Abstract
In the brain, membrane associated nongenomic steroid receptors can induce fast-acting responses to ion conductance and second messenger systems of neurons. Emerging data suggest that membrane associated glucocorticoid and mineralocorticoid receptors may directly regulate synaptic excitability during times of stress when adrenal hormones are elevated. As the key neuron signaling interface, the synapse is involved in learning and memory, including traumatic memories during times of stress. The lateral amygdala is a key site for synaptic plasticity underlying conditioned fear, which can both trigger and be coincident with the stress response. A large body of electrophysiological data shows rapid regulation of neuronal excitability by steroid hormone receptors. Despite the importance of these receptors, to date, only the glucocorticoid receptor has been anatomically localized to the membrane. We investigated the subcellular sites of mineralocorticoid receptors in the lateral amygdala of the Sprague-Dawley rat. Immunoblot analysis revealed the presence of mineralocorticoid receptors in the amygdala. Using electron microscopy, we found mineralocorticoid receptors expressed at both nuclear including: glutamatergic and GABAergic neurons and extra nuclear sites including: presynaptic terminals, neuronal dendrites, and dendritic spines. Importantly we also observed mineralocorticoid receptors at postsynaptic membrane densities of excitatory synapses. These data provide direct anatomical evidence supporting the concept that, at some synapses, synaptic transmission is regulated by mineralocorticoid receptors. Thus part of the stress signaling response in the brain is a direct modulation of the synapse itself by adrenal steroids.
Highlights
The amygdala, the lateral nucleus, (LA) is established as a site for the acquisition and storage of conditioned fear memory and a trigger of the stress response [1,2,3,4,5]
Western blot immunoassay was used to determine the presence of MR in amygdala nuclei
This study provides the first anatomical evidence for the expression of MR in LA synapses
Summary
The amygdala, the lateral nucleus, (LA) is established as a site for the acquisition and storage of conditioned fear memory and a trigger of the stress response [1,2,3,4,5]. The expression of conditioned fear includes amygdala dependent activation of the hypothalamic-pituitary-adrenal (HPA) axis. The HPA-axis increases blood concentration of corticosterone in rodents, which in turn feeds back to the brain including the amygdala where it binds to both mineralocorticoid (MRs) and glucocorticoid receptors (GRs) [6,7,8]. Cytosolic MR and GR translocate to the nucleus upon activation, which results in changes in gene transcription [11,12,13]. Recent evidence suggests the LA likely contains signaling mechanisms that include both classic nuclear MR and GR signaling as well as direct signaling from the synapse via membrane receptors mechanisms [7,8,14,15], which regulates the fear response and influence fear related behaviors [16,17,18,19,20,21,22]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
