Regulation of corticotropin-releasing hormone neuronal network activity by noradrenergic stress signals.

Noradrenaline is a neurotransmitter released in response to homeostatic challenge and activates the hypothalamic-pituitary-adrenal axis via stimulation of corticotropin-releasing hormone (CRH) neurons. Here we investigated the mechanism through which noradrenaline regulates activity within the CRH neuronal network. Using a combination of in vitro GCaMP6f Ca2+ imaging and electrophysiology, we show that noradrenaline induces a robust increase in excitability in a proportion of CRH neurons with many neurons displaying a bursting mode of activity. Noradrenaline-induced activation required α1 -adrenoceptors and L-type voltage-gated Ca2+ channels, but not GABA/glutamate synaptic transmission or sodium action potentials. Exposure of mice to elevated corticosterone levels was able to suppress noradrenaline-induced activation. These results provide further insight into the mechanisms by which noradrenaline regulates CRH neural network activity and hence stress responses. KEY POINTS: GCaMP6f Ca2+ imaging and on-cell patch-clamp recordings reveal that corticotropin-releasing hormone neurons are activated by noradrenaline with many neurons displaying a bursting mode of activity. Noradrenaline-induced activation requires α1 -adrenoceptors. Noradrenaline-induced Ca2+ elevations persist after blocking GABAA , AMPA, NMDA receptors and voltage-gated Na+ channels. Noradrenaline-induced Ca2+ elevations require L-type voltage-gated Ca2+ channels. Corticosterone suppresses noradrenaline-induced excitation.

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

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'.

Development of an English-language version of a Japanese iPad application to facilitate collaborative goal setting in rehabilitation: a Delphi study and field test.

OBJECTIVE: This study aimed to investigate the content of an English-language version of a Japanese iPad application designed to facilitate shared decision-making around goal setting in rehabilitation: Aid for Decision-making in Occupational Choice-English (ADOC-E). DESIGN: Phase 1: Delphi methods to reach consensus with an international group of expert occupational therapists on the text and images in ADOC-E. Phase 2: Testing correct recognition (unprompted and prompted) of images in ADOC-E by health service users in inpatient rehabilitation and residential care. SETTING: Phase 1: International, online. Phase 2: Three healthcare services in New Zealand-(1) a residential rehabilitation service for traumatic brain injury, (2) a nursing home for frail older adults and (3) an inpatient rehabilitation ward in a public hospital. PARTICIPANTS: Phase 1: Fourteen experienced occupational therapists from New Zealand (4), Australia (4), UK (2) and USA (4). Phase 2: Twenty-four rehabilitation and residential care service users (10 men, 14 women; 20-95 years; Mini-Mental State Exam scores 13-30). RESULTS: Four Delphi rounds were required to reach consensus with the experienced occupational therapists on the content of ADOC-E, ending with 100 items covering daily activities that people do and social roles they participate in. Ninety-five per cent (95/100) of ADOC-E items could each be correctly identified by over 80% of service user participants with either unprompted or prompted recognition. CONCLUSION: While a few of the more abstract concepts in ADOC-E (related to complex social roles) were less likely to be correctly recognised by all participants, the text and images ADOC-E were deemed to be fit for purpose overall and ready for future clinical testing.