Early Lesion of the Reticular Thalamic Nucleus Disrupts the Structure and Function of the Mediodorsal Thalamus and Prefrontal Cortex

Dev Neurobiol. 2019 Nov;79(11-12):913-933. doi: 10.1002/dneu.22733. Epub 2020 Feb 3.

Abstract

The thalamic reticular nucleus (TRN), part of the thalamus, is a thin GABAergic cell layer adjacent to the relay nuclei of the dorsal thalamus. It receives input from the cortex and other thalamic nuclei and provides major inhibitory input to each thalamic nucleus, particularly the mediodorsal nucleus (MD). As the MD is important for supporting optimal cortico-thalamo-cortical interactions during brain maturation, we hypothesized that that early damage to the TRN will cause major disturbances to the development and the functioning of the prefrontal cortex (PFC) and the MD. Rat pups at P4 were randomized in three groups: electrolytic lesion of TRN, TRN-sham-lesion group, and the classical control group. Seven weeks later, all rats were tested with several behavioral and cognitive paradigms, and then perfused for histological and immunohistochemical studies. Results showed that TRN lesion rats exhibited reduced spontaneous activity, high level of anxiety, learning and recognition memory impairments. Besides the behavioral effects observed after early TRN lesions, our study showed significant cytoarchitectural and functional changes in the cingulate cortex, the dorsolateral and prelimbic subdivisions of the PFC, as well as in the MD. The assessment of the basal levels of neuronal activity revealed a significant reduction of the basal expression of C-Fos levels in the PFC. These experiments, which are the first to highlight the effects of early TRN lesions, provided evidence that early damage of the anterior part of the TRN leads to alterations that may control the development of the thalamocortical-corticothalamic pathways.

Keywords: behavior; lesion; mediodorsal thalamus; prefrontal cortex; thalamic reticular nucleus.

MeSH terms

  • Animals
  • Anxiety / physiopathology*
  • Learning / physiology*
  • Male
  • Neural Pathways / physiology
  • Neurons / physiology
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / pathology
  • Rats, Sprague-Dawley
  • Recognition, Psychology / physiology*
  • Thalamic Nuclei / metabolism*
  • Thalamic Nuclei / pathology