Hippocampal-Prefrontal Theta Transmission Regulates Avoidance Behavior

Neuron. 2019 Nov 6;104(3):601-610.e4. doi: 10.1016/j.neuron.2019.08.006. Epub 2019 Sep 11.


Long-range synchronization of neural oscillations correlates with distinct behaviors, yet its causal role remains unproven. In mice, tests of avoidance behavior evoke increases in theta-frequency (∼8 Hz) oscillatory synchrony between the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC). To test the causal role of this synchrony, we dynamically modulated vHPC-mPFC terminal activity using optogenetic stimulation. Oscillatory stimulation at 8 Hz maximally increased avoidance behavior compared to 2, 4, and 20 Hz. Moreover, avoidance behavior was selectively increased when 8-Hz stimulation was delivered in an oscillatory, but not pulsatile, manner. Furthermore, 8-Hz oscillatory stimulation enhanced vHPC-mPFC neurotransmission and entrained neural activity in the vHPC-mPFC network, resulting in increased synchrony between vHPC theta activity and mPFC spiking. These data suggest a privileged role for vHPC-mPFC theta-frequency communication in generating avoidance behavior and provide direct evidence that synchronized oscillations play a role in facilitating neural transmission and behavior.

Keywords: anxiety; avoidance; hippocampus; medial prefrontal cortex; optogenetics; oscillations; synchrony; theta.

Publication types

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

MeSH terms

  • Animals
  • Avoidance Learning / physiology*
  • Electrophysiological Phenomena / physiology*
  • Hippocampus / physiology*
  • Maze Learning
  • Mice
  • Optogenetics
  • Prefrontal Cortex / physiology*
  • Synaptic Transmission
  • Theta Rhythm / physiology*