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of recorded neurons. Earlier studies utilized labor-intensive double-labeling studies
for identifi cation of recorded neurons. The recent development of transgenic kiss-
peptin mouse models in which reporter genes are expressed have enabled a direct
examination of the electrophysiological and neuropharmacological characteristics
of kisspeptin neurons [ 1 , 2 ].
Although still in their infancy, electrophysiological studies are providing signifi -
cant insights into how kisspeptin neurons might control reproductive circuits, medi-
ate sex steroid feedback, and link metabolic to reproductive pathways. In this
chapter, we describe the advances made in understanding the cellular, molecular,
and morphological properties of kisspeptin neurons located in the arcuate nucleus
(ARC-KNDy neurons) and in the sexually dimorphic anteroventral periventricular
and periventricular preoptic nuclei (RP3V-Kiss1 neurons), primarily using in vitro
electrophysiological approaches in guinea pig and mice.
ARC-KNDy neurons co-localize kisspeptin, neurokinin B (NKB), and dynor-
phin [ 3 - 5 ]. These neurons are equally well represented in adults of both sexes [ 6 ]
and have been implicated in mediating sex steroid-dependent negative feedback [ 7 ].
KNDy neurons also express neurokinin 3 receptor (Tac3r) mRNA [ 5 ] and have been
suggested to mediate the effects of neurokinin B on reproduction. KNDy cells may
also play a role in the metabolic regulation of reproduction, perhaps in mediating
the reproductive effects of leptin [ 8 - 11 ].
RP3V-Kiss1 neurons are sparse in males but prevalent in females [ 6 ], and may
participate in the female-specifi c preovulatory GnRH/LH surge via sex steroid-
mediated positive feedback mechanisms [ 7 , 12 - 14 ]. The transcriptional activity of
RP3V-Kiss1 neurons has been reported to be dependent on circadian signaling
[ 15 , 16 ], which may relate to the circadian-timed onset of the LH surge. The elec-
trophysiological studies described below have, amongst other goals, aimed to clar-
ify the role of the above two kisspeptin neuronal subpopulations in mediating sex
steroid feedback and in linking reproductive circuits to metabolic and circadian
pathways.
Kisspeptin Neurons of the Arcuate Nucleus
Membrane Properties and Modulation by Sex Steroids
A study of the intrinsic membrane properties of neurons enables an understanding
of the fi ring patterns and rhythms a cell may be capable of generating. This knowl-
edge is especially critical for the neuroendocrine reproductive system, as pulsatile
secretion of GnRH is essential for sustaining normal gonadotropin secretion and
reproductive fertility in mammals of both sexes. Accumulating evidence suggests
that this pulsatility originates in kisspeptin neurons of the arcuate nucleus, which
provide a rhythmic drive to the GnRH neurons that culminates in pulsatile gonado-
tropin secretion.
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