Research Article

Dendritic Inhibition in the Hippocampus Supports Fear Learning

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Science  21 Feb 2014:
Vol. 343, Issue 6173, pp. 857-863
DOI: 10.1126/science.1247485

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Fear, Memory, and Place

Contextual fear conditioning (CFC) is widely used as a hippocampal-dependent classical conditioning task to model human episodic memory. Lovett-Barron et al. (p. 857) combined in vivo imaging with pharmacology, pharmacogenetics, and optogenetics and they found that somatostatin-expressing, dendrite-targeting γ-aminobutyric acid–releasing interneurons in hippocampal area CA1 are required for CFC. During CFC, sensory features of the aversive event reach hippocampal output neurons through excitatory cortical afferents and require active inhibitory filtering to ensure that the hippocampus exclusively encodes the conditioned stimulus.


Fear memories guide adaptive behavior in contexts associated with aversive events. The hippocampus forms a neural representation of the context that predicts aversive events. Representations of context incorporate multisensory features of the environment, but must somehow exclude sensory features of the aversive event itself. We investigated this selectivity using cell type–specific imaging and inactivation in hippocampal area CA1 of behaving mice. Aversive stimuli activated CA1 dendrite-targeting interneurons via cholinergic input, leading to inhibition of pyramidal cell distal dendrites receiving aversive sensory excitation from the entorhinal cortex. Inactivating dendrite-targeting interneurons during aversive stimuli increased CA1 pyramidal cell population responses and prevented fear learning. We propose subcortical activation of dendritic inhibition as a mechanism for exclusion of aversive stimuli from hippocampal contextual representations during fear learning.

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