ESPE Abstracts (2015) 84 NP1.2

Optogenetic Control of Neuroendocrine Hormone Secretion

Allan Herbisona,b

aUniversity of Otago, Dunedin, New Zealand; bCentre for Neuroendocrinology, Dunedin, New Zealand

Optogenetics represents a powerful new approach to modulate the activity of excitable cells in the body. Based upon the ability of specific wavelengths of light to activate newly discovered and engineered opsin-based receptors, optogenetics can be used to control the activity of cells with very high temporal resolution. Opsin-based receptors, most often channelrhodopsin (ChR), need to be expressed selectively in the cell type under investigation. This is achieved by generating genetically-modified rodent models in which ChR is expressed only in a specific cell phenotype or by using viruses to deliver Cre-dependent ChRs to genetically manipulated Cre-driver rodent lines.

In the field of experimental endocrinology, optogenetics has been extremely useful for investigating the neuroendocrine control of pituitary hormone secretion. For example, mice and rats with ChR expressed only in the GnRH neurons have been used to examine how these neurons generate pulsatile patterns of LH. By inserting optic fibres delivering 470 nm blue light into the brain regions of GnRH-ChR mice that contain the GnRH neuron cell bodies or their distal processes, it has been possible to remotely control the electrical activity of groups of GnRH neurons and determine the patterns of firing required to generate a pulse of gonadotropin (Campos & Herbison, 2014). By expressing ChR in other neuronal phenotypes it has also been possible to explore which cells in the brain innervate the GnRH neurons and are involved in generating their episodic activity. To date the most promising up-stream candidate has been the kisspeptin neurons of the hypothalamic arcuate nucleus.

Optogenetics provides a new research tool enabling the remote, high-fidelity, control of specific neuroendocrine cell populations in vivo and, thereby, an unparalleled means through which investigators can probe the cell networks underlying pituitary hormone secretion.

Campos P & Herbison AE. Optogenetic activation of GnRH neurons reveals minimal requirements for pulsatile luteinizing hormone secretion. PNAS 2014 111 18387–18392.

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