Biology Reference
In-Depth Information
Anatomical Connections of Kisspeptin Cells
Efferent Projections
To date, the projections of specifi c subsets of kisspeptin cells have been investigated
using two approaches. The fi rst takes advantage of the co-expression of other neu-
ropeptides and transmitters that are co-expressed uniquely in one population: the
most common example of this is the co-localization of KNDy peptides which can be
used to defi ne the projections arising from ARC kisspeptin cells [
44
,
86
,
105
-
107
].
The second approach has been to combine stereotaxic injections of anterograde
tract tracers (Fluoro-Gold, biotinylated dextran amine) with ICC for kisspeptin, so
that fi bers dual-labeled for both the tracer and kisspeptin can be inferred to have
arisen in the injected region (e.g., ARC) [
108
,
109
].
Dual-label immunostaining of kisspeptin fi bers with either NKB and/or dynorphin
has been the most common approach to selectively analyze the projections of the
ARC kisspeptin population, and has been employed in sheep [
60
], rats [
105
], mice
[
106
], and human tissue [
44
]. In addition, dual-label ICC for NKB and dynorphin,
which is unique to the KNDy population, has been used in rats [
105
], goats [
36
], and
monkeys [
40
]. The results suggest some common, shared projections of ARC
kisspeptin cells across species, but some signifi cant differences as well (Table
3.2
). In
all species examined, fi bers arising from KNDy cells form the densest projections
locally, within the ARC and to the internal zone of the median eminence. There are
also consistent projections of KNDy fi bers to the preoptic region, including the RP3V
in rodents, although the density of these fi bers is generally less than in the ARC. In the
rat, sheep, and goat, a few KNDy fi bers also extend into the external zone of the
median eminence. In sheep, rats, and mice, KNDy cell efferents appear to be more
widespread than in the monkey or human, and include projections in the DMH, BNST,
and in rodents, the PVN, LHA, and septal region (Table
3.2
). Tracer injections into the
ARC of mice combined with kisspeptin ICC revealed a similar distribution of KNDy
efferents as did co-localization of the peptides, with projections to the PVN, DMH,
and LHA, as well as revealing more distant targets including the posterior hypotha-
lamic region and the periaqueductal gray of the midbrain [
6
]. In both rats and mice,
KNDy cells also project across the midline to the contralateral ARC, perhaps serving
to coordinate activity between the KNDy population on both sides of the brain, and
their ipsilateral projections to the POA (and presumably GnRH neurons).
In contrast to the ARC population, much less is known about the projections of
preoptic and RP3V kisspeptin cells. Dual-labeling of kisspeptin and TH in mice has
revealed projections from RP3V kisspeptin cells to the POA, where they contact GnRH
neurons [
64
]. Similarly, anterograde tracer injections into the mouse RP3V, combined
with kisspeptin ICC, revealed a set of projections from this population that includes
several nuclei of the POA, as well as other areas in the hypothalamus and septal region
[
108
]. The latter projection sites closely overlap those of the ARC population, and
include the BNST, PVN, DMH, and periaqueductal gray, as well as projections to the
ipsilateral ARC itself. However, there are a few areas that receive inputs from either the
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