Age-dependent shift in spontaneous excitation-inhibition balance of infralimbic prefrontal layer II/III neurons is accelerated by early life stress, independent of forebrain mineralocorticoid receptor expression

Neuropharmacology. 2020 Dec 1;180:108294. doi: 10.1016/j.neuropharm.2020.108294. Epub 2020 Sep 1.


In this study we tested the hypothesis i) that age-dependent shifts in the excitation-inhibition balance of prefrontal neurons are accelerated by early life stress, a risk factor for the etiology of many psychiatric disorders; and if so, ii) that this process is exacerbated by genetic forebrain-specific downregulation of the mineralocorticoid receptor, a receptor that was earlier found to be a protective factor for negative effects of early life stress in both rodents and humans. In agreement with the literature, an age-dependent downregulation of the excitation-inhibition balance was found both with regard to spontaneous and evoked synaptic currents. The age-dependent shift in spontaneous excitatory relative to inhibitory currents was significantly accelerated by early life stress, but this was not exacerbated by reduction in mineralocorticoid receptor expression. The age-dependent changes in the excitation-inhibition balance were mirrored by similar changes in receptor subunit expression and morphological alterations, particularly in spine density, which could thus potentially contribute to the functional changes. However, none of these parameters displayed acceleration by early life stress, nor depended on mineralocorticoid receptor expression. We conclude that, in agreement with the hypothesis, early life stress accelerates the developmental shift of the excitation-inhibition balance but, contrary to expectation, there is no evidence for a putative protective role of the mineralocorticoid receptor in this system. In view of the modest effect of early life stress on the excitation-inhibition balance, alternative mechanisms potentially underlying the development of psychiatric disorders should be further explored.

Keywords: Early life stress; Electrophysiology; GABA; Gene expression; Glutamate; Mineralocorticoid receptor; Morphology; Prefrontal cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Excitatory Postsynaptic Potentials / physiology*
  • Female
  • Gene Expression
  • Inhibitory Postsynaptic Potentials / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / metabolism
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / pathology
  • Prosencephalon / metabolism*
  • Prosencephalon / pathology
  • Receptors, Mineralocorticoid / biosynthesis*
  • Receptors, Mineralocorticoid / genetics
  • Stress, Psychological / metabolism*
  • Stress, Psychological / pathology
  • Stress, Psychological / prevention & control


  • Receptors, Mineralocorticoid