Corticosterone mediated functional and structural plasticity in corticotropin-releasing hormone neurons

• Published in: Neuropharmacology 2019-08, Vol.154, p.79-86
• Main Authors: Bittar, Thibault P., Nair, Betina B., Kim, Joon S., Chandrasekera, Dhananjie, Sherrington, Aidan, Iremonger, Karl J.
• Format: Article
• Language: English
• Subjects: Animals; Chronic stress; Corticosterone; Corticosterone - administration & dosage; Corticosterone - blood; Corticotropin-releasing hormone; Corticotropin-Releasing Hormone - blood; Dendrite; Dendritic Spines - drug effects; Dendritic Spines - pathology; Dendritic Spines - physiology; Excitability; Intrinsic plasticity; Mice; Mice, Transgenic; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Neurons - drug effects; Neurons - pathology; Neurons - physiology; Paraventricular nucleus; Spine
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2019.02.017

Corticosteroid stress hormones drive a multitude of adaptations in the brain. Hypothalamic corticotropin-releasing hormone (CRH) neurons control the circulating levels of corticosteroid stress hormones in the body and are themselves highly sensitive to corticosteroids. CRH neurons have been shown to undergo various adaptions in response to acute stress hormone elevations. However, their structural and physiological changes under chronically elevated corticosterone are less clear. To address this, we determined the structural and functional changes in CRH neurons in the paraventricular nucleus of the hypothalamus following 14 days of corticosterone treatment. We find that prolonged corticosterone elevation reduces CRH neuron intrinsic excitability as measured by summation of subthreshold postsynaptic depolarisations and spiking output. We find that under normal conditions, CRH neurons have a relatively compact and simple dendritic arbor, with a low density of somatic and dendritic spines. Interestingly, the axon originated from a proximal dendrite close to the soma in approximately half of the CRH neurons reconstructed. While prolonged elevation in corticosterone levels did not result in any changes to gross dendritic morphology, it induced a significant reduction in both somatic and dendritic spine density. Together these data reveal the morphological features of hypothalamic CRH neurons and highlight their capacity to undergo functional and morphological plasticity in response to chronic corticosterone elevations. This article is part of the Special Issue entitled ‘Hypothalamic Control of Homeostasis’. •CRH neurons have a simple dendritic morphology with a low density of somatic and dendritic spines.•Following prolonged elevations in corticosterone, CRH neurons show a reduction in intrinsic excitability.•Prolonged corticosterone elevations lead to a reduction in dendritic spines but no change in gross dendritic morphology.