Direct Ventral Hippocampal-Prefrontal Input Is Required for Anxiety-Related Neural Activity and Behavior

Neuron. 2016 Feb 17;89(4):857-66. doi: 10.1016/j.neuron.2016.01.011. Epub 2016 Feb 4.


The ventral hippocampus (vHPC), medial prefrontal cortex (mPFC), and basolateral amygdala (BLA) are each required for the expression of anxiety-like behavior. Yet the role of each individual element of the circuit is unclear. The projection from the vHPC to the mPFC has been implicated in anxiety-related neural synchrony and spatial representations of aversion. The role of this projection was examined using multi-site neural recordings combined with optogenetic terminal inhibition. Inhibition of vHPC input to the mPFC disrupted anxiety and mPFC representations of aversion, and reduced theta synchrony in a pathway-, frequency- and task-specific manner. Moreover, bilateral, but not unilateral, inhibition altered physiological correlates of anxiety in the BLA, mimicking a safety-like state. These results reveal a specific role for the vHPC-mPFC projection in anxiety-related behavior and the spatial representation of aversive information within the mPFC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Anxiety / pathology*
  • Anxiety / physiopathology*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Disease Models, Animal
  • Evoked Potentials / physiology
  • Food Deprivation
  • Functional Laterality
  • Hippocampus / pathology*
  • Male
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred C57BL
  • Neural Inhibition / physiology
  • Neural Pathways / physiology*
  • Neurons / physiology*
  • Prefrontal Cortex / pathology*
  • Reaction Time / physiology
  • Statistics, Nonparametric
  • Theta Rhythm / physiology


  • Calcium-Calmodulin-Dependent Protein Kinase Type 2