Electrophysiology of Kisspeptin Neurons - Kisspeptin Signaling in Reproductive Biology - page 341

The fi rst evidence for pulsatility in ARC-KNDy neurons came from in vivo goat
studies, which observed repetitive electrical burst activity in the vicinity of putative
ARC-KNDy neurons in the medial basal hypothalamus, but not when electrode
placements were distant from where ARC-KNDy neurons would reside [ 17 ].
Moreover, the recorded burst activity synchronized with discrete pulses of LH and
was reduced by gonadal steroid treatments [ 4 ]. Additionally, the burst activity con-
tinued unabated following systemic infusions of kisspeptin, which enhance GnRH
and LH secretion, suggesting that the bursting neurons are located upstream of
GnRH neurons [ 17 ].
More recently, in vitro studies on identifi ed kisspeptin neurons, enabled by the
development of transgenic mouse models that express GFP selectively in kisspeptin
cells, have probed for evidence of pulsatility. Initial studies show that about 50% of
ARC-KNDy-GFP neurons are quiescent in vitro, in brain slices of adult ovariecto-
mized female mice, while the remaining neurons fi re action potentials in a tonic or
an irregular manner [ 1 ]. Importantly, ARC-KNDy neurons have the capability to
fi re action potentials in bursts, as they express the requisite underlying channels that
permit burst fi ring. Thus, kisspeptin neurons in both the guinea pig [ 18 ] and the
mouse exhibit the hyperpolarization-activated cyclic nucleotide-gated mixed cat-
ionic current (H current) and the T-type calcium current. These currents are well
known to underlie endogenous burst fi ring in several CNS neurons. The glutamate
agonist, NMDA, also triggers burst fi ring in KNDy cells (see Sect. Neurotransmitter
and Neuropeptide Modulation of ARC-KNDy Neurons ).
Similar to the ovariectomized female, our studies show that ARC-KNDy neu-
rons from male mice also exhibit tonic, irregular, and bursting fi ring patterns
(Fig. 16.1a ). Quiescent cells can acquire any of the three fi ring patterns upon depo-
larization. Currently, it is unclear whether ARC-KNDy cells can switch their fi ring
pattern from tonic to irregular/bursting or vice versa. We have also found that sex
steroids exert a dramatic infl uence on the membrane properties of ARC-KNDy
neurons, which is consistent with the presence of sex steroid receptors in these
neurons [ 7 , 19 ]. Thus, ARC-KNDy neurons from male GDX mice are more likely
to be quiescent in their resting state in vitro; only 10% of KNDy-GDX neurons fi re
spontaneously, whereas 40% of KNDY neurons from gonadally intact mice fi re
spontaneously in brain slices (Fig. 16.1b ). The mean resting membrane potential of
the quiescent neurons in GDX neurons is similar to that of quiescent neurons in the
intact group (Fig. 16.1c ). However, KNDY neurons from GDX male mice have
lower membrane resistances, about half that of KNDy neurons from intact adult
mice (Fig. 16.1d ), and are less excitable—requiring double the amounts of current
to elicit an action potential (Fig. 16.1e ). The gonadectomy-induced changes noted
above take several days to develop after castration ( not shown ), and thus, are
unlikely to be due to an acute withdrawal of sex steroids in the excised slice prepa-
ration. Nevertheless, it would be important to examine Kiss1 neuron properties
under controlled sex steroid levels in brain slices. It should also be stated that the
above studies on ARC-KNDy neurons were performed using the coronal slice
preparation. Since the membrane properties of a neuron are dependent on its den-
dritic and axonal arbor, properties of Kiss1 neurons should also be examined in