Biology Reference
In-Depth Information
Activation of Oxytocin Neurons by Central Kisspeptin
in Pregnancy and Lactation
Several electrophysiology studies have shown that kisspeptin directly excites various
neuronal populations: GnRH neurons, arcuate nucleus neurons, pro- opiomelanocortin
neurons and hippocampal neurons are all excited by direct application of kisspeptin
to brain slices [
65
-
68
]. So, we administered icv kisspeptin-10 in the expectation that
we would localise the site of action of IV kisspeptin-10 to the brain. However, to our
surprise, we did not fi nd any effect of icv kisspeptin on the fi ring rate of oxytocin
neurons in non-pregnant rats. In fact, in marked contrast to the robust and repeatable
excitation following IV kisspeptin, there was no change in fi ring rate following icv
injection at 2
L volume) in any oxytocin neuron tested
(Fig.
10.3
), even in those neurons that were excited by IV kisspeptin-10. The higher
dose of icv kisspeptin-10 that we used (40
μ
g or at 40
μ
g (both in a 2
μ
g) has been published as inducing a very
robust response in the GnRH system to markedly increase circulating luteinising
hormone levels [
69
], so it is very unlikely that the failure of icv kisspeptin-10 to
excite oxytocin neurons in non-pregnant rats was due to a failure to deliver suffi cient
kisspeptin. The unexpected lack of response of oxytocin neurons to icv kiss-
peptin-10, combined with a robust response to IV kisspeptin, suggests that
kisspeptin-10 might not cross the blood brain barrier to act directly on oxytocin
neurons, or on Kiss1r that might be expressed by any central inputs to the SON.
Consistent with our observed lack of effect of icv kisspeptin-10 on oxytocin neurons
in non-pregnant rats, a recent mapping study has shown the presence of only a few
kisspeptin fi bres in the locality of the SON and it is not known whether they termi-
nate in or form synapses in the area [
70
]. Additionally, there is no clear indication as
to whether the Kiss1r is expressed in the SON [
71
].
Notwithstanding the lack of effect of icv kisspeptin on oxytocin neurons in non-
pregnant rats, we continued to administer icv kisspeptin during our more recent stud-
ies into the effects of IV kisspeptin in pregnancy and lactation. The preliminary data
that we have generated make the lack of effect of icv kisspeptin on oxytocin neurons
in non-pregnant animals even more intriguing because our unpublished observations
suggest that a central kisspeptin excitation of oxytocin neurons might emerge over the
course of pregnancy in rats and that this is sustained during lactation.
In our latest experiments, we made in vivo extracellular single-unit recordings
from oxytocin neurons in rats on different days of pregnancy (day 15-21). As
described above, the response of oxytocin neurons to peripheral kisspeptin-10 was
maintained throughout pregnancy, with IV injections of kisspeptin-10 continuing to
cause a short (~5 min) increase in the fi ring rate of oxytocin neurons recorded from
pregnant rats. This excitation was indistinguishable from the response seen in non-
pregnant rats (Fig.
10.2
), with the increase in fi ring rate following the peripheral
injection occurring within 30 s and returning to basal levels 5-10 min later.
By contrast to the consistent responses to IV kisspeptin, there appears to be a
marked change in the response of oxytocin neurons to icv kisspeptin-10 that arises
over the course of pregnancy. In all oxytocin neurons recorded from animals on day
μ
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