Beyond the GnRH Axis: Kisspeptin Regulation of the Oxytocin System in Pregnancy and Lactation - Kisspeptin Signaling in Reproductive Biology - page 201

Central Effects of Oxytocin
In addition to release into the circulation, oxytocin is also released into the brain
from centrally projecting neurons, as well as from the dendrites of magnocellular
oxytocin neurons [ 41 ]. While centrally projecting oxytocin neurons have important
functions, the oxytocin release into the brain from magnocellular neuron dendrites
appears most important for regulating peripheral secretion, particularly secretion
underpinned by bursts of action potentials [ 42 ]; blocking the effects of dendritically
released oxytocin by administration of an OTR antagonist SON delays birth [ 14 ].
Therefore, oxytocin release from dendrites might contribute to pulsatile oxytocin
secretion needed for parturition and lactation by facilitating the occurrence and syn-
chronisation of action potential bursts in oxytocin neurons [ 43 ].
Afferent Inputs to Oxytocin Neurons
Like all other neurons, oxytocin neurons receive afferent inputs from many different
peripheral and central sources. The relay of sensory information from the uterus and
nipples is, of course, particularly important in allowing for the Ferguson refl ex (dur-
ing parturition) and milk-ejection refl ex (during lactation). The vagus nerve pro-
vides a major route of sensory input from the periphery to the brainstem and in
particular the nucleus of the solitary tract (NTS) [ 44 ]. In turn, the NTS and the
ventrolateral medulla (VLM) within the medulla oblongata of the brainstem provide
afferent input to the SON and PVN [ 45 ]. Therefore, vagal afferent fi bres provide a
pathway by which factors in the periphery can relay information to the SON to
modulate the secretion of oxytocin. Electrical stimulation of vagal afferents
increases the fi ring rate of some magnocellular neurons [ 46 ] and disrupting the
vagal pathway reduces oxytocin secretion in response to peripheral modulators
[ 47 ]. Brainstem projections are mainly noradrenergic from the A1 group of the
VLM and the A2 group of noradrenergic neurons in the NTS to the SON [ 48 ], and
excitation of A2 noradrenergic neurons excites oxytocin neurons in the SON [ 49 ].
Over half the projections from the brainstem neurons to the SON are activated dur-
ing parturition [ 50 ], and many of these are noradrenergic. During parturition, the
excited A2 neurons release noradrenaline in the SON [ 51 ], contributing to the exci-
tation of oxytocin neurons. This is unlikely to be the only link in the Ferguson refl ex
afferent pathway, but to date the A2 neurons are the only identifi ed population with
a demonstrated role in directly exciting oxytocin neurons during parturition.
Peptides secreted in the periphery also excite oxytocin neurons indirectly, via
vagal afferents to the NTS and subsequent excitatory noradrenergic input to the
SON. Cholecystokinin (CCK) is a peptide hormone that is released from the stom-
ach following food intake and, in addition to inhibiting feeding [ 47 ], CCK increases
the fi ring rate of oxytocin neurons [ 52 ], resulting in the secretion of oxytocin into
the circulation [ 47 ]. The effects of CCK on food intake and oxytocin secretion are