Electrophysiology of Kisspeptin Neurons - Kisspeptin Signaling in Reproductive Biology - page 343

expressing hypothalamic neurons, such as the POMC or the SF-1/VMH neurons;
ER deletion in POMC neurons reduces castration-induced increase in gonadotro-

pin levels at least in the female [ 22 ]. Dopaminergic and GHRH neurons located
within the arcuate nucleus also express ER

α

α [ 23 , 24 ]. NPY/AgRP neurons do not

express ER [ 25 ]. Multiple extrahypothalamic neurons, such as cholinergic, adren-

ergic, serotonergic, and/or the dopaminergic neurons, also express sex steroid
receptors; further studies will be required to determine whether these inputs modu-
late the activity of ARC-KNDy neurons.
Post-castration-induced increases in LH secretion could also, theoretically, be
sustained by mechanisms not requiring KNDy neurons. For example, cholinergic
neurons express sex steroid receptors [ 26 , 27 ], and cholinergic fi bers make close
contact with GnRH neurons [ 28 ]. Moreover, acetylcholine directly activates GnRH
neurons via nicotinic receptors and a nicotinic receptor antagonist, mecamylamine,
signifi cantly reduces castration-induced increases in LH secretion [ 29 ]. Thus, both
KNDy cell-dependent and -independent mechanisms may subserve the castration-
induced increase in gonadotropin secretion.
It should be noted that although the reduced fi ring activity of KNDy neurons in
GDX slices may appear paradoxical, the fi nding that a vast majority of KNDy cells
(90%) share the quiescent state in GDX slices also implies that KNDy neurons in
the GDX state are primed for synchronized activity upon arrival of an excitatory
input. In contrast, only half of the KNDY cells are in the same fi ring state in slices
taken from gonad-intact mice, which may explain the lower amplitude of LH pulses
in intact vs. GDX mice.

α

Morphology of ARC-KNDy Neurons and Modulation
by Sex Steroids

Reduced levels of circulating sex steroids in menopausal women and overectomized
monkeys have long been known to induce hypertrophy in NKB somata in the arcu-
ate nucleus [ 30 , 31 ] (which can now be presumed to be KNDy neurons). We have
observed a similarly remarkable hypertrophy in ARC-KNDy neurons in male mice
following gonadectomy, using neurobiotin-fi lling in conjunction with whole cell
patch-clamp recordings in vitro (Fig. 16.2a, b ). ARC-KNDy neurons, that have
bipolar or tripolar morphologies with long processes, doubled in soma cross-
sectional area following gonadectomy (Fig. 16.2c ). This increased cross-sectional
area, presumably, underlies the drop in membrane resistance and associated changes
in the intrinsic membrane properties of KNDy-GDX neurons described above.
Detailed analyses will be required to determine if these somatic changes are also
accompanied by changes in dendritic processes. Thus, modulation by sex steroids
may be a general property of ARC-KNDy neurons across species, allowing them to
convey sex steroid feedback from the gonads [ 19 , 32 , 33 ].