Neuron
Volume 97, Issue 3, 7 February 2018, Pages 670-683.e6
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Article
Anxiety Cells in a Hippocampal-Hypothalamic Circuit

https://doi.org/10.1016/j.neuron.2018.01.016Get rights and content
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Highlights

  • Anxiogenic stimuli are differentially represented along the DV axis of the HPC

  • Inhibition of the vHPC in anxiogenic environments reduces avoidance behavior

  • vCA1 outputs to LHA but not BA control anxiety-related behavior

  • The majority of vCA1-LHA projection neurons represent anxiogenic stimuli

Summary

The hippocampus is traditionally thought to transmit contextual information to limbic structures where it acquires valence. Using freely moving calcium imaging and optogenetics, we show that while the dorsal CA1 subregion of the hippocampus is enriched in place cells, ventral CA1 (vCA1) is enriched in anxiety cells that are activated by anxiogenic environments and required for avoidance behavior. Imaging cells defined by their projection target revealed that anxiety cells were enriched in the vCA1 population projecting to the lateral hypothalamic area (LHA) but not to the basal amygdala (BA). Consistent with this selectivity, optogenetic activation of vCA1 terminals in LHA but not BA increased anxiety and avoidance, while activation of terminals in BA but not LHA impaired contextual fear memory. Thus, the hippocampus encodes not only neutral but also valence-related contextual information, and the vCA1-LHA pathway is a direct route by which the hippocampus can rapidly influence innate anxiety behavior.

Keywords

ventral hippocampus
anxiety
calcium imaging

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13

These authors contributed equally

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