Electrophysiology of Kisspeptin Neurons - Kisspeptin Signaling in Reproductive Biology - page 349

Neurotransmitter and Neuropeptide Modulation of RP3V
Kisspeptin Neurons
Similar to the ARC-KNDy cells, RP3V-Kiss1 neurons are strongly activated by
glutamate and inhibited by GABA. Antagonist data also suggests that, at least
in vitro, RP3V-Kiss1 neuron activity is not under either an excitatory or inhibitory
tone due to endogenously released glutamate or GABA [ 55 ].
Since both kisspeptin expression and neuronal activity (measured using c-fos) in
RP3V-Kiss1 neurons fl uctuate on a circadian basis [ 16 ], there is considerable inter-
est in whether the activity of RP3V-Kiss1 neurons is modulated by neuropeptides
associated with circadian signaling. Interestingly, the two classical transmitters
released from the suprachiasmatic nucleus, vasopressin and vasoactive intestinal
peptide (VIP), have thus far been shown to have no direct effect on the activity of
RP3V-Kiss1 neurons [ 55 ]. If future studies corroborate these fi ndings, indirect
mechanisms will need to be investigated to comprehend mechanisms underlying
circadian linking to RP3V kisspeptin neurons.
RFRP-3, another neuropeptide implicated in reproduction, has no effect on RP3V-
Kiss1 neurons [ 55 ]. Similar to ARC-KNDy neurons, kisspeptin also does not affect
RP3V-Kiss1 neurons, suggesting lack of autoregulation via released kisspeptin.
Conclusions
Kisspeptin cells of the arcuate nucleus and the RP3V region fi re action potentials in
a tonic, irregular, or bursting pattern in vitro in brain slices, and are inhibited by
GABA and activated by glutamate. The membrane properties of ARC-KNDy neu-
rons are strongly modulated by sex steroids. Similarly, the fi ring activity and pattern
of RP3V-Kiss1 neurons is estrus cycle-dependent, but is not directly regulated by
the circadian cycle peptides, VIP, and vasopressin. NKB and NK3R agonists are
potent activators of KNDy neurons, providing a mechanistic interpretation of how
NKB sustains normal reproductive functions. Leptin activates ARC-KNDy neuron,
supporting their role in linking metabolism to reproduction.
References
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