Distinct and Dynamic ON and OFF Neural Ensembles in the Prefrontal Cortex Code Social Exploration

Neuron. 2018 Nov 7;100(3):700-714.e9. doi: 10.1016/j.neuron.2018.08.043. Epub 2018 Sep 27.


The medial prefrontal cortex (mPFC) is important for social behavior, but the mechanisms by which mPFC neurons code real-time social exploration remain largely unknown. Here we utilized miniScopes to record calcium activities from hundreds of excitatory neurons in the mPFC while mice freely explored restrained social targets in the absence or presence of the psychedelic drug phencyclidine (PCP). We identified distinct and dynamic ON and OFF neural ensembles that displayed opposing activities to code real-time behavioral information. We further illustrated that ON and OFF ensembles tuned to social exploration carried information of salience and novelty for social targets. Finally, we showed that dysfunctions in these ensembles were associated with abnormal social exploration elicited by PCP. Our findings underscore the importance of mPFC ON and OFF neural ensembles for proper exploratory behavior, including social exploration, and pave the way for future studies elucidating neural circuit dysfunctions in psychiatric disorders.

Keywords: decoding; freely behaving; in vivo calcium imaging; miniature fluorescence microscope; mouse model; preference for social novelty; schizophrenia; sociability.

Publication types

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

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Animals
  • Excitatory Amino Acid Antagonists / pharmacology
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Nerve Net / chemistry
  • Nerve Net / drug effects
  • Nerve Net / physiology*
  • Optogenetics / methods
  • Phencyclidine / pharmacology
  • Prefrontal Cortex / chemistry
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology*
  • Social Behavior*


  • Excitatory Amino Acid Antagonists
  • Phencyclidine