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The Journal of Neuroscience, 2000, 20:RC106:1-5
RAPID COMMUNICATION
Essential Role of D1 But Not D2 Receptors in the NMDA
Receptor-Dependent Long-Term Potentiation at Hippocampal-Prefrontal
Cortex Synapses In Vivo
Hirac
Gurden1,
Masatoshi
Takita2, and
Thérèse M.
Jay1
1 Neurobiologie de l'Apprentissage, de la
Mémoire et de la Communication, Centre National de la Recherche
Scientifique, Unité Mixte de Recherche 8620, 91405 Orsay, France,
and 2 Neuroinformatics Laboratory, National Institute of
Bioscience and Human Technology, Tsukuba, Ibaraki, 305-8566, Japan
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ABSTRACT |
An intact mesocortical dopaminergic (DA) input to the prefrontal
cortex (PFC) has been reported to be necessary for long-term potentiation (LTP) to occur at hippocampal-prefrontal cortex synapses. Here, we investigated the role of D1 and D2 receptors in this NMDA
receptor-dependent LTP. Local infusion of the D1 agonist SKF81297 at an
optimal dose induced a sustained enhancement of hippocampal-PFC LTP,
whereas the D1 antagonist SCH23390 caused a dose-related impairment of
its induction. The D1 agonist effect was mimicked by infusion of a low
dose of the adenylyl cyclase activator forskolin, whereas LTP was
severely attenuated with a protein kinase A inhibitor, Rp-cAMPS.
To further assess the complex interplay between DA and NMDA receptors,
changes in extracellular DA levels in the PFC were estimated during
LTP, and a significant increase was observed immediately after tetanus.
Taken together, these data suggest that D1 but not D2 receptors are
crucial for the DA control of the NMDA receptor-mediated synaptic
response on a specific excitatory input to the PFC. The interactions of these receptors may play a crucial role in the storage and
transfer of hippocampal information in the PFC.
Key words:
prefrontal cortex; dopamine; synaptic plasticity; hippocampus; SCH23390; SKF81297; sulpiride; Rp-cAMPS; forskolin
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INTRODUCTION |
A
critical stage of dopamine (DA) and D1 receptor stimulation appears to
be necessary for a proper performance in prefrontal cortex-related
cognitive tasks like working memory and attentional functions (Williams
and Goldman-Rakic, 1995 ; Granon et al., 2000). In the rat, D1 receptors
(mRNA expression) are mostly localized in deep layers V-VI of the
prefrontal cortex (PFC), whereas D2 receptors are distributed in
superficial and deep layers with lower expression (Gaspar et al.,
1995). Neurons located in deep layers and possessing D1 and D2
receptors are output neurons, thus suggesting how DA could affect
cortical and subcortical transmission (Gaspar et al., 1995; Lu et al.,
1997).
A number of electrophysiological data have pointed out the complex
action (excitatory or inhibitory) of DA in pyramidal PFC neurons but
have also outlined that the action of DA is dependent on the synaptic
strength driven by excitatory inputs on PFC neurons (for review, see
Yang et al., 1999). DA terminals in the PFC are in close proximity to
glutamatergic afferents rising from the hippocampal formation (Carr and
Sesack, 1996). In vivo, synapses of the hippocampal-PFC
fiber pathway can be regulated up and down, expressing potentiation,
depression, or depotentiation of synaptic efficacy, and highly specific
patterns of afferent activation are responsible for these different
forms of plasticity (Jay et al., 1995; Burette et al., 1997; Takita et
al., 1999). Furthermore, these glutamatergic afferents to the PFC are
undoubtedly implicated at least in short-term memory processes
(Floresco et al., 1997; Jung et al., 1998).
We recently reported that an intact mesocortical DA input to the PFC is
necessary for hippocampal-PFC long-term potentiation (LTP) to occur
(Gurden et al., 1999). Whereas stimulation of the ventral tegmental
area (VTA) at a frequency known to evoke DA overflow in the PFC
produces a long-lasting enhancement of the magnitude of
hippocampal-PFC LTP, a depletion of >50% of cortical DA levels
induced a dramatic decrease in this LTP. To obtain further insights
into the complex action of DA in this circuit, we examine whether
potentiation of the hippocampal-PFC pathway increases extracellular DA
levels in the PFC in vivo and whether both D1 and D2-like
receptors could modulate hippocampal-PFC synaptic plasticity.
Additionally, as protein kinase A (PKA) plays a key role in the
induction of hippocampal-PFC LTP (Jay et al., 1998), we explore
further whether the cAMP-PKA pathway plays a role in the
modulatory action of DA on cortical synaptic plasticity. Our findings
provide strong support for an important role of D1 receptors in
modulating hippocampal-PFC plasticity and suggest that DA through D1
receptors could affect the storage of hippocampal information in the
PFC or the transfer of such information to output regions of the PFC.
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MATERIALS AND METHODS |
Electrophysiology. Male Sprague Dawley rats (280-380
gm) were anesthetized with sodium pentobarbital (60 mg/kg, i.p.) and placed in a stereotaxic frame with body temperature maintained at
37°C. The procedures were performed in strict accordance with French Agriculture and Forestry Ministry (decree 874848, license A91429) prerogatives. A concentric bipolar stimulating
electrode was placed in the CA1/subicular region of the ventral
hippocampus (6.3-6.8 posterior to bregma; 5.5 lateral; 4.0-5.8 mm
below pial surface). Recording electrodes (64 µm diameter, two
nickel-chrome wires) fixed to a microdialysis probe (shorter
electrode, same level as the tip of the probe; longer electrode, 200 µm deeper; Fig. 1) were slowly lowered
into the prelimbic area of the PFC (3.0-3.3 mm anterior to bregma;
0.7-1.0 mm lateral; 2.8-3.4 mm below pial surface). The microdialysis
probes (CMA/12; membrane length, 2 mm; diameter, 0.5 mm; cutoff, 20 kDa; CMA, Stockholm, Sweden) were connected via a polyethylene
tubing (FEP) to a microinfusion pump (CMA100) equipped with a liquid
switch (CMA110). Electrophysiological recordings were carried under
perfusion of artificial CSF (ACSF; composition in
mM: 145 NaCl, 2.7 KCl, 1 MgCl2, 1.2 CaCl2, 0.1 ascorbic acid, and 10 glucose, pH 7.4) and drugs. This procedure allowed recordings in intact cortical tissue and a simultaneous control
of infusion of drugs.
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Figure 1.
Schematic diagram representing the location of the
microdialysis probe with external recording electrodes in the prelimbic
area (PL) and the stimulating electrode in the ventral
hippocampus. Black spots represent overlapping
placements of stimulating sites. Sb, Subiculum.
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Stimulation of the CA1/subicular region evokes a characteristic
monosynaptic negativegoing field potential in the PFC with a peak
latency of 18-21 msec. Once a correct signal was detected, we waited
for 2 hr perfusing the probe with ACSF to obtain a stable signal. Test
pulses (80-120 µsec) were delivered every 30 sec at an intensity
that evokes a 70% maximal response (200-400 µA). High-frequency
stimulation consisted of one or two series (6 min apart) of 10 trains
(250 Hz, 200 msec) at 0.1 Hz, delivered at test intensity.
Data were analyzed using A/Dvance software (Mckellar Design).
Postsynaptic potential amplitudes were expressed as a percentage change
of the baseline and analyzed by ANOVA. Correct placement of the
electrodes was confirmed by histology.
Drug delivery. Reverse microdialysis was used to apply DA
drugs and forskolin in the PFC. In control animals, ACSF was
continuously infused at a flow rate of 2 µl/min. In pharmacological
groups, after a stable baseline (40 min), ACSF was replaced for 30 min (20 min before and 10 min after the first tetanus) by ACSF-containing drugs.
Microinjection through a cannula (80 µm diameter) was used to apply
locally the PKA inhibitor Rp-cAMPS. As for microdialysis experiments,
two electrodes fixed to a cannula connected via a polyethylene tubing
to a microinfusion pump (CMA100) allowed both electrophysiological
recordings and drug infusion. Once a stable signal was obtained,
baseline was recorded and ACSF or Rp-cAMPS delivered for 30 min (20 min
before and 10 min after the first tetanus) at a flow rate of 0.013 µl/min.
Drugs. The following drugs were stored as concentrated stock
solutions and, before infusion, dissolved in ACSF (containing ascorbic
acid) to achieve the experimental concentrations: (+)-SKF81297 (0.1-5
mM; Research Biochemicals, Natick, MA),
R-(+)-SCH23390 (2-10 mM; Tocris),
S-( )-sulpiride (5-10 mM, Tocris),
forskolin (25 µM; Tocris), and Rp-cAMPS (300 µM; Sigma). The effective extracellular concentrations of drugs, extrapolated from the relative recovery for DA
drugs through the microdialysis probe, were estimated to be 10-fold
less than the concentrations within the probe.
On-line HPLC analysis of DA level in the PFC. Overall
conditions for recording and microdialysis procedures were the same as
described above. The implanted microdialysis probe (7-9% recovery of
DA in vitro) was continuously perfused with ACSF (2 µl/min), and dialysates were analyzed for DA concentration by
HPLC (EP-300; Eicom, Japan) with an electrochemical detector
(ECD-300). Samples were injected every 10 min directly and
automatically into the HPLC system with a polymeric reverse-phase C18
column (Eicompak CA-50DS; 4.6 × 150 mm) and a graft electrode
(WE-3G) set at 450 mV (vs Ag/AgCl reference electrode). The mobile
phase contained 0.1 M phosphate, 55 mg/l sodium
1-octanesulfonate, 50 mg/l EDTA, and 18% v/v methanol, pH 6.0. A
stable dialysate DA concentration was usually obtained after a minimum
of 2 hr post-implantation of the probe. For data analysis, basal DA
concentration was estimated from an average of three HPLC time points
before tetanization. Electrophysiological hippocampal-PFC response was
obtained during these HPLC periods.
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RESULTS |
Experiment 1: effects of intra-PFC infusions of DA drugs on
hippocampal-PFC LTP
Enhancement of hippocampal-PFC LTP by D1 receptor activation
We first studied the effects of the D1 agonist SKF81297 infused
for 30 min (20 min before tetanus, one series of high-frequency stimulation) in the PFC on hippocampal-PFC LTP (Fig.
2A). During the first
30 min after tetanus (left columns), LTP was significantly larger in the presence of SKF81297 at 0.1 mM
(51.1 ± 3.7% increase compared with baseline, n = 6, p < 0.05) and 1 mM
(70.4 ± 10.1%, n = 8, p < 0.01)
when compared with ACSF controls (37.3 ± 4.1%, n = 7). Ninety minutes later, the enhancement of LTP was still present in
rats infused with 1 mM SKF81297 (right
columns and plotted graph; 59.0 ± 7.7%,
n = 8, p < 0.01) when compared with ACSF controls (22.8 ± 4.9%, n = 7). No effect on
baseline responses was observed for all these doses. LTP in the
presence of a high concentration of SKF81297 (5 mM) showed normal induction and maintenance when
compared with ACSF controls (Fig. 2A, left columns;
37.3 ± 4.1%, n = 8, p > 0.05;
right columns, 28.7 ± 6.1%, n = 8, p > 0.05). However, this concentration of D1 agonist
slightly increased baseline values (8.0 ± 3.70%,
p < 0.05, data not shown) when compared with ACSF
controls (0.4 ± 2.3%). These data demonstrate a clear facilitating effect of D1 agonist on LTP induction; they are consistent with our earlier findings showing a sustained increase in LTP amplitude
when DA was infused before tetanus (Jay et al., 1996).
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Figure 2.
Dose-dependent effects of D1 but not D2 receptor
drugs on hippocampal-PFC LTP. Left graphs, Columns
represent mean ± SEM of the normalized hippocampal-PFC
postsynaptic response amplitude during two stages (left
columns, 0-30 min; right columns, 90-120 min)
after tetanus. The first column on each graph represents
ACSF controls, and the other columns represent the experimental groups.
Right graphs, Changes in normalized hippocampal-PFC
postsynaptic response amplitude are plotted over time for the most
effective dose in each experimental group. Each point represents
mean ± SEM of averaged responses to four test stimuli given at 30 sec intervals. Values are expressed as percentage of change relative to
baseline (40 min). Tetanic stimulation (one or two series) is indicated
by arrowheads. A, D1 agonist SKF81297
increases the amplitude of cortical LTP. Infusion at 0.1 (n = 6) and 1 mM (n = 8) but not at 5 mM (n = 6) evokes a
significant enhancement of cortical potentiation during the first 30 min (left columns) when compared with ACSF controls
(n = 7). Infusion of SKF81297 at 1 mM
induces a persistent facilitation of cortical LTP (right
column and plotted graph). B, D1
antagonist SCH23390 impairs hippocampal-PFC LTP. Infusion at 2 (n = 7), 5 (n = 8), and 10 mM (n = 8) produces a significant
dose-dependent decrease of cortical potentiation in the first 30 min
(left columns) when compared with ACSF controls
(n = 10). A sustained decrease in LTP amplitude is
observed with the highest doses of antagonist (5 and 10 mM;
right column and plotted graph).
C, D2 antagonist sulpiride does not affect
hippocampal-PFC LTP. No significant effect is observed at 5 (n = 6) or 10 mM (n = 8). Representative averaged waveforms (four) on each graph were taken
30 min after induction of LTP: ACSF controls (shaded),
most effective dose in the experimental group (dark).
Calibration: 0.2 mV, 10 msec. Levels of significance, drug versus
control: *p < 0.05, **p < 0.01, ***p < 0.001.
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Impairment of hippocampal-PFC LTP by D1 receptor blockade
To confirm that D1 receptors activation affects hippocampal-PFC
LTP, we tested whether the D1 receptor antagonist SCH23390 had an
effect on the induction of LTP. When SCH23390 was injected in the PFC
in a similar way, we observed a dose-dependent decrease in the
amplitude of hippocampal-PFC LTP (Fig. 2B). In these
experiments, a stronger protocol (two series) was applied in the
hippocampus to induce a stable cortical LTP at least over 2 hr. During
the first 30 min after tetanus (left columns), LTP amplitude
was significantly lower at 2 mM (44.2 ± 4.8%, n = 7, p < 0.05), 5 mM (31.5 ± 5.3%, n = 8, p < 0.001), and 10 mM (9.2 ± 4.7%, n = 8, p < 0.001) when compared with ACSF controls (61.1 ± 5.2%, n = 10). D1 receptor blockade persistently affected LTP during the
subsequent recording time, and LTP was still impaired with 5 mM (26.6 ± 3.6%, n = 8, p < 0.01) and 10 mM (12.6 ± 6.9%, n = 8, p < 0.001;
right columns and plotted graph) 2 hr after
tetanus when compared with ACSF controls (50.0 ± 4.6%,
n = 10). However, no further change was observed with
the lowest dose, 2 mM (Fig. 2B,
right columns; 49.1 ± 7.5, n = 7, p > 0.05). No effect on baseline responses was
observed for any of these doses.
Hippocampal-PFC LTP is not affected by blockade of
D2 receptor
Using a similar protocol as for SCH23390, we then examined whether
the D2 antagonist sulpiride could affect hippocampal-PFC LTP. Figure
2C shows that sulpiride had no effect on either the induction (left columns, 5 mM:
52.6 ± 4.4%, n = 6, p > 0.05;
10 mM: 53.1 ± 10.3%, n = 8, p > 0.05) or the maintenance of LTP (right columns and plotted graph, 5 mM:
41.7 ± 6.4%, n = 6, p > 0.05; 10 mM: 49.5 ± 11.2%, n = 8, p > 0.05) when compared with ACSF controls.
Experiment 2: changes in endogenous DA in the PFC during
hippocampal-PFC LTP
The reduction in hippocampal-PFC LTP by a D1 antagonist suggested
that DA may be released during tetanus and therefore enhanced LTP. As
shown in Figure 3, perfusion of ACSF in
the PFC through microdialysis probes combined with recording of
postsynaptic potential allowed us to measure the dialysate
concentration of cortical DA (every 10 min) before and after tetanic
stimulation of the hippocampus, by using on-line HPLC. Tetanic
stimulation (two series) was applied only when the level of DA in the
PFC was stable for at least 30 min. The mean basal level of DA was
80.2 ± 19.9 fmol/10 min and a significant increase in cortical DA
level compared with baseline was observed immediately after tetanus and
for 20 min after the first tetanus (respectively, 126.7 ± 19.3%,
p < 0.05, and 113.3 ± 9.5, p < 0.05, n = 7).
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Figure 3.
Evoked changes in DA content in the PFC by
hippocampal tetanic stimulation. Top graph, Changes in
the amplitude of cortical postsynaptic potential showing
hippocampal-PFC LTP in rats continuously perfused with ACSF
(n = 7). Each point represents mean ± SEM of
averaged responses to four test stimuli given at 30 sec intervals.
Values are expressed as percentage of change relative to baseline (30 min). Tetanic stimulation is indicated by arrowheads.
Bottom histogram, DA level in the PFC before and after
hippocampal tetanic stimulation. Data are shown as percentages of
control values measured during baseline (mean ± SEM). LTP
increases DA level to 130 and 120% (p < 0.05) of baseline during the first 20 min after tetanus.
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Experiment 3: role of cAMP and PKA in hippocampal-PFC LTP
In view of the preceding results, DA could act through the D1
receptor cascade, involving activation of a G-protein, adenylyl cyclase
(AC), a postsynaptic increase in cAMP levels, and a consequent enhanced
activation of PKA. Indeed, a rapid, NMDA-dependent activation of
cytosolic PKA was found within minutes after induction of LTP in the
hippocampal-PFC pathway in vivo (Jay et al., 1998), thus suggesting an involvement of the cAMP-PKA signal transduction cascade
in the early phases of cortical LTP. To test whether activation of the
AC-cAMP-PKA cascade mimicked the SKF81297 effects, we applied an
activator of AC, forskolin, in the PFC through the microdialysis probe.
As with DA drugs, forskolin was infused during 30 min (20 min before
tetanus, one series of high-frequency stimulation). Figure
4A shows that forskolin
(25 µM) increased significantly early LTP
(left columns, 51.9 ± 5.0%, n = 7, p < 0.05) but not late LTP (right columns,
34.6 ± 5.9%, n = 7, p > 0.05)
when compared with ACSF controls (same as for SKF81297 group). No
effect was observed on baseline.
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Figure 4.
Modulation of hippocampal-PFC LTP amplitude by
drugs directly affecting the AC-cAMP-PKA pathway. The representation
is similar to left graphs in Figure 2. A,
The AC activator forskolin (25 µM, n = 7) enhances the amplitude of LTP during 30 min after tetanus
(p < 0.05, left columns),
whereas no significant effect is observed at a later time (right
columns). B, The PKA inhibitor Rp-cAMPS (300 µM, n = 7) decreases dramatically
cortical LTP amplitude during at least 2 hr after tetanus.
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Knowing the involvement of AC in cortical LTP, we examine whether
blocking PKA by Rp-cAMPS would affect hippocampal-PFC LTP. Rp-cAMPS
(300 µM) injected locally in the PFC before tetanus (30 min duration, 20 min before tetanus; two series of high-frequency stimulation), severely attenuated LTP (12.7 ± 11.7%,
n = 7, p < 0.001) during the first 30 min after tetanus (Fig. 4B, left columns) when
compared with ACSF controls (67.2 ± 10.3%, n = 7). The reduction in amplitude persisted throughout the recording time
and was still significant 2 hr after tetanus (Fig. 4B,
right columns, 25.3 ± 9.6%, n = 7, p < 0.01) when compared with ACSF controls (59.7 ± 5.8%, n = 7). No significant effect on baseline was detected.
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DISCUSSION |
The data presented here demonstrate for the first time the
importance of D1 receptor as a mediator contributing to the occurrence of an NMDA receptor-dependent LTP at hippocampal-PFC synapses in
vivo, suggesting that DA is a crucial executive neurotransmitter in the PFC. First, D1 but not D2 receptor blockade prevented the full
development of cortical LTP; second, stimulation of D1 receptors produced a sustained enhancement of LTP. These findings are consistent with and extend those of previous studies in which local exogenous DA
infusion in the PFC or increase in endogenous cortical DA caused by a
transient stimulation of the VTA produced a long-lasting enhancement in
the magnitude of hippocampal-PFC LTP (Jay et al., 1996; Gurden at al.,
1999).
D1 receptors appear to be crucial for a role of DA in this cortical
LTP. In SKF81297-infused animals, the enhancement of LTP is strong and
persistent at 1 mM. However, when injected at 5 mM, this D1 agonist does not further increase LTP amplitude
compared with controls, suggesting that overstimulation of D1 receptors disrupts the facilitatory effects of DA on synaptic plasticity in the
PFC. These results are in favor of a stepwise control of LTP according
to the amount of D1 receptor stimulation and suggest an optimal D1
receptor activation for proper hippocampal-PFC LTP expression. It is
interesting to note that similar findings have been shown in the monkey
for the modulation of delay-period activity in PFC neurons (Williams
and Goldman-Rakic, 1995). Conversely, for the D1 antagonist, a
concentration-dependent inhibition occurred at the early stages of
cortical LTP, and a threshold concentration (5 mM) to get
long-lasting impairment (at least for 2 hr) was observed. These results
indicate that not only early but also later stages of hippocampal-PFC
LTP are strongly dependent on D1 receptor activation.
The modulatory effects of DA in the hippocampus have been associated
with the late long-lasting, protein synthesis-dependent phase of LTP at
the Schaffer collateral-CA1 synapses (Frey et al., 1990; Huang and
Kandel, 1995), although controversial results have shown that D1
receptors are essential for the early phase (Otmakhova and Lisman,
1996). Interestingly, a recent in vivo study (Swanson-Park
et al., 1999) reported differential effect of DA on two NMDA-dependent
LTPs within the hippocampus: D1 receptors were shown to be involved in
the maintenance of CA1 LTP, whereas these receptors did not modulate
dentate gyrus LTP. If we compare these results to our present data, the
major difference between CA1 and hippocampal-PFC in vivo
LTPs appears to be the short onset of the D1 antagonist effects. The
spatial distribution of DA fibers and D1 receptors as shown in the
monkey (Smiley et al., 1994) but not in the rat should help in
understanding these different DA effects in hippocampal and cortical
LTPs. To our knowledge, only one study on CA1 slices using
[14C]DA has shown that tetanization
produces a significantly enhanced release of DA (Frey et al., 1990). In
the present study, we have also measured a significant increase in DA
release in the PFC during tetanic stimulation of the ventral
hippocampus, which suggests a direct role of DA in the induction of
cortical LTP. One possible explanation could be that tetanized
prefrontal neurons more strongly activate the VTA cells that they
project to, increasing DA release in the PFC. However, the close
proximity of hippocampal and DA terminals in the PFC targeting the same
dendrites in deep layers of the prelimbic area (Carr and Sesack, 1996)
are in favor of a local interplay. Given the fact that the increase in
DA levels in the PFC occurs mainly during tetanization that activates
NMDA receptors (Jay et al., 1995), the putative existence of
heterosynaptic NMDA receptors on DA presynaptic terminals is suggested,
and the following hypothetical model of DA-glutamate interactions is
proposed: during high-frequency stimulation delivered to excitatory
synapses, NMDA receptors are activated both on postsynaptic pyramidal
neurons and mesoprefrontal terminals in the PFC, and as a consequence extracellular DA is increased. Hence, DA acting through postsynaptic D1
receptors modulates powerfully NMDA receptor activation, which triggers
LTP. This hypothesis is supported by previous studies showing (1) an
NMDA-dependent DA release (Feenstra et al., 1995), (2) an enhancement
of NMDA-mediated currents by DA on pyramidal cells (Cepeda et al.,
1992), and (3) an impairment of NMDA-dependent LTP in rats with
decreased DA levels (Gurden et al., 1999), and these NMDA-DA
interactions have also been reported in the striatum (Cepeda and
Levine, 1998; Centonze et al., 1999). In addition, ultrastructural studies looking at synaptic localization of NMDA receptors in the cerebral cortex have already shown the existence of
both homosynaptic receptors on asymmetrical synapses and heterosynaptic receptors on symmetrical synapses (Petralia et al., 1994; DeBiasi et
al., 1996) but until now, a study dealing with the synaptic localization of both DA and glutamatergic receptors in the PFC is lacking.
D1 receptors stimulate AC and provoke an elevation of intracellular
cAMP levels, which in turn activates PKA. Here, we report a transient
facilitation of hippocampal-PFC potentiation by the AC activator
forskolin, indicating that AC is implicated in the early stages of
cortical LTP. These results are comparable with the transient
facilitation of LTP observed with a slight activation of D1 receptors
(SKF81297, 0.1 mM). In addition, blocking the downstream
PKA cascade by Rp-cAMPS injection in the PFC resulted in a dramatic
impairment of cortical LTP, comparable with the strong decrease
observed with the D1 antagonist. This latter observation together with
our previous report showing a rapid NMDA-dependent increase in PKA
activity during induction of hippocampal-PFC LTP (Jay et al., 1998)
strongly suggest that AC-cAMP-PKA pathway plays a key role in the early
stages of cortical LTP. PKA is known to upregulate NMDA receptor
activation by phosphorylation (Blank et al., 1997), therefore through
activation of PKA, D1 receptors stimulation could control the
excitatory synaptic strength in the PFC. Additional studies using a
wider dose range of drugs affecting the AC-cAMP-PKA pathway applied
with DA drugs are needed to assess this hypothesis.
Behavioral and physiological studies suggested that normal cognitive
performance occurs within an optimal range of DA levels and D1 receptor
activation in the PFC (Williams and Goldman-Rakic, 1995; Zahrt et al.,
1997). Here we brought evidence at the synaptic level of a gating
function of D1 receptors on a specific excitatory input to the PFC
arising from the hippocampus. Assuming that LTP is a candidate for
cellular information storage, the present results can be correlated
with the D1 receptor-dependent control of hippocampal information
processing in the PFC previously demonstrated in rats by an impairment
in a spatial delayed task in which ventral hippocampal inactivation was
combined with PFC infusion of SCH23390 (Seamans et al., 1998). The
hippocampal-PFC pathway is also involved in nonspatial events and
novelty detection (Knight and Nakada, 1998; Izaki et al., 2000).
Therefore, to clarify hippocampal information sent to the PFC, it would
be essential to identify at the same time, cortical DA activity
patterns in such behavioral paradigms.
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FOOTNOTES |
Received June 19, 2000; revised Aug. 9, 2000; accepted Aug. 24, 2000.
This study was supported by grants from Centre National de la Recherche
Scientifique, "Fondation pour la Recherche Médicale", "Fondation Cino Del Duca", and Special Coordination Funds for Promoting Science and Technology (Accelerated Basic Research) from
Japan's Science and Technology Agency.
Correspondence should be addressed to Dr. Jay, Neurobiologie de
l'Apprentissage, de la Mémoire et de la Communication, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8620, Université Paris Sud, Bat. 446, 91405 Orsay, France.
E-mail: tm.jay{at}ibaic.u-psud.fr.
This article is published in
The Journal of Neuroscience, Rapid Communications Section,
which publishes brief, peer-reviewed papers online, not in print. Rapid
Communications are posted online approximately one month earlier than
they would appear if printed. They are listed in the Table of Contents
of the next open issue of JNeurosci. Cite this article as:
JNeurosci, 2000, 20:RC106 (1-5). The
publication date is the date of posting online at
www.jneurosci.org.
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REFERENCES |
-
Blank T,
Nijholt I,
Teichert U,
Kügler H,
Behersing H,
Fienberg A,
Greengard P,
Spiess J
(1997)
The phosphoprotein DARPP-32 mediates cAMP-dependent potentiation of striatal N-methyl-D-aspartate responses.
Proc Natl Acad Sci USA
94:14589-14864.
-
Burette F,
Jay T,
Laroche S
(1997)
Reversal of LTP in the hippocampal afferent fiber system to the prefrontal cortex in vivo with low-frequency patterns of stimulation that do not produce LTD.
J Neurophysiol
78:1155-1160.
-
Carr DB,
Sesack SR
(1996)
Hippocampal afferents to the rat prefrontal cortex: synaptic targets and relation to dopamine terminals.
J Comp Neurol
369:1-15.
-
Centonze D,
Gubellini P,
Picconi B,
Calabresi P,
Giacomini P,
Bernardi G
(1999)
Unilateral dopamine denervation blocks corticostriatal LTP.
J Neurophysiol
82:3575-3759.
-
Cepeda C,
Levine M
(1998)
Dopamine and N-methyl-D-aspartate receptor interactions in the neostriatum.
Dev Neurosci
20:1-8.
-
Cepeda C,
Radisavljevic Z,
Peacock W,
Levine MS,
Buchwald NA
(1992)
Differential modulation by dopamine of responses evoked by excitatory amino acids in human cortex.
Synapse
11:330-441.
-
DeBiasi S,
Minelli A,
Melone M,
Conti F
(1996)
Presynaptic NMDA receptors in the neocortex are both auto- and heteroreceptors.
NeuroReport
7:2773-2776.
-
Feenstra M,
van der Weij W,
Botterblom M
(1995)
Concentration-dependent dual action of locally applied N-methyl-D-aspartate on extracellular dopamine in the rat prefrontal cortex in vivo.
Neurosci Lett
201:175-178.
-
Floresco SB,
Seamans JK,
Philips AG
(1997)
Selective roles for hippocampal, prefrontal cortical, and ventral striatal circuits in radial-arm maze tasks with or without a delay.
J Neurosci
17:1880-1890.
-
Frey U,
Schroeder H,
Matthies H
(1990)
Dopaminergic antagonists prevent long-term maintenance of posttetanic LTP in the CA1 region of rat hippocampal slices.
Brain Res
522:69-75.
-
Gaspar P,
Bloch B,
Le Moine C
(1995)
D1 and D2 receptor gene expression in the rat frontal cortex: cellular localization in different classes of efferent neurons.
Eur J Neurosci
7:1050-1063.
-
Granon S,
Passetti F,
Thomas K,
Dalley J,
Everitt B,
Robbins T
(2000)
Enhanced and impaired attentional performance after infusion of D1 dopaminergic receptor agents into the prefrontal cortex.
J Neurosci
20:1208-1215.
-
Gurden H,
Tassin JP,
Jay TM
(1999)
Integrity of the mesocortical DA system is necessary for complete expression of in vivo hippocampal-prefrontal cortex long-term potentiation.
Neuroscience
94:1019-1027.
-
Huang Y,
Kandel E
(1995)
D1/D5 receptor agonists induce a protein-synthesis-dependent late potentiation in the CA1 region of the hippocampus.
Proc Natl Acad Sci USA
92:2446-2450.
-
Izaki Y,
Hori K,
Nomura M
(2000)
Disturbance of rat lever-press learning by hippocampo-prefrontal cortex disconnection.
Brain Res
860:199-202.
-
Jay TM,
Burette F,
Laroche S
(1995)
NMDA receptor-dependent LTP in the hippocampal afferent fibre system to the prefrontal cortex in the rat.
Eur J Neurosci
7:247-250.
-
Jay TM,
Burette F,
Laroche S
(1996)
Plasticity of the hippocampal-prefrontal cortex synapses.
J Physiol (Paris)
90:367-366.
-
Jay TM,
Gurden H,
Yamaguchi T
(1998)
Rapid increase in PKA activity during LTP in the hippocampal afferent fiber system to the prefrontal cortex in vivo.
Eur J Neurosci
10:3302-3306.
-
Jung M,
Qin Y,
McNaughton B,
Barnes C
(1998)
Firing characteristics of deep layer neurons in prefrontal cortex in rats performing spatial working memory tasks.
Cereb Cortex
8:437-450.
-
Knight R,
Nakada T
(1998)
Cortico-limbic circuits and novelty: a review of EEG and blood flow data.
Rev Neurosci
9:57-70.
-
Lu X,
Churchill L,
Kalivas P
(1997)
Expression of D1 receptor mRNA in projections from the forebrain to the ventral tegmental area.
Synapse
25:205-214.
-
Otmakhova NA,
Lisman JE
(1996)
D1/D5 dopamine receptors activation increases the magnitude of early long-term potentiation at CA1 hippocampal synapses.
J Neurosci
16:7478-7486.
-
Petralia R,
Yokotani N,
Wenthold R
(1994)
Light and electron microscope distribution of the NMDA receptor subunit NMDAR1 in the rat nervous system using a selective anti-peptide antibody.
J Neurosci
14:667-696.
-
Seamans JK,
Floresco SB,
Phillips AG
(1998)
D1 receptor modulation of hippocampal-prefrontal cortical circuits integrating spatial memory with executive functions in the rat.
J Neurosci
18:1613-1621.
-
Smiley JF,
Levey AI,
Ciliax BJ,
Goldman-Rakic PS
(1994)
D1 dopamine receptor immunoreactivity in human and monkey cerebral cortex: predominant and extrasynaptic localization in dendritic spines.
Proc Natl Acad Sci USA
91:5720-5724.
-
Swanson-Park J,
Coussens C,
Mason-Parker S,
Raymond C,
Hargreaves E,
Dragunow M,
Cohen A,
Abraham W
(1999)
A double dissociation within the hippocampus of dopamine D1/D5 receptor and beta-adrenergic receptor contributions to the persistence of long-term potentiation.
Neuroscience
92:485-497.
-
Takita M,
Izaki Y,
Jay TM,
Kaneko H,
Suzuki S
(1999)
Induction of stable long-term depression in vivo in the hippocampal-prefrontal cortex pathway.
Eur J Neurosci
11:4145-4148.
-
Williams GV,
Goldman-Rakic PS
(1995)
Modulation of memory fields by dopamine D1 receptors in prefrontal cortex.
Nature
376:572-575.
-
Yang C,
Seamans J,
Gorelova N
(1999)
Developing a neuronal model for the pathophysiology of schizophrenia based on the nature of electrophysiological actions of dopamine in the prefrontal cortex.
Neuropsychopharmacology
21:161-194.
-
Zahrt J,
Taylor JR,
Mathew RG,
Arnsten AFT
(1997)
Supranormal stimulation of D1 dopamine receptors in the rodent prefrontal cortex impairs spatial working memory performance.
J Neurosci
17:8528-8535.
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ABSTRACT
INTRODUCTION
