The hippocampal-prefrontal pathway: the weak link in psychiatric disorders?

Eur Neuropsychopharmacol. 2013 Oct;23(10):1165-81. doi: 10.1016/j.euroneuro.2012.10.018. Epub 2013 Jan 15.


While the hippocampal formation and the prefrontal cortex each have a well-established role in cognitive and mnemonic processes, the extent and manner in which these structures interact to achieve these functions has not been fully delineated. Recent research in rodents compellingly supports the idea that the projection of neurons extending from the CA1 region of the hippocampus and from the subiculum to the prefrontal cortex, referred to here as the H-PFC pathway, is critically involved in aspects of cognition related to executive function and to emotional regulation. Concurrently, it is becoming evident that persons suffering from schizophrenia, depression, and post-traumatic stress disorder display structural anomalies and aberrant functional coupling within the hippocampal-prefrontal circuit. Considering that these disorders involve varying degrees of cognitive impairment and emotional dysregulation, dysfunction in the H-PFC pathway might therefore be the common element of their pathophysiology. This overlap might also be intertwined with the pathway's evident susceptibility to stress and with its relationship to the amygdala. In consequence, the H-PFC pathway is a potentially crucial element of the pathophysiology of several psychiatric diseases, and it offers a specific target for therapeutic intervention, which is consistent with the recent emphasis on reframing psychiatric diseases in terms of brain circuits.

Keywords: Depression; Hippocampus; Pathophysiology; Post-traumatic stress disorder; Prefrontal cortex; Schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Depressive Disorder, Major / metabolism
  • Depressive Disorder, Major / physiopathology
  • Evidence-Based Medicine*
  • Fear
  • Hippocampus / metabolism*
  • Hippocampus / physiopathology
  • Humans
  • Learning
  • Limbic System / metabolism
  • Limbic System / physiopathology
  • Memory, Short-Term
  • Mental Disorders / metabolism*
  • Mental Disorders / physiopathology
  • Models, Neurological*
  • Neuronal Plasticity
  • Neurons / metabolism*
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / physiopathology
  • Reward
  • Schizophrenia / metabolism
  • Schizophrenia / physiopathology
  • Stress Disorders, Post-Traumatic / metabolism
  • Stress Disorders, Post-Traumatic / physiopathology
  • Synaptic Transmission*