learning by converting cholinergic input into glutamatergic activation of inhibitory interneurons in the hippocampus. Electrophysiological analyses following optogenetic stimulation in either mice or hippocampal slices revealed that ACh release from septal neurons expressing channelrhodopsin-2 induced the activation of inhibitory hilar interneurons and mossy cells and the hyperpolarization (inhibition) of hippocampal dentate granule cells. Pharmacological antagonists confirmed the role of cholinergic and γ-aminobutyric acid (GABA) signaling in these effects between septal projections, interneurons, and dentate granule cells and suggested that a glutamatergic relay mediated this circuit. Optogenetic-induced ACh release in the hippocampus induced nicotinic ACh- and Ca2+-dependent activation of hilar astrocytes, whereas inhibiting astroglial activity through various means suppressed the subsequent activation of hilar interneurons and inhibition of dentate granule cells. The findings reveal astrocytes as intermediaries of a neuronal circuit in vivo that promotes memory formation and learning.

M. Pabst, O. Braganza, H. Dannenberg, W. Hu, L. Pothmann, J. Rosen, I. Mody, K. van Loo, K. Deisseroth, A. J. Becker, S. Schoch, H. Beck, Astrocyte intermediaries of septal cholinergic modulation in the hippocampus. Neuron 90, 853–865 (2016). [PubMed]