Lasting Adaptations in Social Behavior Produced by Social Disruption and Inhibition of Adult Neurogenesis

J Neurosci. 2016 Jun 29;36(26):7027-38. doi: 10.1523/JNEUROSCI.4435-15.2016.

Abstract

Research on social instability has focused on its detrimental consequences, but most people are resilient and respond by invoking various coping strategies. To investigate cellular processes underlying such strategies, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Social disruption produced a preference for familiar over novel conspecifics, a change that did not involve global memory impairments or increased anxiety. Using the neuropeptide oxytocin as a tool to increase neurogenesis in the hippocampus of disrupted rats restored preference for novel conspecifics to predisruption levels. Conversely, reducing the number of new neurons by limited inhibition of adult neurogenesis in naive transgenic GFAP-thymidine kinase rats resulted in social behavior similar to disrupted rats. Together, these results provide novel mechanistic evidence that social disruption shapes behavior in a potentially adaptive way, possibly by reducing adult neurogenesis in the hippocampus.

Significance statement: To investigate cellular processes underlying adaptation to social instability, a dominance hierarchy of rats was formed and then destabilized. Regardless of social position, rats from disrupted hierarchies had fewer new neurons in the hippocampus compared with rats from control cages and those from stable hierarchies. Unexpectedly, these changes were accompanied by changes in social strategies without evidence of impairments in cognition or anxiety regulation. Restoring adult neurogenesis in disrupted rats using oxytocin and conditionally suppressing the production of new neurons in socially naive GFAP-thymidine kinase rats showed that loss of 6-week-old neurons may be responsible for adaptive changes in social behavior.

Keywords: GFAP-TK transgenic rats; dominance hierarchy; hippocampus; neurogenesis; oxytocin; social behavior.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adaptation, Psychological / physiology*
  • Animals
  • Anxiety / metabolism
  • Anxiety / pathology
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Hippocampus / cytology*
  • Hydrocortisone / blood
  • Idoxuridine / pharmacology
  • Male
  • Neurogenesis / drug effects
  • Neurogenesis / physiology*
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Oxytocin / pharmacology
  • Phosphopyruvate Hydratase / metabolism
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Rats, Transgenic
  • Social Behavior*
  • Testosterone / blood
  • Vocalization, Animal

Substances

  • Glial Fibrillary Acidic Protein
  • Nucleic Acid Synthesis Inhibitors
  • Testosterone
  • Oxytocin
  • Phosphopyruvate Hydratase
  • Idoxuridine
  • Hydrocortisone