Endocrine Abstracts

Survival of most species relies on the fact that small populations of endocrine neurons located in the hypothalamus determine critical functions such as reproduction, growth, and metabolism. These neurons are so finely regulated that their functions have been conserved across evolution; nonetheless, the mechanisms underlying these regulatory features remain hazy. Indeed, research efforts have been hindered by the complexity and inaccessibility of the hypothalamic-pituitary system, and the study of neuroendocrine function has been dominated by techniques that consist of studying in vitro or ex vivo preparations that lack many of the important regulatory mechanisms functioning in vivo at the level of the brain, pituitary and periphery. Nowadays, it is possible to exploit the advantages of neuronal transfection and advanced imaging techniques to study hypothalamic neuron activity in situ, in real time, and in conscious animals. Genetically-encoded calcium indicators have now become widely used for calcium imaging in living organisms. Their always-improving characteristics make them not only an excellent proxy for electrical activity, but also a versatile tool that allows diverse imaging techniques. Deep-brain imaging of calcium activity can be performed through gradient-index lenses that are chronically implanted and permit imaging of multiple neurons at single-cell resolution. Depending on the research question and the imaging quality required, visualisation of the neurons can be carried out in head-fixed configuration using bench-top microscopes, or in freely-moving configuration using miniature head-mounted microscopes. Alternatively, population-level neuronal calcium activity can be recorded in freely-moving animals using fibre photometry; here, an optical fibre delivers excitation light and collects the overall fluorescence of neurons expressing a calcium indicator. Importantly, using any of these techniques, it becomes possible to correlate the impact of neuronal activity on other functions, for example, blood sampling can be performed whilst recording neuronal activity in order to provide a link between the activity of specific hypothalamic neuron and the resulting peripheral hormonal release. Overall, the use of deep-brain imaging techniques in conscious rodents has the potential to broaden our understanding of how the brain controls endocrine function. It also gives us the opportunity to study why endocrine functions become disrupted in pathophysiological conditions, and how these changes may lead to the development of pathological consequences.