Electrophysiology of Kisspeptin Neurons - Kisspeptin Signaling in Reproductive Biology - page 344

Fig. 16.2 Gonadectomy induces somatic hypertrophy in KNDy-GFP neurons. ( a ) Shows a
neurobiotin-fi lled ARC-KNDy neuron from an adult-GDX male. Note the bipolar shape and the
long process. ( b ) Shows neurobiotin-fi lled ARC-KNDy cell somas from intact and GDX male
mice. Note the larger size of the two somas from the GDX group ( right column ). ( c ) Bar chart
summarizes the strikingly larger cross-sectional area of KNDY-GDX neurons
Neurotransmitter and Neuropeptide Modulation
of ARC-KNDy Neurons
Neuropharmacological studies conducted thus far show that the activity of ARC-KNDy
neurons is strongly modulated by amino acid neurotransmitters. The excitatory gluta-
mate receptor agonist, NMDA, reliably induces membrane oscillations in both guinea
pig and female mouse KNDy neurons [ 1 , 18 ]. These oscillations are mediated via a
direct action of NMDA on ionotropic receptors in ARC-KNDy cells, as they persist
after blockade of synaptic transmission. The inhibitory neurotransmitter, GABA, has
an opposing effect—it strongly inhibits ARC-KNDy neurons [ 1 , 18 ]. Inhibitory inputs
to ARC-KNDY cells could potentially provide a feedback circuit for sustaining burst
fi ring in ARC-KNDy neurons. Whether GABA or glutamate antagonists alter the fi ring
activity of ARC-KNDy neurons is not yet known. Future studies will also be required
to determine if the effects of NMDA and GABA on ARC-KNDy neurons are age- or
sex-dependent.
We have recently shown that the activity of ARC-KNDy neurons is strongly mod-
ulated by the neuropeptide, neurokinin B (NKB) [ 2 ], that is contained within the
ARC-KNDy neurons. In contrast, our preliminary data suggests a lack of effect of
kisspeptin on ARC-KNDY neurons ( not shown ). Whether the NKB input to ARC-
KNDY neurons originates from ARC-KNDy neurons themselves remains unknown.
Brief applications of NKB (15 s) depolarize ARC-KNDY neurons and may elicit
volleys of action potentials in a tonic or burst pattern with varied response durations
(Fig. 16.3a, b , h). The NKB effect shows little evidence of desensitization on repeated
applications (Fig. 16.3c ) and is graded in nature (Fig. 16.3i ). Surprisingly, the ampli-
tude of the NKB depolarization is strikingly similar in ARC-KNDy neurons from
gonad-intact vs. GDX adult male mice (Fig. 16.3d ), despite the signifi cantly lower