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The Journal of Neuroscience, March 1, 1998, 18(5):1879-1885
Vasopressin Regularizes the Phasic Firing Pattern of Rat
Hypothalamic Magnocellular Vasopressin Neurons
Laurent
Gouzènes,
Michel G.
Desarménien,
Nicolas
Hussy,
Philippe
Richard, and
Françoise C.
Moos
Centre National de la Recherche Scientifique-Unité Propre de
Recherche 9055, Biologie des Neurones Endocrines, Centre de
Pharmacologie Endocrinologie, 34094 Montpellier cedex 05, France
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ABSTRACT |
Vasopressin (AVP) magnocellular neurons of hypothalamic nuclei
express specific phasic firing (successive periods of activity and
silence), which conditions the mode of neurohypophyseal vasopression release. In situations favoring plasmatic secretion of AVP, the hormone
is also released at the somatodendritic level, at which it is believed
to modulate the activity of AVP neurons. We investigated the nature of
this autocontrol by testing the effects of juxtamembrane applications
of AVP on the extracellular activity of presumed AVP neurons in
paraventricular and supraoptic nuclei of anesthetized rats. AVP had
three effects depending on the initial firing pattern: (1) excitation
of faintly active neurons (periods of activity of <10 sec), which
acquired or reinforced their phasic pattern; (2) inhibition of
quasi-continuously active neurons (periods of silences of <10 sec),
which became clearly phasic; and (3) no effect on neurons already
showing an intermediate phasic pattern (active and silent periods of
10-30 sec). Consequently, AVP application resulted in a narrower range
of activity patterns of the population of AVP neurons, with a Gaussian
distribution centered around a mode of 57% of time in activity,
indicating a homogenization of the firing pattern. The resulting phasic
pattern had characteristics close to those established previously for
optimal release of AVP from neurohypophyseal endings. These results
suggest a new role for AVP as an optimizing factor that would foster
the population of AVP neurons to discharge with a phasic pattern known
to be most efficient for hormone release.
Key words:
vasopressin; autocontrol; phasic activity; optimization; supraoptic and paraventricular nuclei; extracellular electrical
activity; hypothalamic magnocellular neurons
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INTRODUCTION |
Most vasopressin (AVP) neurons in
rat supraoptic nucleus (SON) and paraventricular nucleus (PVN) express
a phasic activity characterized by a succession of periods of activity
and silence. This specific pattern depends on intrinsic mechanisms as
well as extrinsic factors such as plasma osmolarity, blood volume, and
pressure (for review, see Poulain and Wakerley, 1982 ; Armstrong, 1995).
During hyperosmotic stimulus or hemorrhage, AVP neurons either acquire
or reinforce a phasic pattern (Brimble and Dyball, 1977; Poulain et
al., 1977; Wakerley et al., 1978), which consequently increases
systemic AVP release (for review, see Dyball, 1988). Hypo-osmotic
stimulation has opposite effects, silencing AVP neurons in
vitro (Oliet and Bourque, 1993a,b) and in vivo (Hussy
et al., 1997). A supplementary control could be exerted by the peptide itself, similar to that described for oxytocin (OT) neurons, the stereotyped bursting activity of which depends on locally released OT
during suckling (Moos and Richard, 1989; Lambert et al., 1993). Indeed,
somatodendritic release of AVP has been demonstrated in both SON and
PVN by morphological and pharmacological studies (Di Scala-Guenot et
al., 1987; Pow and Morris, 1989; Ludwig et al., 1995). This local AVP
release increases during osmotic stimulation and hemorrhage (Neumann et
al., 1993; Ota et al., 1994), two physiological situations that favor
the expression of phasic pattern in AVP neurons. Moreover, local
application of AVP has been shown to modulate the activity of AVP
neurons, although this effect is controversial. AVP has been reported
to decrease (Leng and Mason, 1982; Abe et al., 1983), increase (Inenaga
and Yamashita, 1986), or have no effect on the spontaneous firing
(Carette and Poulain, 1989).
As an attempt to clarify the role of intranuclear AVP release on the
firing rate and firing pattern of AVP neurons, in vivo extracellular recordings of these neurons were performed during juxtamembrane application of various concentrations of AVP, in male or
lactating rats. We report that AVP favors the expression of phasic
activity by presumed AVP neurons and homogenizes the characteristics of
this pattern. A preliminary report of these results has appeared
(Dayanithi et al., 1995).
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MATERIALS AND METHODS |
Experiments were performed on male or female lactating
Wistar rats (Depré; 250-350 gm body weight). In the evening
before the experiments, dams (8-12 d postpartum) were separated from all of their pups except one (~14 hr of separation). Rats were anesthetized with urethane (ethyl carbamate, 1.2 gm/kg; Sigma) applied
by a single intraperitoneal injection. A cannula was inserted into the
jugular vein for intravenous injection of Brietal (9 mg/kg; Lilly) to
supplement anesthesia when necessary. In lactating rats, a thoracic
mammary gland was cannulated and connected to an electromagnetic
pressure transducer (Vigo-Spectramed, Oxnard, CA) to measure
intramammary pressure peaks as an index of OT release. Suckling with 10 pups was applied 3 hr after anesthesia to trigger the milk ejection
reflex (Lincoln et al., 1973). The rats were placed in a stereotaxic
frame. Xylocaine (lydocaine hydrochloride, 1% solution;
Rhône-Poulenc, Rohrer, France) was injected subcutaneously to all
surgical sites and at the points of contact with the stereotaxic frame.
After trepanning, a bipolar stimulating electrode was inserted into the
pituitary stalk at the limit of the neurohypophysis (Anteriority, (A),
4.7; Laterality, (L), 0; Height, (H), 0.5; stereotaxic atlas of
Albe-Fessard et al., 1966) for antidromic identification of magnocellular neurons (SON or PVN neurons). The exact position of the
electrode was attested (1) in lactating rats by a peak of intramammary
pressure evoked by repetitive electrical stimulation of the pituitary
stalk (40 Hz, 0.3-0.5 mA, 0.5 msec for 4 sec), and (2) in male rats by
a posteriori observation of the site of lesion provoked by electrolytic
current (10 mA during a few seconds). Recording glass micropipettes
filled with 0.5 M sodium acetate solution (8-20 M
impedance) were placed in the SON (A, 7-8; L, 1-2.3; H, 2.5-2) or
PVN (A, 6.5-7; L, 0.1-0.7; H, 4-3.5) and connected to conventional
electrophysiological apparatus. Extracellular electrical activities
were displayed on a chart recorder (Astromed SNC, Trappes, France) and
simultaneously stored on computer by means of a Cambridge Electronic
Design (Cambridge, UK) 1401 interface card. Juxtamembrane injections of
AVP close to the recorded neuron were performed using a glass
micropipette glued 20-40 µm above the recording micropipette and
connected to a pneumatic picopump (WPI Inc., Sarasota, FL). Nitrogen
pressure was adjusted to 0.7-1.4 bars according to the tip diameter of
the pressure micropipette (10-20 µm), and drugs were delivered by
applying pressure pulses of 10-30 msec with a square waveform repeated
every 1-10 sec over periods of 2-15 min. Calibration of ejection
pulses performed under microscopic observation revealed that the total
volume ejected for each application varied between 20 and 100 nl.
Because the pipette tip could be partly occluded by the tissue while it
was lowered through the brain, the volume applied was possibly less than estimated. The outflow from the pressure pipette was checked under
binocular observation before and after each recording.
AVP (Boehringer Mannheim, Meylan, France) was used at three
concentrations (0.1, 1, and 10 µM) in artificial CSF
(aCSF, in mM: NaCl, 126.5; NaHCO3, 27.5;
KCl, 2.4; KH2PO4, 0.5;
CaCl2, 1.1; MgCl2, 0.83; and
Na2SO4, 0.5 with glucose, 5.9 g/l). The
pH was adjusted to 7.4, and osmolarity was 300 ± 2 mOsm/l.
Because of variability of the injection parameters used in each
experiment, the drug concentration seen by each neuron tested can
differ.
Identification of neurons and data analysis. The
magnocellular neurons were identified by their antidromic response to
electrical stimulation of the neurohypophysis (the response had a
constant latency, followed high frequency stimulation, and collided
with an orthodromic spike). Presumed AVP neurons, in male or lactating rats, were in most cases characterized by their phasic activity comprising distinct periods of activity separated by periods of silence
(Fig. 1A,B), were also
considered putative AVP neurons, those that fired quasi-continuously
(long periods of activity separated by silences of <10 sec; Fig.
1C, also see Fig. 3A), or that were quasi-silent
(periods of activity of <10 sec; Fig. 2A) but that responded
to AVP by the appearance of a phasic activity. Because (1) phasic
activity is a major characteristic of AVP neurons (for review, see
Armstrong, 1995), (2) only AVP neurons have been shown to possess AVP
receptors (Berlove and Piekut, 1990; Dayanithi et al., 1995), (3) all
OT neurons identified by milk ejection-related activity were found
insensitive to AVP, and (4) none of the 21 AVP-sensitive phasic neurons
recorded from lactating rats during suckling showed milk ejection
bursts, we will refer to the phasic neurons recorded in this study as
AVP neurons. OT neurons displayed a random continuous basal activity,
over which, in lactating rats during the milk ejection reflex, a
characteristic periodic bursting activity developed. The latter
consisted of an intense and brief activation 12-18 sec before each
milk ejection (attested by a peak of intramammary pressure or by a
stretch reaction of the pups). On some occasions, OT (1 ng, i.e., 1 µl of 1 µM solution in 0.9% NaCl; Sandoz, Basel,
Switzerland) was injected into the third ventricle (A, 8; L, 0; H, 3)
to induce or facilitate bursting activity (Freund-Mercier and Richard,
1984). In other cases, a hyperosmotic stimulation was applied (2 ml of
1.5 M NaCl solution, i.p.) to induce specific tonic
activation of OT neurons (Wakerley et al., 1978).
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Figure 1.
Control application of aCSF did not affect firing
of vasopressin neurons. A-C, aCSF application on AVP
neurons displaying different phasic patterns did not change their
characteristics of discharge. D, The activity quotient
during aCSF application (QaCSF in percent)
was plotted against initial values
(Qi). In no case did aCSF application
affect the firing pattern.
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Figure 2.
Excitatory effect of AVP on the firing pattern of
some AVP neurons. A, AVP triggered phasic firing in
quasi-silent neurons. On clearly phasic neurons displaying short
periods of activity, AVP induced an increase in burst duration and a
decrease in the duration of silences (B, C). This effect
was accompanied with a slight decrease (B), an
increase (A), or no effect in the intraburst frequency (C).
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Analysis of the electrophysiological recordings was performed using
both in-house programs and Spike2 analysis software (Cambridge Electronic Design). The firing pattern of AVP neurons was analyzed for
15-20 min before (control period) and during the entire application of
AVP. This pattern was characterized by the following parameters: (1)
f, the mean firing rate during periods of activity called "intraburst frequency" (in spikes/sec); (2) da, the
duration of active periods (in sec); (3) ds, the duration of
silent periods (in sec); and (4) Q, the proportion of time
spent by a phasic cell during burst (calculated by exclusion of silent
periods of >2 sec). This latter parameter is equivalent to the
activity quotient described by Wakerley et al. (1975). For OT neurons
recorded during suckling, the parameters considered were (1) the
background activity (in spikes/sec) and (2) the burst amplitude (total
number of spikes per burst). AVP was considered to affect the firing
pattern of AVP or OT neurons when changes in parameters exceeded 10%
of control values. Indeed, during 5-10 min applications of aCSF, the
changes that occurred in the firing characteristics of eight AVP (Fig. 1A-C) and five OT neurons (data not shown; see Moos
et al., 1997) were always <10%. This is illustrated for AVP neurons
in Figure 1D, in which the Q value
measured during aCSF microinjection (and expressed as a percentage of
the initial Q, Qi) is plotted
as a function of Qi. For OT bursting neurons,
the mean firing rate and burst amplitude were similar during control
period and aCSF application (3.0 ± 0.6 and 3.0 ± 0.6 spikes/sec; 69 ± 12 and 69 ± 12 spikes, respectively). All
values are expressed as mean ± SEM. Statistical significance was
assessed by different tests indicated in Results. Curve fitting was
performed with Origin software (Microcal Software).
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RESULTS |
Effect of AVP on AVP neurons
Recordings were obtained from 39 AVP neurons in either the SON
(n = 26) or PVN (n = 13) from 14 rats.
Three concentrations of AVP were applied, 0.1, 1, and 10 µM on, respectively, 9, 8, and 22 AVP neurons that
displayed different patterns of discharge (phasic, quasi-continuously
active, or quasi-silent neurons). Three different effects of AVP on the
firing pattern were observed: excitatory (Fig. 2), inhibitory (Fig.
3), or no effect (Fig.
4), and these were observed on both PVN
and SON neurons. Changes induced by AVP were sustained and reversible
with a return to control parameter values within 5-10 min after the
end of the application, independently of the dose of AVP or the
duration of the application. Because no difference could be detected
related to the concentration of AVP applied (see below), all results
were pooled.
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Figure 3.
Inhibitory effect of AVP on the firing pattern of
some AVP neurons. AVP depressed firing of a quasi-continuously active
neuron (decrease in intraburst frequency), which progressively acquired a phasic pattern (A). AVP inhibited the phasic
pattern by decreasing the duration of active periods
(B) or increasing the duration of silences
(C). In C, this effect outlasted
the duration of application, was more pronounced during the second
test, and was accompanied by an increase in intraburst frequency.
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Figure 4.
AVP did not affect the firing pattern of some
clearly phasic AVP neurons. AVP applied on clearly phasic neurons did
not affect their firing pattern (A, B). Note that in
B, AVP slightly increased the intraburst frequency, an
effect more pronounced during the second application.
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An excitatory effect was observed for 17 neurons. Nine were
quasi-silent before AVP application and acquired a phasic pattern of
activity (Fig. 2A) with a mean da of
34 ± 8 sec and a mean ds of 19 ± 5 sec. For
eight initially phasic neurons, there was an increase in da
(from 15 ± 4 to 20 ± 3 sec) and a decrease in ds
(from 58 ± 7 to 28 ± 6 sec) (Fig. 2B,C).
Both excitatory effects were characterized by an increase in the
activity quotient Q (from 0.11 ± 0.02 to 0.58 ± 0.04; n = 17). Conversely, AVP had an inhibitory effect
on the activity of 15 neurons. Eight were initially quasi-continuously active neurons and acquired a phasic pattern during the application (Fig. 3A), with da = 23 ± 7 sec and
ds = 9 ± 2 sec. For seven initially clearly
phasic neurons, inhibition consisted in a decrease in da
(from 44 ± 8 to 32 ± 5 sec) and an increase in
ds (from 19 ± 4 to 30 ± 6 sec) (Fig.
3B,C). These inhibitory effects resulted in a decreased
Q (from 0.81 ± 0.03 to 0.61 ± 0.04;
n = 15). AVP had no effect on seven neurons, all
showing clear phasic activity (Fig. 4). AVP affected neither
da nor ds (da, 19 ± 2 vs 20 ± 4 sec; ds, 23 ± 4 vs 21 ± 4 sec), and
consequently, Q was equivalent before and during AVP
application (0.47 ± 0.05 vs 0.49 ± 0.05). Strikingly, it
appeared from these observations that the nature of the AVP effects was
related to the characteristics of the initial pattern of activity of
the neurons. Indeed, AVP seemed to excite mostly neurons with low
initial activity, to inhibit mostly neurons with a high initial
activity, and not to affect those displaying an intermediate phasic
activity.
To characterize this dependence on the initial pattern of activity, we
expressed the values of da, ds, and Q
measured in the presence of AVP (daAVP,
dsAVP, and
QAVP) as a function of their initial
value (dai,
dsi, and
Qi; Fig.
5). Changes in da,
ds, and Q were clearly inversely related to
dai, dsi,
and Qi (Fig. 5). For da and
Q, an apparent linear regression could be fitted when the
data were plotted on a double logarithmic scale, which indicated that
the values of dai and Qi
for which AVP had no effect were 18 sec (Fig. 5A) and 0.56 (Fig. 5C), respectively. The relationship between
dsAVP and dsi was
evident, but the distribution prevented a satisfying fit of the data.
However, it clearly appeared that dsi values
>30 sec tended to be decreased, whereas those <10 sec tended to be
increased. We then compared the mean Qi of
neurons excited by AVP (Qi = 0.11 ± 0.02;
n = 17) and of those inhibited (Qi = 0.81 ± 0.03; n = 15). Student's t tests revealed a significant difference at
p < 0.001, indicating that these neurons belonged to
different populations. Furthermore, both Qi
values differed significantly from 0.50 (p < 0.001), a value corresponding to the mean Qi of
neurons that were unaffected (0.49 ± 0.05; n = 7). We also compared the effect of AVP on neurons now categorized in
three equivalents groups according to their Qi
(Qi  0.33; 0.33 < Qi 0.66; Qi > 0.66;
Fig. 6A). Low
Qi (0.11 ± 0.02, n = 17)
were significantly increased by AVP to a mean value of 0.54 ± 0.04 (p < 0.001, Student's paired t
test). High Qi (0.82 ± 0.03; n = 15) was decreased to 0.63 ± 0.04 (p < 0.01), and intermediate Qi (0.50 ± 0.04, n = 7)
was unaffected (0.54 ± 0.06). Last, we looked at the effect of
AVP on the distribution of Q values. Whereas there was no
significant difference between the averaged values of
Qi (0.45 ± 0.05) and
QAVP (0.57 ± 0.03; n = 39;
p > 0.05), the variance of QAVP
was reduced by greater than four times (from 0.112 to 0.026). Indeed,
as shown in Figure 6B, although the values of
Qi were spread out over the entire range, AVP
induced the distribution of Q to become normal, being fitted
with a Gaussian curve with a mode of 0.57 ± 0.02 and an SD of
0.12.
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Figure 5.
Relationships between the effects of AVP and the
initial firing pattern. The duration of active periods, the duration of
silent periods, and the activity quotient measured during the
application of AVP (daAVP,
dsAVP, and
QAVP, respectively) are expressed as a percentage of their respective initial values
(dai,
dsi, and Qi) and plotted as a function of
dai,
dsi, and
Qi on semilogarithmic scales. In
A and C, lines are
apparent linear regressions fitted with 38/39 data points initially
plotted on a log/log scale. These fits indicate significant
relationships between daAVP and
dai and QAVP and
Qi. Fits cross the 100% line at 18 sec
(da) and 0.56 (Q).
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Figure 6.
Changes in the activity quotient induced by AVP.
A, Effects of AVP on neurons classified in three
categories according to their Qi (limits,
0.33 and 0.66). AVP brought the neurons to fire with an intermediate
Q of ~0.50-0.60. B, Distribution of
AVP neurons (n = 39) according to their activity
quotient before (Qi) and during AVP
(QAVP) application. AVP narrowed the
distribution of Q, which became normal and was well
fitted with a Gaussian curve around a mode value of 0.57.
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AVP had different effects on the intraburst frequency, f,
which was enhanced (Figs. 2A, 4B),
decreased (Fig. 3A), or unaffected (Figs. 2C,
3B, 4A) at all concentrations tested. The
excitatory effect was observed in 46% of the neurons recorded (from
4.7 ± 1.0 to 6.6 ± 1.0 spikes/sec). AVP had no effect in
44% of the neurons (6.8 ± 1.0 vs 6.7 ± 1.0 spikes/sec) and
decreased f (from 10.4 ± 1.1 to 7.7 ± 1.6 spikes/sec) in the remaining neurons (10%). The effects of AVP on
f were not related to the initial firing characteristics or
to the changes in the pattern induced by AVP (Figs. 2-4).
Effect of AVP on OT neurons
Application of AVP (0.1, 1, and 10 µM; 100-300 sec)
did not change the firing rate of OT neurons (3.8 ± 1.2, 3.9 ± 0.9, and 3.6 ± 0.8 spikes/sec before, during, and after
application of AVP, respectively; n = 7). Furthermore,
the bursting pattern (either spontaneous or facilitated by OT;
n = 4; Fig.
7A) and the tonic activation
induced by systemic injection of hyperosmotic saline (n = 3; Fig. 7B) were not affected by AVP.
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Figure 7.
Lack of effect of AVP on OT neurons.
A, AVP did not affect the basal activity or the bursting
pattern of an OT neuron recorded during the milk ejection reflex,
whether the reflex was facilitated by an intracerebroventricular
injection of 1 ng of OT. The number beside each burst
indicates the total number of spikes in that burst. B,
AVP applied on a putative OT neuron did not modify the tonic activation
induced by a systemic hyperosmotic stimulus (2 ml of 9% NaCl,
i.p.).
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DISCUSSION |
In the present work, vasopressin was applied onto magnocellular
presumed AVP neurons to clarify its role in the control of their
electrical activity. The responses observed were attributable to AVP
and not to nonspecific mechanical perturbations, as attested by the
lack of effect of aCSF application. This suggests that our local
pressure microinjections allow the drug to diffuse gently around the
neurons without creating deformation of brain tissue. Furthermore, the
ineffectiveness of AVP to affect OT neurons, which like AVP neurons
possess mechanoreceptors (Oliet and Bourque, 1993a,b), attests to the
specificity of the effects of AVP on AVP neurons.
AVP had different effects on the activity pattern of AVP neurons:
excitatory, inhibitory, or no effect. Qualitatively similar responses
were obtained with the three doses of AVP tested, and no correlation
could be found between the magnitude of the effect and the AVP
concentration. The absence of dose dependency may result from an
already high level of activation of AVP receptors by the lowest
concentration used (0.1 µM; see Dayanithi et al., 1996).
On the other hand, these effects remarkably depended on the initial
activity pattern. Indeed, AVP excited neurons displaying a low activity
quotient, triggering or enhancing phasic activity, and inhibited highly
active neurons; phasic neurons initially displaying intermediate
Q were not affected. Consequently, by reducing the
proportion of neurons displaying very low and very high activity, AVP
narrowed the distribution of Q, which became normal, at a
mode of ~0.57. Therefore, application of AVP resulted in the
homogenization of the firing pattern of the whole population of AVP
neurons. This mean intermediate phasic pattern was characterized by a
duration of active periods (da) of ~20 sec and duration of silences (ds) of 10-30 sec. With regard to the intraburst
frequency, f, AVP also had different effects, but they were
unrelated to the initial pattern of activity. So, AVP regulated the
phasic pattern and firing rate differently and independently.
Inhibitory and excitatory role of AVP
As far back as 1981, Leng had already speculated that AVP could
modulate the phasic pattern of AVP neurons in rats. Thereafter, using
extracellular recordings from rat hypothalamic slices, AVP has been
shown to modify the firing pattern of SON or PVN neurons, but different
reports are contradictory; according to Inenaga and Yamashita (1986),
AVP had an excitatory effect on the firing rate of unidentified PVN
neurons, whereas Leng and Mason (1982) reported that AVP inhibited the
phasic pattern of AVP neurons in SON from Brattleboro rats. By
intracellular recordings on guinea pig hypothalamic slices, Carette and
Poulain (1989) observed that application of AVP did not affect AVP
phasic neurons but depolarized neighboring interneurons projecting onto
AVP neurons. Finally, Abe et al. (1983) reported that AVP depolarized
the membrane but decreased the spontaneous firing rate in most neurons
tested (~69%), the others being either excited (~5%) or
unaffected (~26%). However, when AVP was applied to a previously
hyperpolarized neuron, the inhibitory effect on firing was reversed to
excitatory in both spontaneously active and silent neurons. In
agreement with this observation, dissociated SON neurons, which display
no or little spontaneous activity (M.G. Desarménién,
personal observation), respond to AVP by an influx of calcium through
voltage-dependent calcium channels, attesting for an excitatory effect
of AVP (Dayanithi et al., 1996; Sabatier et al., 1997). The resulting
increase in intracellular calcium concentration could modulate the
phasic pattern of AVP neurons (Bourque, 1986; Andrew, 1987; Inenaga et al., 1992; Li and Hatton, 1995, 1997). This suggests that the inhibitory and excitatory effect of AVP could depend on the initial level of membrane polarization, which itself is known to influence the
firing pattern (Andrew and Dudek, 1984). Such a hypothesis is
corroborated by the present work showing that AVP exerted inhibitory, excitatory, or no effect on AVP neurons according to their initial pattern of discharge.
AVP favors a phasic activity optimizing the neurohypophyseal
AVP release
Previous in vitro experiments using freshly isolated
rat neurohypophyses impaled onto a stimulating electrode have
established a relationship between the activity pattern, the firing
rate, and the release of AVP. Dutton and Dyball (1979) have
demonstrated that stimulating the neurosecretory tissue with a phasic
pattern optimizes AVP release from nerve endings. Thereafter, it was
shown that most of the release of AVP from the neurohypophysis occurs during the first 20 sec of activity (Bicknell et al., 1984; Shaw et
al., 1984), and interruption of firing of >20 sec dramatically enhances systemic release of AVP (Cazalis et al., 1985). These values
are close to the values of da and ds found in
this study. With regard to f, the values measured during AVP
application remain in the range of frequency known to be most efficient
for the release of AVP from neurohypophysis in vitro, i.e.,
frequency of  6 pulses/sec (Dutton and Dyball, 1979). Consequently,
the changes in f induced by AVP are likely to have less
influence on the systemic release of AVP than those in the activity
pattern, as suggested already by Poulain et al. (1988). Therefore, AVP
released intranuclearly in cases of high hormonal need may be
considered as optimizer of the phasic activity pattern of AVP neurons,
which is a major determinant of the amount of AVP released from the
neurohypophysis. Interestingly, although different in nature, the role
of intranuclear OT is also to facilitate a neuronal behavior optimum
for hormonal function, i.e., the suckling-induced synchronous bursting
activity (Moos and Richard, 1989; Lambert et al., 1993). This control
is specific to OT, because AVP is ineffective (Freund-Mercier and Richard, 1984; present data). Thus, the two populations of
magnocellular neurons display specific rhythmic patterns of discharge,
which are controlled and fostered by their respective peptide.
Physiological meaning
Using a dual immunocytochemical labeling procedure, it has been
shown that AVP receptor sites are associated with AVP-containing neurons in SON and PVN (Berlove and Piekut, 1990). Through these autoreceptors, the activity of AVP neurons could be modulated by AVP
released somatodendritically (Neumann et al., 1993) or by the
connections between AVP neurons within the SON (Leng and Wiersma,
1981). These effects could be complemented by a presynaptic action of
AVP on afferent terminals, as recently suggested by Kombian et al.
(1997), or a recurrent action via neighboring interneurons projecting
onto magnocellular neurons (Leng and Dyball, 1983). This modulatory
role would be particularly prominent in physiological situations in
which local AVP release is increased, e.g., during hyperosmotic
stimulation (Neumann et al., 1993) and hemorrhage (Ota et al., 1994).
The intranuclear release of AVP in response to these stimuli has been
shown to be maintained for several hours (Ludwig et al., 1994). One
would then expect sustained modulatory effects of AVP on the firing of
AVP neurons. This should allow the expression of a phasic pattern of
discharge that would be optimal for a sustained systemic AVP release,
in accordance to the physiological demand. Interestingly, a former
study has reported that 6-18 hr dehydration induced 80-100% of AVP
neurons to fire phasically with mean burst duration between 20 and 24 sec and mean silence duration between 13 and 17 sec (Wakerley et al., 1978).
In conclusion, the present work shows that local AVP favors the
expression by AVP neurons of a specific phasic activity known to
optimize the systemic release of AVP. This reveals a new concept of
modulation of neuronal activity by centrally released peptides: the
optimization of a neuronal discharge in accordance with the physiological demand.
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FOOTNOTES |
Received Oct. 1, 1997; revised Dec. 4, 1997; accepted Dec. 10, 1997.
We express our gratitude to David Brown for careful revision of this
manuscript and judicious suggestions for the statistical analyses
performed in this study. Our grateful thanks to Anne Duvoid and Pierre
Fontanaud for their excellent technical assistance.
Correspondence should be addressed to Dr. Françoise C. Moos,
Centre National de la Recherche Scientifique-Unité Propre de Recherche 9055 Biologie des Neurones Endocrines, Centre de
Pharmacologie Endocrinologie-141, rue de la Cardonille, 34094 Montpellier cedex 05, France.
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REFERENCES |
-
Abe H,
Inoue M,
Matsuo T,
Ogata N
(1983)
The effects of vasopressin on electrical activity in the guinea pig supraoptic nucleus in vitro.
J Physiol (Lond)
337:665-685[Abstract/Free Full Text].
-
Albe-Fessard D,
Libouban S,
Stutinsky F
(1966)
In: Atlas stéréotaxique du diencéphale du rat blanc. Paris: Centre National de la Recherche Scientifique.
-
Andrew RD
(1987)
Endogenous bursting by rat supraoptic neuroendocrine cells is calcium dependent.
J Physiol (Lond)
384:451-465[Abstract/Free Full Text].
-
Andrew RD,
Dudek FE
(1984)
Analysis of intracellularly recorded phasic bursting by mammalian neuroendocrine cells.
J Neurophysiol
51:552-566[Abstract/Free Full Text].
-
Armstrong WE
(1995)
Morphological and electrophysiological classification of hypothalamic supraoptic neurons.
Prog Neurobiol
47:291-339[Web of Science][Medline].
-
Berlove DJ,
Piekut DT
(1990)
Co-localization of putative vasopressin receptors and vasopressinergic neurons in rat hypothalamus.
Histochemistry
94:653-657[Web of Science][Medline].
-
Bicknell RJ,
Brown D,
Chapman C,
Hancock PD,
Leng G
(1984)
Reversible fatigue of stimulus-secretion coupling in the rat neurohypophysis.
J Physiol (Lond)
348:601-613[Abstract/Free Full Text].
-
Bourque CW
(1986)
Calcium-dependent spike after-current induces burst firing in magnocellular neurosecretory cells.
Neurosci Lett
70:204-209[Web of Science][Medline].
-
Brimble MJ,
Dyball REJ
(1977)
Characterization of the responses of oxytocin- and vasopressin-secreting neurones in the supraoptic nucleus to osmotic stimulation.
J Physiol (Lond)
271:253-271[Abstract/Free Full Text].
-
Carette B,
Poulain P
(1989)
Vasopressin-sensitive neurons in the lateral paraventricular nucleus area in a guinea pig slice preparation.
Brain Res Bull
22:969-974[Web of Science][Medline].
-
Cazalis M,
Dayanithi G,
Nordmann JJ
(1985)
The role of patterned burst and interburst interval on the excitation-coupling mechanism in the isolated rat neural lobe.
J Physiol (Lond)
369:45-60[Abstract/Free Full Text].
-
Dayanithi G,
Moos F,
Richard PH
(1995)
Vasopressin controls magnocellular vasopressin neurones via V1-type receptors in the rat.
J Physiol (Lond)
489:184-185.
-
Dayanithi G,
Widmer H,
Richard PH
(1996)
Vasopressin-induced intracellular Ca2+ increase in isolated rat supraoptic cells.
J Physiol (Lond)
490:713-727[Abstract/Free Full Text].
-
Di Scala-Guenot D,
Strosser MT,
Richard PH
(1987)
Electrical stimulations of perifused magnocellular nuclei in vitro elicit Ca2+-dependent, tetrodotoxin-insensitive release of oxytocin and vasopressin.
Neurosci Lett
76:209-214[Web of Science][Medline].
-
Dutton A,
Dyball REJ
(1979)
Phasic firing enhances vasopressin release from the rat neurohypophysis.
J Physiol (Lond)
290:433-440[Abstract/Free Full Text].
-
Dyball REJ
(1988)
The importance of bursting in determining secretory response: how does a phasic firing pattern influence peptide release from neurohypophysial vasopressin terminals.
In: Pulsatility in neuroendocrine systems (Leng G,
ed), pp 181-196. Boca Raton, FL: CRC.
-
Freund-Mercier M-J,
Richard PH
(1984)
Electrophysiological evidence for the facilitatory control of oxytocin neurones by oxytocin during suckling in the rat.
J Physiol (Lond)
352:447-466[Abstract/Free Full Text].
-
Hussy N,
Deleuze C,
Pantaloni A,
Desarménien MG,
Moos F
(1997)
Agonist action of taurine on glycine receptors in rat supraoptic magnocellular neurones: possible role in osmoregulation.
J Physiol (Lond)
502:609-621[Abstract/Free Full Text].
-
Inenaga K,
Yamashita H
(1986)
Excitation of neurones in the rat paraventricular nucleus in vitro by vasopressin and oxytocin.
J Physiol (Lond)
370:165-180[Abstract/Free Full Text].
-
Inenaga K,
Akamatsu N,
Nagamoto T,
Ueta Y,
Yamashita H
(1992)
Intracellular EGTA alters phasic firing of neurons in the rat supraoptic nucleus in vitro.
Neurosci Lett
147:189-192[Web of Science][Medline].
-
Kombian SB,
Mouginot D,
Pittman QJ
(1997)
Dendritically released peptides act as retrograde modulators of afferent excitation in the supraoptic nucleus in vitro.
Neuron
19:903-912[Web of Science][Medline].
-
Lambert RC,
Moos FC,
Richard PH
(1993)
Action of endogenous oxytocin within the paraventricular or supraoptic nuclei: a powerful link in the regulation of the bursting pattern of oxytocin neurons during the milk-ejection reflex in rats.
Neuroscience
57:1027-1038[Web of Science][Medline].
-
Leng G
(1981)
The effects of neural stalk stimulation upon firing patterns in the rat supraoptic neurones.
Exp Brain Res
41:135-145[Web of Science][Medline].
-
Leng G,
Wiersma J
(1981)
Effects of neural stalk stimulation on phasic discharge of supraoptic neurones in Brattleboro rats devoid of vasopressin.
J Endocrinol
90:211-220[Abstract/Free Full Text].
-
Leng G,
Mason WT
(1982)
Influence of vasopressin upon firing patterns of supraoptic neurons: a comparison of normal and Brattleboro rats.
Ann NY Acad Sci
394:153-158[Web of Science][Medline].
-
Leng G,
Dyball REJ
(1983)
Intercommunication in the rat supraoptic nucleus.
Q J Exp Physiol
68:493-504[Abstract].
-
Li Z,
Hatton GI
(1995)
Calcium release from internal stores: involvement in generation of burst firing patterns in hypothalamic supraoptic neurons.
J Gen Physiol
106:21-22.
-
Li Z,
Hatton GI
(1997)
Ca2+ release from internal stores: role in generating depolarizing after-potentials in rat supraoptic neurones.
J Physiol (Lond)
498:339-350[Abstract/Free Full Text].
-
Lincoln DW,
Hill A,
Wakerley JB
(1973)
The milk-ejection reflex of the rat: an intermittent function not abolished by surgical levels of anaesthesia.
J Endocrinol
57:459-476[Abstract/Free Full Text].
-
Ludwig M,
Callahan MF,
Neumann I,
Landgraf R,
Morris M
(1994)
Systemic osmotic stimulation increases vasopressin and oxytocin release within the supraoptic nucleus.
J Neuroendocrinol
6:369-373[Web of Science][Medline].
-
Ludwig M,
Callahan MF,
Morris M
(1995)
Effects of tetrodotoxin on osmotically stimulated central and peripheral vasopressin and oxytocin release.
Neuroendocrinology
62:619-627[Web of Science][Medline].
-
Moos F,
Richard PH
(1989)
Paraventricular and supraoptic bursting oxytocin cells in rat are locally regulated by oxytocin and functionally related.
J Physiol (Lond)
408:1-18[Abstract/Free Full Text].
-
Moos FC,
Rossi K,
Richard PH
(1997)
Activation of N-methyl-D-aspartate receptors regulates basal electrical activity of oxytocin and vasopressin neurons in lactating rats.
Neuroscience
77:993-1002[Web of Science][Medline].
-
Neumann I,
Ludwig M,
Engelmann M,
Pittman QJ,
Landgraf R
(1993)
Simultaneous microdialysis in blood and brain: oxytocin and vasopressin release in response to central and peripheral osmotic stimulation and suckling in the rat.
Neuroendocrinology
58:637-645[Web of Science][Medline].
-
Oliet SHR,
Bourque CW
(1993a)
Steady-state osmotic modulation of cationic conductance in neurons of rat supraoptic nucleus.
Am J Physiol
265:1475-1479.
-
Oliet SHR,
Bourque CW
(1993b)
Mechanosensitive channels transduce osmosensitivity in supraoptic neurons.
Nature
364:341-343[Medline].
-
Ota M,
Crofton JT,
Share L
(1994)
Hemorrhage-induced vasopressin release in the paraventricular nucleus measured by in vivo microdialysis.
Brain Res
659:49-54.
-
Poulain DA,
Wakerley JB
(1982)
Electrophysiology of hypothalamic magnocellular neurones secreting oxytocin and vasopressin.
Neuroscience
7:773-808[Web of Science][Medline].
-
Poulain DA,
Wakerley JB,
Dyball REJ
(1977)
Electrophysiological differentiation of oxytocin- and vasopressin-secreting neurones.
Proc R Soc Lond B Biol Sci
196:367-384[Medline].
-
Poulain DA,
Brown D,
Wakerley JB
(1988)
Statistical analysis of patterns of electrical activity in vasopressin and oxytocin-secreting neurones.
In: Pulsatility in neuroendocrine systems (Leng G,
ed), pp 119-154. Boca Raton, FL: CRC.
-
Pow DV,
Morris JF
(1989)
Dendrites of hypothalamic magnocellular neurons release neurohypophysial peptides by exocytosis.
Neuroscience
32:435-439[Web of Science][Medline].
-
Sabatier N,
Richard PH,
Dayanithi G
(1997)
L-, N- and T- but neither P- nor Q-type Ca2+ channels control vasopressin-induced Ca2+ influx in magnocellular vasopressin neurones isolated from the rat supraoptic nucleus.
J Physiol (Lond)
503:253-268[Abstract/Free Full Text].
-
Shaw FD,
Bicknell RJ,
Dyball REJ
(1984)
Facilitation of vasopressin release from the neurohypophysis by application of electrical stimuli in bursts: relevant stimulation parameters.
Neuroendocrinology
39:371-376[Web of Science][Medline].
-
Wakerley JB,
Poulain DA,
Dyball REJ,
Cross BA
(1975)
Activity of phasic neurosecretory cells during haemorrhage.
Nature
258:82-84[Medline].
-
Wakerley JB,
Poulain DA,
Brown D
(1978)
Comparison of firing patterns in oxytocin- and vasopressin-releasing neurones during progressive dehydration.
Brain Res
148:425-440[Web of Science][Medline].
Copyright © 1998 Society for Neuroscience 0270-6474/98/1851879-07$05.00/0
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|
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|
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[Full Text]
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|
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|
|
|
|
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
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|
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Top
Abstract
Introduction
