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Mol Psychiatry. 2019 Nov 19. doi: 10.1038/s41380-019-0598-7. [Epub ahead of print]

Novel role for mineralocorticoid receptors in control of a neuronal phenotype.

Author information

1
Synaptic and Developmental Plasticity Group, Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC, 27709, USA.
2
Molecular and Systems Pharmacology Graduate Program, Emory University, Atlanta, GA, USA.
3
Neuroscience Graduate Program, Georgia State University, Atlanta, GA, USA.
4
Center for Neurobiology Research, Fralin Biomedical Research Institute, Virginia Tech Carilion, Roanoke, VA, USA.
5
Synaptic and Developmental Plasticity Group, Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, 111 T.W. Alexander Drive, Research Triangle Park, NC, 27709, USA. dudek@niehs.nih.gov.

Abstract

Mineralocorticoid receptors (MRs) in the brain play a role in learning and memory, neuronal differentiation, and regulation of the stress response. Within the hippocampus, the highest expression of MRs is in area CA2. CA2 pyramidal neurons have a distinct molecular makeup resulting in a plasticity-resistant phenotype, distinguishing them from neurons in CA1 and CA3. Thus, we asked whether MRs regulate CA2 neuron properties and CA2-related behaviors. Using three conditional knockout methods at different stages of development, we found a striking decrease in multiple molecular markers for CA2, an effect mimicked by chronic antagonism of MRs. Furthermore, embryonic deletion of MRs disrupted afferent inputs to CA2 and enabled synaptic potentiation of the normally LTP-resistant synaptic currents in CA2. We also found that CA2-targeted MR knockout was sufficient to disrupt social behavior and alter behavioral responses to novelty. Altogether, these results demonstrate an unappreciated role for MRs in controlling CA2 pyramidal cell identity and in facilitating CA2-dependent behaviors.

PMID:
31745235
DOI:
10.1038/s41380-019-0598-7

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