Electrophysiology of Kisspeptin Neurons - Kisspeptin Signaling in Reproductive Biology - page 348

Using pSTAT3-immunoreactivity as a marker of a direct response to leptin, Cravo
et al. found that 15% of ARC-KNDy neurons in the diestrus female mouse respond
directly to leptin [ 50 ]. Thus, there is a huge discrepancy in these studies. Caution
should be used to interpret results from STAT3 signaling, as it may not be required
for leptin's regulation of reproduction [ 51 ].
Multiple indirect mechanisms have been evoked to explain leptin's actions on the
reproductive axis. Leptin may act indirectly, via the pre-mammillary nucleus [ 52 , 53 ]
and/or via POMC neurons [ 10 , 54 ]. Louis et al. have demonstrated that hypotha-
lamic neurons located in the striohypothalamic nucleus, preoptic area, and ventral
pre-mammillary nucleus may directly innervate GnRH neurons, and Kiss1 neurons
may be directly innervated by POMC or other ARC neurons expressing leptin
receptors.
In the female guinea pig, direct effects of leptin on arcuate Kiss1 expressing
cells have been described in a signifi cant majority of neurons, using the electro-
physiological approach. These effects are mediated via activation of a nonselective
cationic conductance and are blocked by the TRPC channel blocker, 2-APB, as
well as by inhibitors of Jak, PI3K, and PLC Υ , demonstrating coupling to the JAK-

PI3K-PLC pathway [ 18 ]. Further electrophysiological studies will be required to

determine if mouse ARC-KNDY neurons also respond directly to leptin. In conclu-
sion, multiple indirect and direct mechanisms may convey the effects of leptin on
reproductive parameters.

Υ

Kisspeptin Neurons of the RP3V

Intrinsic Properties

The sexually dimorphic, estrogen receptor- -expressing kisspeptin neurons of the

RP3V are considered integral to the control of preovulatory surge mechanisms [ 12 - 14 ].
The membrane properties of RP3V neurons in female mice were fi rst reported in
2010 using labor-intensive double-labeling studies [ 55 ]. Similar to KNDy neurons
of the arcuate nucleus, RP3V-Kiss1 neurons fi re action potentials in irregular, tonic,
or burst fi ring patterns. Published data suggests that a vast majority of RP3V-Kiss1
spontaneously discharge action potentials in brain slices, irrespective of the phase
of the estrus cycle [ 55 ]. However, the fi ring rate and the pattern of fi ring in RP3V-
Kiss1 neurons may fl uctuate with the phase of the cycle. Thus, RP3V-Kiss1 neurons
fi re at lower rates in brain slices prepared from diestrus vs. proestrus/estrus mice,
and their fi ring pattern switches from predominantly tonic to irregular on transition
from diestrus to proestrus. In general, the spontaneous fi ring rate of RP3V-Kiss1
neurons ranges from 0.2 to 7.7 Hz in brain slices, and is higher than that of the
neighboring non-Kiss1 cells. Future studies will be required to determine if other
membrane properties, such as resting membrane potential and membrane resis-
tance, fl uctuate with the estrus cycle, and how changes in these properties alter the
receptivity of RP3V neurons to afferent inputs.

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