Abstract

In most species, survival relies on the hypothalamic control of endocrine axes that regulate critical functions such as reproduction, growth, and metabolism. For decades, the complexity and inaccessibility of the hypothalamic–pituitary axis has prevented researchers from elucidating the relationship between the activity of endocrine hypothalamic neurons and pituitary hormone secretion. Indeed, the study of central control of endocrine function has been largely dominated by ‘traditional’ techniques that consist of studying in vitro or ex vivo isolated cell types without taking into account the complexity of regulatory mechanisms at the level of the brain, pituitary and periphery. Nowadays, by exploiting modern neuronal transfection and imaging techniques, it is possible to study hypothalamic neuron activity in situ, in real time, and in conscious animals. Deep-brain imaging of calcium activity can be performed through gradient-index lenses that are chronically implanted and offer a ‘window into the brain’ to image multiple neurons at single-cell resolution. With this review, we aim to highlight deep-brain imaging techniques that enable the study of neuroendocrine neurons in awake animals whilst maintaining the integrity of regulatory loops between the brain, pituitary and peripheral glands. Furthermore, to assist researchers in setting up these techniques, we discuss the equipment required and include a practical step-by-step guide to performing these deep-brain imaging studies.

Highlights

  • Neuroendocrinologists have worked towards characterising the central regulation of endocrine axes that ensure critical functions such as reproduction, growth, and metabolism

  • Overall, being able to study the activity of specific hypothalamic neurons in awake animals and in real time offers an incredible and invaluable opportunity to broaden our understanding of how the brain controls endocrine function

  • It gives us the opportunity to study why endocrine functions become disrupted in pathophysiological conditions, and how these changes may lead to the development or even protection from pathological consequences

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Summary

Introduction

Neuroendocrinologists have worked towards characterising the central regulation of endocrine axes that ensure critical functions such as reproduction, growth, and metabolism. While research questions have for many years focused firmly on the neural control of the pituitary gland, the neuroendocrinology field has grown wider and includes studying the effect of centrally produced hormones on various brain areas, as well as the role of several peripherally born peptides that affect neuroendocrine systems controlling metabolism. An unavoidable feature of all neuroendocrine systems is that they generate rhythms and rely on these rhythms to function optimally. These hormone oscillations dynamically regulate gene transcription and synaptic transmission, and changes in these oscillations are observed in a variety of (patho)physiological states (Le Tissier et al 2017).

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