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
| Autor: | Nelleke van der Weerd, Henk Karst, R. Angela Sarabdjitsingh, Ruth Damsteegt, Marian Joëls, Eline Feenstra |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Mineralocorticoid receptor BEHAVIORAL FLEXIBILITY CHILDHOOD Gene Expression GABA Mice 0302 clinical medicine SYNAPTIC PLASTICITY BRAIN Prefrontal cortex Receptor Mice Knockout Neurons Glutamate receptor Age Factors Electrophysiology Female Glutamate Morphology medicine.medical_specialty CORTEX Prefrontal Cortex Biology Inhibitory postsynaptic potential MATURATION 03 medical and health sciences Cellular and Molecular Neuroscience Prosencephalon Downregulation and upregulation Internal medicine medicine Animals Pharmacology CA1 PYRAMIDAL NEURONS Excitatory Postsynaptic Potentials Early life stress INTRACELLULAR CHLORIDE Mice Inbred C57BL 030104 developmental biology Endocrinology Receptors Mineralocorticoid Animals Newborn Inhibitory Postsynaptic Potentials Synaptic plasticity Forebrain MATERNAL-CARE 030217 neurology & neurosurgery Stress Psychological |
| Zdroj: | Neuropharmacology, 180:108294, 1-12. PERGAMON-ELSEVIER SCIENCE LTD |
| ISSN: | 1873-7064 0028-3908 |
| Popis: | In this study we tested the hypothesis i) that age-dependent shifts in the excitation-inhibition balance of pre-frontal 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. |
| Databáze: | OpenAIRE |
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