Electrophysiology of Kisspeptin Neurons - Kisspeptin Signaling in Reproductive Biology - page 346

Fig. 16.4 Bath-applied NKB induces persistent tonic or bursting fi ring activity in KNDy-GFP
neurons. ( a ) Bath-applied NKB (15 min) depolarized a quiescent ARC-KNDy neuron and pro-
duced sustained tonic fi ring activity with little evidence of desensitization. ( b ) In another cell,
NKB applied for 35 min produced persistent bursting activity without any apparent
desensitization
receptors into the cell membrane such that the fi ring response of the ARC-KNDy
cell to NKB is not compromised by gonadectomy in the male. These fi ndings are
consistent with the robust increase in gonadotropin secretion observed following
NKB infusions in intact male mice and castrated adult male monkeys [ 2 , 34 ].
However, in female mice, the NKB effect on gonadotropin secretion is modulated by
sex steroids [ 5 , 35 ]; whether this refl ects a sex difference remains to be determined
and awaits electrophysiology studies on NKB effects in the female under different
sex steroid environments.
Consistent with the non-desensitizing nature of the NKB response to repeated
applications described above, prolonged bath applications of NKB for 15-35 min
produce persistent tonic or burst fi ring activity (Fig. 16.4a, b ). NKB activation of
ARC-KNDy neurons is attenuated by the NK3 receptor antagonist, SB222200
(Fig. 16.5a, b ), and senktide, an NK3R agonist, activates KNDy neurons (Fig. 16.5c ),
indicating a role for NK3 receptors.
In vivo, in the ovariectomized goat, intracerebroventricular infusions of NKB
induce multiunit volleys in the vicinity of ARC-KNDY cells, and dynorphin, which
is also co-localized in KNDy neurons, inhibits multiunit activity. Our in vitro data
suggests that the NKB effect may have occurred via an NKB-induced depolariza-
tion of ARC-KNDy cells [ 4 ]. Further in vitro studies will be required to determine
the specifi c sites of action of dynorphin.
Leptin, an adiposity signal from the fat cells, acts on brain neurons via the leptin
receptor (LepRb) to communicate the availability of energy reserves. Leptin also
regulates puberty, fertility, and sex behaviors [ 36 - 38 ]; mutations in leptin signaling
pathways result in reproductive defi cits [ 39 ]. Leptin can reverse hypogonadotropic
hypogonadism associated with reduced body fat [ 40 - 43 ], and leptin is a potential