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results, in part, from increased calcium entry into the axon terminals through
voltage-gated channels to enhance exocytosis. Frequency-facilitation of oxytocin
release is most marked between ~5 and 25 Hz, but continues to increase (albeit at a
slower rate) beyond ~50 Hz. By contrast, as a consequence of frequency-facilitation,
oxytocin neurons fi ring at less than ~4 Hz release little or no oxytocin to the poste-
rior pituitary gland in vivo [
25
]. Hormone secretion is not sustained upon continu-
ous stimulation and there is 'fatigue' in facilitation over time (although this is more
pronounced in vasopressin release), which is rapidly reversed when stimulation is
stopped for a few tens of seconds [
26
]. This frequency-facilitation of oxytocin
release is of particular importance during parturition and lactation.
Under normal physiological conditions, oxytocin neuron fi ring rate is highly
variable between neurons, and the neurons fi re action potentials in a slow continu-
ous or irregular pattern. Generally, the mean fi ring rate of oxytocin neurons is
approximately 3-5 Hz, with intervals of at least 30 ms between consecutive action
potentials [
27
,
28
]. However, during parturition and suckling, co-ordinated intermit-
tent high-frequency bursts are superimposed upon this slow/irregular fi ring
(Fig.
10.1
) [
29
,
30
]. Each burst lasts just 1 or 2 s but the action potential activity is
intense, often with 100 action potentials per burst in each neuron [
31
-
33
]. During
one of these milk-ejection bursts, the intervals between consecutive action poten-
tials are between 6 and 10 ms [
34
]. After a burst, each oxytocin neuron typically
falls silent for a few tens of seconds (allowing the recovery from frequency-
facilitation fatigue).
Remarkably, these milk-ejection bursts are co-ordinated across the population of
oxytocin neurons [
30
]. Because of the co-ordination of bursts between oxytocin
neurons and frequency-facilitation of secretion in each oxytocin neuron, oxytocin is
released into the circulation in high concentrations for short periods. This pattern of
secretion underpins the episodic contraction of the milk ducts for milk ejection, and
similar pattern of activity causes rhythmic contraction of the uterus during parturi-
tion [
35
,
36
]. Because these bursts occur every few minutes and last for only a
couple of seconds, the net increase in fi ring rate only averages about one to two
action potentials per minute for each oxytocin neuron.
Bursting activity occurs in oxytocin neurons only during parturition and lacta-
tion. Other stimuli that excite oxytocin neurons simply increase the continuous fi r-
ing rate of the neurons, which rarely exceeds about 15 action potentials per second
[
27
,
28
]. Additionally, during lactation, oxytocin neurons will only fi re in bursts in
response to suckling and continue to respond to other stimuli in a similar way to
virgin rats [
37
]; indeed stimuli that increase the background fi ring rate can actually
inhibit burst fi ring [
38
]. Therefore, the emergence of bursting behaviour at the end
of pregnancy does not result simply from changes in the structure or intrinsic prop-
erties of oxytocin neurons that fundamentally alter the way in which they respond
to excitatory inputs. Rather, it is the nature of the stimulus that determines whether
bursts will be triggered, and our recent work suggests the possibility that the emer-
gence of a central kisspeptin projection to oxytocin neurons over the course of preg-
nancy might fulfi l this role. Uniquely, milk-ejection bursts, and bursts during
parturition, are synchronised throughout all the magnocellular oxytocin neurons,
with neurons in both the SON and PVN fi ring at the same time [
39
,
40
].
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