Functional and anatomical characterization of synaptic connections of kisspeptin neurons

Eyuboğlu, S. (2018). Functional and anatomical characterization of Kisspeptin Neuron's Synaptic Connections İstanbul University, Institute of Health Science, Department of Physiology, Ph.D. thesis, İstanbul. Kisspeptin is defined as a metastatic suppressor gene in human metastatic melanoma cancer cells. Furthermore, it is known that Kisspeptin has important roles in regulating gonadotropin-releasing hormone secretion, onset puberty and maintaining reproductive function by stimulating Kiss1r receptors on GnRH neurons. Also, Kiss1r mutations cause reproductive system diseases such as hypogonadotropic gonadism. Yet, the neuronal circuits in mammals that depend on kisspeptins which thought to have many physiological functions remain unidentified. In this study, the projections between the kiss1 neurons and other brain regions were investigated by specifically targeting the two major kiss1 neuron populations of the hypothalamic area, the arcuate nucleus (ARC) and the anteroventral periventricular (AVPV) nucleus. In this experiments conducted with Cre transgenic mice, neuroanatomical projections have been shown for the first time using combine virus-based systems for imaging coexpression of synaptophysin and kiss1. Accordingly, ARC kiss1 neuron fibers with presynaptic terminals have been demonstrated in both female and male adult mice in several brain regions primarily paraventricular nucleus (PVN), medial preoptic area (MPO), AVPV. In addition, AVPV kiss1 neurons projected to lateral septum, ARC, MPO, and its extending fibers have been found in many locations such as the periventricular nucleus, medial septum, Broca's diagonal band (DBB). Through the electrophysiological recordings from selected brain regions in the established optogenetic experiments, the projections of ARC kiss1 neurons were also functionally examined. Changes in the frequency of spontaneous neuronal firing of postsynaptic neurons in the PVN, MPO, contralateral ARC regions after optogenetic stimulation were observed, and these regions were found to have neurons receiving the signal from ARC kiss1 neurons. Thus, important findings have been obtained that kiss1 neurons may have different functional associations with other brain regions. Key Words: Arcuate nucleus, Electrophysiology, Kisspeptin, Optogenetic, Synaptophysin