Goal-oriented searching mediated by ventral hippocampus early in trial-and-error learning

Nat Neurosci. 2012 Nov;15(11):1563-71. doi: 10.1038/nn.3224. Epub 2012 Sep 23.


Most behavioral learning in biology is trial and error, but how these learning processes are influenced by individual brain systems is poorly understood. Here we show that ventral-to-dorsal hippocampal subdivisions have specific and sequential functions in trial-and-error maze navigation, with ventral hippocampus (vH) mediating early task-specific goal-oriented searching. Although performance and strategy deployment progressed continuously at the population level, individual mice showed discrete learning phases, each characterized by particular search habits. Transitions in learning phases reflected feedforward inhibitory connectivity (FFI) growth occurring sequentially in ventral, then intermediate, then dorsal hippocampal subdivisions. FFI growth at vH occurred abruptly upon behavioral learning of goal-task relationships. vH lesions or the absence of vH FFI growth delayed early learning and disrupted performance consistency. Intermediate hippocampus lesions impaired intermediate place learning, whereas dorsal hippocampus lesions specifically disrupted late spatial learning. Trial-and-error navigational learning processes in naive mice thus involve a stereotype sequence of increasingly precise subtasks learned through distinct hippocampal subdivisions. Because of its unique connectivity, vH may relate specific goals to internal states in learning under healthy and pathological conditions.

MeSH terms

  • Animals
  • Benzazepines / pharmacology
  • Brain Mapping
  • Conditioning, Psychological / physiology
  • Cytoskeletal Proteins
  • Dopamine Antagonists / pharmacology
  • Exploratory Behavior / physiology*
  • Fear
  • Goals*
  • Green Fluorescent Proteins / genetics
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Learning / physiology*
  • Male
  • Maze Learning / physiology
  • Mice
  • Mice, Transgenic
  • Microfilament Proteins / deficiency
  • Neural Inhibition / genetics
  • Neural Inhibition / physiology
  • Neurons / physiology
  • Phosphopyruvate Hydratase / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism
  • Time Factors


  • Add2 protein, mouse
  • Benzazepines
  • Cytoskeletal Proteins
  • Dopamine Antagonists
  • Microfilament Proteins
  • Proto-Oncogene Proteins c-fos
  • SCH 23390
  • Green Fluorescent Proteins
  • Phosphopyruvate Hydratase