Hippocampal-Prefrontal Theta Transmission Regulates Avoidance Behavior

Nancy Padilla-Coreano; Sarah Canetta; Rachel M Mikofsky; Emily Alway; Johannes Passecker; Maxym V Myroshnychenko; Alvaro L Garcia-Garcia; Richard Warren; Eric Teboul; Dakota R Blackman; Mitchell P Morton; Sofiya Hupalo; Kay M Tye; Christoph Kellendonk; David A Kupferschmidt; Joshua A Gordon

doi:10.1016/j.neuron.2019.08.006

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.

Authors

Nancy Padilla-Coreano¹, Sarah Canetta², Rachel M Mikofsky³, Emily Alway³, Johannes Passecker⁴, Maxym V Myroshnychenko³, Alvaro L Garcia-Garcia⁵, Richard Warren⁵, Eric Teboul⁶, Dakota R Blackman⁵, Mitchell P Morton⁵, Sofiya Hupalo³, Kay M Tye¹, Christoph Kellendonk⁷, David A Kupferschmidt³, Joshua A Gordon⁸

Affiliations

¹ Systems Neuroscience Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
² Department of Psychiatry, Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA.
³ Integrative Neuroscience Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
⁴ Integrative Neuroscience Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA; Zuckerman Mind Brain Behavior Institute, New York, NY 10027, USA.
⁵ Department of Psychiatry, Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA.
⁶ Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA.
⁷ Department of Psychiatry, Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA; Department of Pharmacology, Columbia University Medical Center, 1051 Riverside Drive, New York, NY 10032, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA.
⁸ Integrative Neuroscience Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA; National Institute of Mental Health, NIH, Bethesda, MD 20892, USA. Electronic address: joshua.gordon@nih.gov.

Abstract

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.

Published by Elsevier Inc.

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*

Abstract

Publication types

MeSH terms

Grants and funding