Roles of the ventral hippocampus and medial prefrontal cortex in spatial reversal learning and attentional set-shifting

Neurobiol Learn Mem. 2021 Sep;183:107477. doi: 10.1016/j.nlm.2021.107477. Epub 2021 Jun 8.


Neural components enabling flexible cognition and behavior are well-established, and depend mostly on proper intercommunication within the prefrontal cortex (PFC) and striatum. However, dense projections from the ventral hippocampus (vHPC) alter the functioning of the medial PFC (mPFC). Dysfunctional hippocampo-prefrontal connectivity negatively affects the integrity of flexible cognition, especially in patients with schizophrenia. In this study, we aimed to test the role of the vHPC and mPFC in a place avoidance task on a rotating arena using two spatial flexibility task variants - reversal learning and set-shifting. To achieve this, we inactivated each of these structures in adult male Long-Evans rats by performing bilateral local muscimol (a GABAA receptor agonist) injections. A significantly disrupted performance was observed in reversal learning in the vHPC-inactivated, but not in the mPFC-inactivated rats. These results confirm the notion that the vHPC participates in some forms of behavioral flexibility, especially when spatial cues are needed. It seems, rather unexpectedly, that the mPFC is not taxed in these flexibility tasks on a rotating arena.

Keywords: Behavioral flexibility; Carousel; Muscimol; Prefrontal cortex; Rotating arena; Ventral hippocampus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Attention / drug effects
  • Attention / physiology*
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology
  • GABA-A Receptor Agonists / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Male
  • Muscimol / pharmacology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology*
  • Rats
  • Reversal Learning / drug effects
  • Reversal Learning / physiology*
  • Spatial Processing / drug effects
  • Spatial Processing / physiology*


  • GABA-A Receptor Agonists
  • Muscimol