RT Journal Article
SR Electronic
T1 Arcuate and Preoptic Kisspeptin neurons exhibit differential projections to hypothalamic nuclei and exert opposite postsynaptic effects on hypothalamic paraventricular and dorsomedial nuclei in the female mouse
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0093-21.2021
DO 10.1523/ENEURO.0093-21.2021
A1 Todd L. Stincic
A1 Jian Qiu
A1 Ashley M. Connors
A1 Martin J. Kelly
A1 Oline K. Rønnekleiv
YR 2021
UL http://www.eneuro.org/content/early/2021/07/19/ENEURO.0093-21.2021.abstract
AB Kisspeptin (Kiss1) neurons provide indispensable excitatory input to GnRH neurons, which is important for the coordinated release of gonadotropins, estrous cyclicity and ovulation. However, Kiss1 neurons also send projections to many other brain regions within and outside the hypothalamus. Two different populations of Kiss1 neurons, one in the arcuate nucleus (Kiss1ARH) and another in the anteroventral periventricular and periventricular nucleus (Kiss1AVPV/PeN) of the hypothalamus are differentially regulated by ovarian steroids, and are believed to form direct contacts with GnRH neurons as well as other neurons. To investigate the projection fields from Kiss1AVPV/PeN and Kiss1ARH neurons in female mice, we used anterograde projection analysis, and channelrhodopsin-assisted circuit mapping (CRACM) to explore their functional input to select target neurons within the paraventricular (PVH) and dorsomedial (DMH) hypothalamus, key pre-autonomic nuclei. Cre-dependent viral (AAV1-DIO-ChR2 mCherry) vectors were injected into the brain to label the two Kiss1 neuronal populations. Immunocytochemistry for mCherry and neuropeptides combined with confocal microscopy was used to determine the projection-fields of both Kiss1 neuronal groups. Whole-cell electrophysiology and optogenetics was used to elucidate the functional input to the PVH and DMH. Our analysis revealed many common, but also several clearly separate projection fields between the two different populations of Kiss1 neurons. In addition, optogenetic stimulation of Kiss1 projections to PVH prodynorphin, Vglut2 and DMH CART-expressing neurons, revealed excitatory glutamatergic input from Kiss1ARH neurons and inhibitory GABAergic input from Kiss1AVPV/PeN neurons. Therefore, these steroid-sensitive Kiss1 neuronal groups can differentially control the excitability of target neurons to coordinate autonomic functions with reproduction.Significance StatementHypothalamic kisspeptin (Kiss1) neurons are the most gonadal steroid-sensitive neurons in the brain, and its principle neurotransmitter kisspeptin is essential for sexual development and reproduction through direct excitation of GnRH neurons. Kiss1 neurons also co-express either the classical neurotransmitters GABA, which we document is released only by Kiss1AVPV/PeN neurons or glutamate, which is released by Kiss1ARH neurons. Consequently, Kiss1AVPV/PeN neurons have direct inhibitory and Kiss1ARH neurons direct excitatory actions onto PVH and DMH neurons known to controlling food intake and energy expenditure, respectively. Therefore, we have found that Kiss1 neurons have a significant input to “pre-autonomic” neurons known to regulate multiple homeostatic functions, which would help coordinate reproduction with these other functions that are vital for survival of the species.