Morphological, structural, and functional alterations of the prefrontal cortex and the basolateral amygdala after early lesion of the rat mediodorsal thalamus

Brain Struct Funct. 2017 Aug;222(6):2527-2545. doi: 10.1007/s00429-016-1354-2. Epub 2017 Feb 1.


Early postnatal damage to the mediodorsal thalamus (MD) produces deficits in cognition and behavior believed to be associated with early prefrontal cortical maldevelopment. We assessed the role of MD afferents during development on the morphological and functional maturation of the prefrontal cortex (PFC) and the basolateral amygdala (BLA). Sprague-Dawley rat pups (n = 56) received a bilateral electrolytic lesion of the MD or a MD Sham lesion on postnatal day 4. 7 weeks later, all rats were tested in anxiety-related and cognitive paradigms using the elevated plus maze and novel object recognition tests. Following behavioral testing (P70), rats were killed and the baseline expression of C-Fos protein and the number of GABAergic neurons were evaluated in the PFC and the BLA. The dendritic morphology and spine density in the PFC using Golgi-Cox staining was also evaluated. Adult rats with early postnatal bilateral MD damage exhibited disrupted recognition memory and increased anxiety-like behaviors. The lesion also caused a significant diminution of C-Fos immunolabeling and an increase of the number of GABAergic neurons in the PFC. In the BLA, the number of GABAergic neurons was significantly reduced, associated with an increase in C-Fos immunolabeling. Furthermore, in the PFC the lesion induced a significant reduction in dendritic branching and spine density. Our data are consistent with the hypothesis that the MD plays a role in the development of the PFC and, therefore, may be a good animal model to investigate cognitive symptoms associated with schizophrenia.

Keywords: Basolateral amygdala; Golgi-Cox; Lesion; Mediodorsal thalamus; Prefrontal cortex; Schizophrenia.

MeSH terms

  • Animals
  • Animals, Newborn
  • Anxiety / pathology
  • Anxiety / physiopathology
  • Anxiety / psychology
  • Basolateral Nuclear Complex / metabolism
  • Basolateral Nuclear Complex / pathology
  • Basolateral Nuclear Complex / physiopathology*
  • Behavior, Animal*
  • Cognition
  • Dendritic Spines / metabolism
  • Dendritic Spines / pathology
  • Disease Models, Animal
  • Electric Stimulation
  • GABAergic Neurons / metabolism
  • GABAergic Neurons / pathology
  • Maze Learning
  • Mediodorsal Thalamic Nucleus / metabolism
  • Mediodorsal Thalamic Nucleus / pathology
  • Mediodorsal Thalamic Nucleus / physiopathology*
  • Neural Pathways / metabolism
  • Neural Pathways / pathology
  • Neural Pathways / physiopathology
  • Neurons, Afferent / metabolism
  • Neurons, Afferent / pathology
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / pathology
  • Prefrontal Cortex / physiopathology*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats, Sprague-Dawley
  • Recognition, Psychology
  • Schizophrenia / metabolism
  • Schizophrenia / pathology
  • Schizophrenia / physiopathology*
  • Schizophrenic Psychology
  • gamma-Aminobutyric Acid / metabolism


  • Proto-Oncogene Proteins c-fos
  • gamma-Aminobutyric Acid