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NEUROSCIENCE |
1 INSERM U.378, 33077 Bordeaux, France; Université Victor Segalen Bordeaux 2, 33077 Bordeaux France
2 Centre for Research in Neuroscience, Montreal General Hospital and McGill University, Montreal H3G 1A4, Canada
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Abstract |
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(Received 11 March 2006;
accepted after revision 11 April 2006;
first published online 13 April 2006)
Corresponding author S. H. R. Oliet: INSERM U378 – Institut François Magendie, 146, rue Léo Saignat, 33077 Bordeaux Cedex, France. Email: stephane.oliet{at}bordeaux.inserm.fr
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Introduction |
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Previous studies have shown that glutamatergic inputs play an important role in the regulation of SON neuron excitability (Gribkoff & Dudek, 1988, 1990; Parker & Crowley, 1993a,b; Wuarin & Dudek, 1993) and in many instances this role is functionally defined. For example, presynaptic activity in the OVLT-SON pathway is modulated in a manner that increases the frequency of excitatory postsynaptic potentials (EPSPs) and action potential firing rate in SON neurons in proportion with fluid osmolality (Richard & Bourque, 1995). Similarly, the brief (2–4 s) and high frequency (40–80 Hz) bursts of action potentials displayed by OT neurons prior to milk ejection are thought to result from afferent volleys of glutamatergic EPSPs (Jourdain et al. 1998). The actions of glutamate in the SON are mediated through ionotropic AMPA and NMDA receptors (AMPARs and NMDARs), as well as by metabotropic glutamate receptors (Wuarin & Dudek, 1993; Schrader & Tasker, 1997; Stern et al. 1999). In particular, AMPARs and NMDARs are activated during fast excitatory transmission in the SON, and inward current flowing through AMPARs mediates most of the EPSPs observed at the normal resting potential of VP and OT neurons (Wuarin & Dudek, 1993; Stern et al. 1999). NMDARs are also involved in other cellular processes associated with their Ca2+ permeability, including regenerative voltage oscillations (Hu & Bourque, 1992) and somatodendritic hormone release (De Kock et al. 2004). Moreover, blocking NMDARs inhibits phasic activity in VP neurons and attenuates the bursting behaviour of OT cells during the milk ejection reflex (Nissen et al. 1994; Moos et al. 1997).
Studies in other brain regions have shown that NMDARs can play a critical role in the induction of long-term synaptic changes such as long-term potentiation (LTP) and long-term depression (LTD) (for a review see in Malenka & Nicoll, 1999; Malenka & Bear, 2004). These forms of activity-dependent plasticity, respectively, mediate persistent increases and decreases in AMPAR-dependent EPSPs and can therefore alter the relative weight of affected synapses compared to others. In brain areas such as the hippocampus such effects contribute to associative learning and memory (Lynch, 2004). Whether activity-dependent plasticity occurs at excitatory synapses on SON neurons is unknown. In this study therefore we examined if glutamatergic afferents to SON neurons can express different forms of activity-dependent synaptic plasticity, whether NMDAR play a role in such phenomena, and if activity-dependent LTP can be induced in a functionally defined pathway.
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Methods |
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Acute hypothalamic slices were obtained using procedures similar to those previously described (Oliet & Poulain, 1999). Briefly, Wistar female rats (1–2 months old) were anaesthetized with isofluorane (100% O2 and 5% isoflurane for 1 min) and decapitated. The brain was quickly removed and placed in ice-cold artificial cerebrospinal fluid (ACSF) saturated with 95% O2 and 5% CO2. Thin coronal slices (300 µm) were cut with a vibratome (Leica) from a block of tissue containing the hypothalamus. Slices including the SON were hemisected along the midline and allowed to recover for at least 1 h before recording. A slice was then transferred into a recording chamber where it was submerged and continuously perfused (1–2 ml min–1) with ACSF at room temperature. The composition of the ACSF was (mM): 123 NaCl, 2.5 KCl, 1 Na2HPO4, 26.2 NaHCO3, 1.3 MgCl2, 2.5 CaCl2 and 10 glucose (pH 7.4; 295–300 mosmol kg–1).
Hypothalamic explants were prepared as previously described (Ghamari-Langroudi & Bourque, 1998). Briefly, Long-Evans male rats were killed by decapitation and the brain rapidly removed. A block of tissue containing the basal hypothalamus was excised using razor blades and pinned to the slanted Sylgard base of a recording chamber. Explants were superfused (0.5–1 ml min–1) with carbogenated (95% O2 and 5% CO2), warmed (31–32°C) ACSF containing (mM): 121 NaCl, 3 KCl, 26 NaHCO3, 1.3 MgCl2, 2 CaCl2 and 10 glucose (pH 7.4; 295–300 mosmol kg–1).
Patch-clamp and intracellular recordings
Magnocellular neurons in hypothalamic slices were visually identified using infrared differential interference contrast microscopy (Olympus BX50WI microscope). Patch-clamp recording pipettes (3–5 M
) were pulled from borosilicate glass (1.2 mm o.d., 0.6 mm i.d., Clark Electromedical) and filled with an internal solution containing (mM): 120 potassium gluconate, 1.3 MgCl2, 1 EGTA, 10 Hepes and 0.1 CaCl2 (adjusted to pH 7.1 with KOH; 295–300 mosmol kg–1). For experiments involving a pairing protocol, the internal solution contained (mM): 130 CsCl, 10 NaCl, 10 Hepes, 1 EGTA, 5 QX-314 chloride and 0.1 CaCl2 (adjusted to pH 7.1 with CsOH; 295–300 mosmol kg–1). Signals were filtered at 2 kHz and digitized at 5 kHz via a DigiData 1200 or 1300 interface (Axon Instruments, Inc., Union City, CA, USA). Series resistance (6–20 M) was monitored online and cells were excluded from data analysis if more than a 15% change occurred during the course of the experiment. Membrane currents were recorded in voltage clamp mode using either an Axopatch-1D or a Multiclamp 700A amplifier (Axon Instruments) and analysed on-line using pCLAMP 9 (Axon Instruments). Data, reported as means ±
S.E.M., were compared statistically with paired or unpaired Student's t test. Significance was assessed at P < 0.05. Excitatory postsynaptic currents (EPSCs) were evoked at 0.066 Hz through a stimulating glass electrode filled with ACSF and placed in the area dorsal to the SON (Kombian et al. 1996). The amplitude of the EPSCs was measured by calculating the average of a 2–3 ms windows around the peak of the EPSC relative to baseline. The data were normalized to the average value obtained during the 10–15 min period prior to applying the LTP or LTD inducing stimulus.
Intracellular recordings were obtained using sharp micopipettes prepared from 1.2 mm o.d. glass capillary tubes (A-M Systems Inc, Carlsborg, WA, USA) pulled on a P87 Flaming-Brown puller (Sutter Instrument Co., Novato, CA, USA). Pipettes were filled with 2 M potassium acetate, yielding a DC resistance of 70–150 M. Recordings of membrane voltage were obtained though an Axoclamp 2A amplifier (Axon Instruments). Voltage recordings were performed in continuous current clamp mode. Electrical stimulation of the OVLT was performed via a bipolar electrode constructed from a pair of nichrome wires (62 µm o.d.) separated by 
0.3 mm.
Pairing-induced LTP was obtained by pairing membrane depolarization (0 mV) with synaptic stimulation at 2 Hz for 45 s. High frequency stimulation (HFS)-induced LTP was obtained by using a 100 Hz train of stimuli for 1 s in current clamp mode (I = 0), repeated 4 times at 15 s intervals. The LTD-induction protocol was a 5 Hz/3 min train of stimuli given in current clamp mode (I = 0).
The paired-pulse facilitation ratio was calculated as the amplitude ratio of the second EPSC over the first EPSC elicited 50 ms later. The coefficient of variation (CV) of EPSCs was calculated as CV = S.D./mean. Data were compared statistically using the non-parametric Mann-Whitney test or the parametric paired t test accordingly. Significance was assessed at P < 0.05. All data are reported as means ± S.E.M.
Drugs
All drugs were bath-applied. Appropriate stock solutions were made and diluted with ACSF immediately before application. QX-314 chloride (Alomone Labs, Jerusalem, Israel) was diluted directly in the patch-solution. Drugs used were 6,7-dinitroquinoxaline-2,3-dione (DNQX), 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA; Sigma), D(–)-2-amino-5-phosphono-pentanoic acid (D-AP5), ifenprodil hemitartrate and bicuculline methobromide (Tocris).
All experiments were conducted in accordance with the European Animal Care Guidelines and Directives. The tissue harvesting protocol for hypothalamic explants was approved by the McGill University Animal Care Committee.
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Results |
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We first tested whether synaptic NMDARs were activated in response to focal afferent stimulation of glutamatergic inputs in acute hypothalamic slices. In the presence of bicuculline (20 µM) to inhibit GABAA receptors, stimulation of the area dorsal to the SON evoked excitatory postsynaptic currents (EPSCs) that reversed near 0 mV (Fig. 1). At negative potentials, these EPSCs had fast kinetics whereas they were very slow at positive voltage (Fig. 1A). The current–voltage (I–V) relationship measured 5 ms after the stimulation was linear whereas it was inwardly rectifying when the current amplitude was measured 40 ms later (Fig. 1B). Under conditions where AMPARs were inhibited with a specific antagonist, DNQX (10 µM), the I–V curve was no longer linear but presented a rectification typical of the voltage-dependent Mg2+ inhibition of NMDARs (Fig. 1C and D) (Mayer et al. 1984). This was confirmed by the complete inhibition of the response by a specific NMDAR antagonist, D-AP5 (50 µM; Fig. 1E).
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LTP of glutamatergic transmission in the SON
LTP experiments began by acquiring a control baseline of 10 min duration during which glutamatergic afferent inputs were stimulated at low frequency (0.066 Hz) to evoke AMPAR-mediated EPSCs. This frequency did not produce any time-dependent drift in the amplitude of evoked EPSCs. Because NMDAR-dependent forms of LTP are impaired by prolonged intracellular dialysis by the patch pipette solution (Malinow & Tsien, 1990), we induced LTP within 15 min after gaining whole-cell access. We first attempted to potentiate glutamatergic transmission by applying repetitive tetanic stimulations. As show in Fig. 2A, high frequency stimulation (HFS; 4 x 100 Hz – 1 s) of glutamatergic inputs produced a persistent increase of evoked EPSC amplitude. This potentiation lasted as long as the recording remained stable and averaged 194 ± 27% of control responses 30 min after the induction (n = 12; P < 0.05). The kinetics of the EPSCs remained unaffected after the tetanic stimulation. To test for the implication of NMDARs in the induction of this LTP, we repeated the protocol in the presence of 50 µM D-AP5. As illustrated in Fig. 2B, tetanus-induced LTP was completely prevented under conditions where NMDARs were blocked. In this set of experiments, the EPSC amplitude measured 30 min after HFS had a mean of 98 ± 26% of control (n = 11; P > 0.05). It thus appears that NMDARs in the SON are activated during tetanic stimulations of glutamatergic afferent inputs leading to long-term enhancement of excitatory transmission.
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To induce long-term depression (LTD) at glutamatergic synapses in the SON, afferent fibres were stimulated at 5 Hz for 3 min in current clamp mode at resting membrane potential. This protocol caused a pronounced long-lasting reduction of evoked-EPSC amplitude (57 ± 12% of control; n = 11; P < 0.05; Fig. 5A). To determine whether this form of synaptic plasticity depended on NMDAR activation, we repeated these experiments in the presence of D-AP5 in the bathing solution. Under such conditions, the evoked EPSCs were no longer depressed following the induction protocol (98 ± 11% of control; n = 11; P > 0.05), confirming the role of NMDARs in the induction of this LTD (Fig. 5B).
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Recent reports have show that specific blockade of NR2B- and NR2A-containing receptors in the hippocampus inhibited LTD and LTP, respectively (Liu et al. 2004). These findings suggested that NMDA receptor subtypes govern the direction of hippocampal plasticity. Because most of the NMDA receptors present at glutamatergic synapses in SON neurons contain NR2B, we tested whether they were required for the induction of both LTP and LTD. As illustrated in Fig. 7A, pairing-induced LTP was not obtained in the presence of 10 µM ifenprodil (95 ± 12%; n = 5; P > 0.05). Similarly, stimulating afferent fibres at 5 Hz for 3 min did not cause LTD in the presence of the antagonist (106 ± 28%; n = 7; P > 0.05; Fig. 7B). It seems therefore that, unlike what has been reported at hippocampal synapses, NR2B-containing receptors are implicated in the induction of LTP and LTD in the SON.
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To determine if maintained expression of synaptic plasticity in the SON depends on presynaptic or postsynaptic changes, we examined paired-pulse facilitation (PPF) before and after induction of either LTP or LTD. For these experiments, two stimuli of equal intensity were applied within a very short interval (50 ms). In such a protocol, the amount of facilitation of the second response is inversely correlated to transmitter release probability (Zucker & Regehr, 2002). As illustrated in Fig. 8, PPF was not affected following HFS-induced LTP (n = 6), pairing-induced LTP (n = 7) or LTD (n = 7) of glutamatergic transmission. Moreover, the relative magnitudes of LTP and LTD were not significantly correlated (R = 0.07; P > 0.05) with changes in PPF ratio (Fig. 8B). Another index of changes in presynaptic function is the inverse of the squared coefficient of variation (1/CV2). This parameter that reflects trial-to-trial variation was compared before and after the induction of long-term synaptic changes. As illustrated in Fig. 8C, neither LTP, induced by HFS (n = 10) or pairing (n = 6), nor LTD (n = 11) significantly modified 1/CV2 (P > 0.05). Taken together, these findings argue against the involvement of a change in the probability of transmitter release to explain these long-term modifications of synaptic strength and therefore support a postsynaptic locus of expression of LTP and LTD in the SON.
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The data presented above indicate that long-lasting activity-dependent changes in synaptic strength can be induced at unidentified glutamatergic inputs activated by focal stimulation near the SON neurons in coronal hypothalamic slices. To determine if a functionally defined glutamatergic projection can also exhibit activity-dependent long-term plasticity, we performed sharp microelectrode recordings from supraoptic neurons in hypothalamic explants to monitor the excitatory input that originates from neurons in the OVLT (Fig. 9A). EPSPs were evoked at a low frequency (0.066 Hz) in the continuous presence of 10 µM bicuculline. Individual EPSPs were evoked during the steady-state phase of the electrotonic response to a hyperpolarizing current pulse injected through the recording electrode to monitor the input resistance of the postsynaptic cell throughout the protocol (Fig. 9B). Small changes in holding current were applied as necessary to maintain the holding potential to a constant value near resting potential. As illustrated in Fig. 9B, HFS of the OVLT caused an immediate enhancement of synaptic transmission that decayed progressively over 5–7 min. Following this period of post-tetanic potentiation (PTP), the amplitude of the EPSP evoked by OVLT stimulation remained typically twice as large as control for the remainder of the recording (Fig. 9C), despite the absence of significant changes in input resistance (e.g. Fig. 9B). Indeed, in seven cells tested in different preparations, the mean amplitude of the EPSP recorded under control conditions was 4.8 ± 0.4 mV, whereas that observed during the maintained phase that followed PTP was 8.5 ± 1.1 mV (P < 0.05). Although these experiments were performed in a different rat strain than that used for slice experiments, we did not observe any relevant differences. We cannot rule out the possibility, however, that slight differences in LTP properties exist between these two strains of animals.
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Discussion |
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LTP and LTD at glutamatergic synapses
In the present study, we observed that HFS of glutamatergic inputs to SON neurons causes a long-term enhancement of synaptic strength. A similar potentiation is observed when afferent activity is paired with membrane depolarization. Induction of this LTP was dependent upon NMDAR activation since D-AP5 prevented completely the persistent increase in EPSC amplitude. Analysis of paired-pulse facilitation and of 1/CV2, two indicators of presynaptic function, suggests that LTP expression is not associated with an increase of the probability of transmitter release. LTP in SON neurons therefore is similar to that prevailing in pyramidal neurons of the CA1 region of the hippocampus and which is the best-characterized form of long-term synaptic plasticity in the central nervous system (Nicoll, 2003). It has been clearly established that during HFS or pairing induction protocols, activation of NMDARs leads to a large Ca2+ entry in the dendrites, thereby triggering a cascade of intracellular events resulting in AMPAR insertion at the synapses (Malenka & Nicoll, 1999; Nicoll, 2003). Intacellular Ca2+ buffering with BAPTA prevented LTP in our recordings indicating that a similar cellular mechanism is likely to account for the long-term enhancement of evoked EPSCs observed in the SON. Interestingly, AMPAR insertion was recently described in hypothalamic magnocellular neurons (Gordon et al. 2005), suggesting that such mechanism could underlie LTP expression in SON neurons.
A different form of potentiation of glutamatergic transmission has been reported in SON neurons in response to HFS of local inputs (Kombian et al. 2000). This phenomenon, however, is entirely different from the LTP described here since it is short-lasting (5–15 min), NMDAR-independent, it affects miniature but not evoked EPSCs and is expressed presynaptically. We did notice a transient increased in spontaneous EPSCs following HFS but we believe that it reflected post-tetanic potentiation of the stimulated inputs (Zucker & Regehr, 2002). Nevertheless, we cannot rule out the possibility that short-term potentiation of miniature EPSCs (Kombian et al. 2000) occurs in response to our HFS protocol.
LTD, the opposite phenomenon of LTP, was observed at the same glutamatergic synapses showing LTP in the SON. This persistent reduction was obtained in response to stimulation of the afferents at a frequency of 5 Hz for 3 min while the recorded neurons were in current-clamp mode at resting membrane potential. This induction protocol reliably induces a pronounced LTD in the CA1 region of the hippocampus (Oliet et al. 1997). NMDAR activation is required for the induction of LTD in SON neurons, as revealed by the use of D-AP5. PPF and 1/CV2 analyses suggest that LTD expression did not result from a reduction in the probability of transmitter release. It seems therefore that LTD in the SON is similar to the NMDAR-dependent form of LTD observed in the CA1 region of the hippocampus (Oliet et al. 1997). In that region, activation of NMDARs during low frequency stimulation of Schaffer collaterals causes moderate Ca2+ entry in the dendrites, triggering a cascade of intracellular events, distinct from those involved in LTP induction (Malenka & Bear, 2004), and which leads to a removal of AMPARs from the plasma membrane (Luscher et al. 2000).
That a synapse exhibits LTP rather than LTD depends on the extent of Ca2+ entry into the postsynaptic cell upon NMDAR activation. This has been demonstrated in an elegant series of experiments where reducing the number of NMDARs activated during an LTP-induction protocol resulted in long-term depression (Cummings et al. 1996). However, it has been suggested recently that induction of hippocampal LTP and LTD was mediated by the activation of distinct populations of NMDARs (Liu et al. 2004). In this structure, activation of synaptic NMDARs that do not contain the NR2B subunit caused LTP whereas activation of extrasynaptic NMDARs, which contain NR2B, induced LTD. In other terms, it appears that LTP induction protocols such as HFS or pairing are appropriate to stimulate synaptic NMDARs, whereas low frequency stimulation, or other LTD inducing protocols, cause glutamate spillover, thereby activating extrasynaptic NMDARs. Although glutamate spillover and activation of non-synaptic NMDARs could also be involved in the generation of LTD in the SON, this hypothesis cannot be tested based on pharmacological assessment of subunit, unlike in the CA1 region of the hippocampus, since a majority of NMDARs at glutamatergic synapses in the SON appear to contain the ifenprodil-sensitive NR2B subunit. Interestingly, blockade of NR2B receptors caused a defect in LTP and LTD indicating that this NMDAR subtype was required for the induction of both LTP and LTD in the SON.
LTP–LTD relevance in the SON
NMDAR-dependent long-term changes in synaptic strength have been shown to contribute to a variety of neural processes that involve cognition, such as addiction (Wolf, 2003), hyperalgesia (Willis, 2002; Ji et al. 2003), as well as learning and memory (Lynch, 2004). Our results suggest that similar processes may also play an important role in the neuroendocrine hypothalamus. What might be the role of long-term synaptic plasticity in a neural system which is designed to respond to physiological variables that vary on a moment to moment basis? The answer to this question may reside in the fact that LTP and LTD are not irreversible processes, but that they can mediate bi-directional adaptations in synaptic strength over a time scale of minutes. These mechanisms therefore provide an opportunity to adapt the weight of individual excitatory inputs in response to changes in physiological demand. For instance, during parturition and lactation OT neurons display synchronized bursts of action potentials which may be elicited in part by high frequency volleys of presynaptic glutamatergic EPSPs (Jourdain et al. 1998). It is possible therefore that such a pattern of synaptic activation leads to NMDAR-dependent LTP thereby selectively enhancing the weight of these particular synapses relative to others and, as a consequence, sensitizing OT neurons to those particular inputs. Indeed, this phenomenon could explain the progressive increase in burst intensity that is observed during successive episodes of milk-ejection at the onset of individual periods of feeding (Belin & Moos, 1986), and facilitate the activation of OT neurons throughout lactation. Further studies will be required to establish if LTP and LTD play a role in the bursting activity of OT neurons during lactation.
Long-term plasticity in the OVLT-SON pathway
The results obtained with coronal hypothalamic slices indicated that synapses expressing both AMPARs and NMDARs can clearly exhibit activity-dependent plastic changes during focal stimulation proximal to the SON. It is possible, however, that synapses recruited during focal stimulation produce postsynaptic responses that do not reflect physiological conditions (e.g. by stimulating spatially constrained synapses that are not normally coactivated). It was therefore important to establish whether changes in synaptic strength can also occur in an anatomically defined axonal projection. Intracellular recordings from SON neurons in superfused hypothalamic explants revealed that glutamatergic synapses formed by the axons of neurons in the OVLT, most of which are osmosensitive, could be potentiated in response to HFS. Other fibres passing trough or close to the OVLT, might be recruited when this region is stimulated, including fibres originating from the subfornical organ (SFO). Whether this SFO-SON pathway, or other pathways can also undergo potentiation remains to be determined.
Indeed, OVLT neurons activated by hyperosmolality can commonly fire bursts of action potentials displaying instantaneous firing rates of 80 Hz or more (Gentles, 1987), suggesting that LTP of OVLT-SON synapses might occur under these conditions. Previous studies have shown that osmoregulatory mechanisms (i.e. water intake and antidiuresis) cause a gradual and slow (15–30 min) recovery of the plasma osmotic pressure following a hyperosmotic stimulus (Poulain & Wakerley, 1982). Since the overall presynaptic activity OVLT neurons varies in proportion with plasma osmolality (Richard & Bourque, 1995), it seems reasonable to hypothesize that a prolonged period of slow firing on the descending phase of the neuronal response could eventually lead to a depotentiation of OVLT-SON synapses, via LTD, as plasma osmolality returns to baseline. While further studies will be required to test these hypotheses, the reversible induction of LTP at glutamatergic OVLT-SON synapses could provide a significant increase in the determinant role of this pathway on the electrical and secretory activity of SON neurons under hyperosmotic conditions.
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References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Csaki A, Kocsis K, Kiss J & Halasz B (2002). Localization of putative glutamatergic/aspartatergic neurons projecting to the supraoptic nucleus area of the rat hypothalamus. Eur J Neurosci 16, 55–68.[CrossRef][Medline]
Cummings JA, Mulkey RM, Nicoll RA & Malenka RC (1996). Ca2+ signaling requirements for long-term depression in the hippocampus. Neuron 16, 825–833.[CrossRef][Medline]
De Kock
CP, Burnashev
N, Lodder
JC, Mansvelder
HD
&
Brussaard
AB (2004). NMDA receptors induce somatodendritic secretion in hypothalamic neurones of lactating female rats. J Physiol
561, 53–64.
Gentles SJ (1987). Patterned afferent activity and synaptic plasticity in the magnocellular neurosecretory system. MSc Thesis, McGill University, Montreal, Canada.
Ghamari-Langroudi
M
&
Bourque
CW (1998). Caesium blocks depolarizing after-potentials and phasic firing in rat supraoptic neurones. J Physiol
510, 165–175.
Gordon GR, Baimoukhametova DV, Hewitt SA, Rajapaksha WR, Fisher TE & Bains JS (2005). Norepinephrine triggers release of glial ATP to increase postsynaptic efficacy. Nat Neurosci 8, 1078–1086.[CrossRef][Medline]
Gribkoff VK & Dudek FE (1988). The effects of the excitatory amino acid antagonist kynurenic acid on synaptic transmission to supraoptic neuroendocrine cells. Brain Res 442, 152–156.[CrossRef][Medline]
Gribkoff
VK
&
Dudek
FE (1990). Effects of excitatory amino acid antagonists on synaptic responses of supraoptic neurons in slices of rat hypothalamus. J Neurophysiol
63, 60–71.
Hu
B
&
Bourque
CW (1992). NMDA receptor-mediated rhythmic bursting activity in rat supraoptic nucleus neurones in vitro. J Physiol
458, 667–687.
Ji RR, Kohno T, Moore KA & Woolf CJ (2003). Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci 26, 696–705.[CrossRef][Medline]
Jourdain
P, Israel
JM, Dupouy
B, Oliet
SHR, Allard
M, Vitiello
S, Theodosis
DTT
&
Poulain
DA (1998). Evidence for a hypothalamic oxytocin-sensitive pattern generating network governing oxytocin neurons in vitro. J Neurosci
18, 6641–6649.
Kombian
SB, Hirasawa
M, Mouginot
D, Chen
X
&
Pittman
QJ (2000). Short-term potentiation of miniature excitatory synaptic currents causes excitation of supraoptic neurons. J Neurophysiol
83, 2542–2553.
Kombian
SB, Zidichouski
JA
&
Pittman
QJ (1996). GABAB receptors presynaptically modulate excitatory synaptic transmission in the rat supraoptic nucleus in vitro. J Neurophysiol
76, 1166–1179.
Liu
L, Wong
TP, Pozza
MF, Lingenhoehl
K, Wang
Y, Sheng
M, Auberson
YP
&
Wang
YT (2004). Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic plasticity. Science
304, 1021–1024.
Luscher C, Nicoll RA, Malenka RC & Muller D (2000). Synaptic plasticity and dynamic modulation of the postsynaptic membrane. Nat Neurosci 3, 545–550.[CrossRef][Medline]
Lynch
MA (2004). Long-term potentiation and memory. Physiol Rev
84, 87–136.
Malenka RC & Bear MF (2004). LTP and LTD: an embarrassment of riches. Neuron 44, 5–21.[CrossRef][Medline]
Malenka
RC
&
Nicoll
RA (1999). Long-term potentiation: a decade of progress?
Science
285, 1870–1874.
Malinow R & Tsien RW (1990). Presynaptic enhancement shown by whole-cell recordings of long-term potentiation in hippocampal slices. Nature 346, 177–180.[CrossRef][Medline]
Mayer ML, Westbrook GL & Guthrie PB (1984). Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature 309, 261–263.[CrossRef][Medline]
Moos FC, Rossi K & Richard P (1997). Activation of N-methyl-D-aspartate receptors regulates basal electrical activity of oxytocin and vasopressin neurons in lactating rats. Neuroscience 77, 993–1002.[CrossRef][Medline]
Nicoll RA (2003). Expression mechanisms underlying long-term potentiation: a postsynaptic view. Philos Trans R Soc Lond B Biol Sci 358, 721–726.[CrossRef][Medline]
Nissen R, Hu B & Renaud LP (1994). N-methyl-D-aspartate receptor antagonist ketamine selectively attenuates spontaneous phasic activity of supraoptic vasopressin neurons in vivo. Neuroscience 59, 115–120.[CrossRef][Medline]
Oliet SHR, Malenka RC & Nicoll RA (1997). Two distinct forms of long-term depression coexist in CA1 hippocampal pyramidal cells. Neuron 18, 969–982.[CrossRef][Medline]
Oliet
SHR
&
Poulain
DA (1999). Adenosine-induced presynaptic inhibition of IPSCs and EPSCs in rat hypothalamic supraoptic nucleus neurons. J Physiol
520, 815–825.
Parker
SL
&
Crowley
WR (1993a). Stimulation of oxytocin release in the lactating rat by a central interaction of 
1-adrenergic and -amino-3-hydroxy-5-methylisoxazole-4-propionic acid-sensitive excitatory amino acid mechanisms. Endocrinology
133, 2855–2860.[Abstract]
Parker
SL
&
Crowley
WR (1993b). Stimulation of oxytocin release in the lactating rat by central excitatory amino acid mechanisms: evidence for specific involvement of R,S--amino-3-hydroxy-5-methylisoxazole-4-propionic acid-sensitive glutamate receptors. Endocrinology
133, 2847–2854.[Abstract]
Poulain DA & Wakerley JB (1982). Electrophysiology of hypothalamic magnocellular neurons secreting oxytocin and vasopressin. Neuroscience 7, 773–808.[CrossRef][Medline]
Richard D & Bourque CW (1995). Synaptic control of rat supraoptic neurones during osmotic stimulation of the organum vasculosum lamina terminalis in vitro. J Physiol 489, 567–577.[Medline]
Schrader
LA
&
Tasker
JG (1997). Presynaptic modulation by metabotropic glutamate receptors of excitatory and inhibitory synaptic inputs to hypothalamic magnocellular neurons. J Neurophysiol
77, 527–536.
Stern
JE, Galarreta
M, Foehring
RC, Hestrin
S
&
Armstrong
WE (1999). Differences in the properties of ionotropic glutamate synaptic currents in oxytocin and vasopressin neuroendocrine neurons. J Neurosci
19, 3367–3375.
Williams K (1993). Ifenprodil discriminates subtypes of the N-methyl-D-aspartate receptor: selectivity and mechanisms at recombinant heteromeric receptors. Mol Pharmacol 44, 851–859.[Abstract]
Willis WD (2002). Long-term potentiation in spinothalamic neurons. Brain Res Brain Res Rev 40, 202–214.[CrossRef][Medline]
Wolf
ME (2003). LTP may trigger addiction. Mol Interv
3, 248–252.
Wuarin JP & Dudek FE (1993). Patch-clamp analysis of spontaneous synaptic currents in supraoptic neuroendocrine cells of the rat hypothalamus. J Neurosci 13, 2323–2331.[Abstract]
Zucker RS & Regehr WG (2002). Short-term synaptic plasticity. Annu Rev Physiol 64, 355–405.[CrossRef][Medline]
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  K. J. Iremonger and J. S. Bains Integration of Asynchronously Released Quanta Prolongs the Postsynaptic Spike Window J. Neurosci., June 20, 2007; 27(25): 6684 - 6691. [Abstract] [Full Text] [PDF]
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 G. R. J. Gordon and J. S. Bains Can homeostatic circuits learn and remember? J. Physiol., October 15, 2006; 576(2): 341 - 347. [Abstract] [Full Text] [PDF]
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) and 40 ms (
) after stimulation. Note the rectification when the current was measured later on the trace. C and D, evoked EPSCs and corresponding I–V curve obtained in the presence of DNQX. Traces are averages of 5–10 consecutive sweeps. E and F, representative examples of the inhibitory effects of 50 µM D-AP5 and 10 µM ifenprodil on evoked EPSCs recorded in the presence of DNQX. Traces are averages of 5–10 consecutive sweeps.
) and LTD (
). C, summary bar graph of 1/CV2 values measured before (filled bars) and after (open bars) the induction of HFS-LTP, pairing LTP and LTD. Note that 1/CV2 was not affected by any of these long-term changes.