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1 Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, 77225; and 2 Department of Biochemistry and Biophysical Sciences, University of Houston, Houston, Texas 77204
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ABSTRACT |
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 Abstract
 Introduction
Methods
Results
Discussion
References
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Nakanishi, Keiko, Fan Zhang, Douglas A. Baxter, Arnold Eskin, and John H. Byrne. Role of calcium-calmodulin-dependent protein kinase II in modulation of sensorimotor synapses in Aplysia. J. Neurophysiol. 78: 409-416, 1997. The Ca2+-calmodulin-dependent protein kinase II (CaMKII) inhibitor, {1-[N,O - bis(5 - isoquinolinesulfonyl) - N - methyl - L - tyrosyl] - 4 - phenylpiper azine} (KN-62), was used to investigate the role of CaMKII in synaptic transmission and serotonin (5-HT)-induced facilitation in Aplysia. Application of KN-62 (10 µM) by itself increased the amplitude of excitatory postsynaptic potentials (EPSPs) at sensorimotor synapses in pleural-pedal ganglia. Moreover, in the presence of KN-62, 5-HT-induced short-term facilitation was attenuated. Application of KN-62 by itself slightly increased the duration of action potentials in isolated sensory neuron somata but did not block spike broadening produced by 5-HT. KN-62 had no effect on excitability of isolated sensory neuron somata nor did it block 5-HT-induced enhancement of excitability. These results indicate that the attenuation of short-term facilitation by KN- 62 is not due to modulation of the membrane currents contributing to 5-HT-induced spike broadening or enhancement of excitability. Rather, these data are consistent with the hypothesis that CaMKII contributes to the regulation of sensorimotor connections and that it has a role in spike-duration-independent processes contributing to short-term facilitation.
Plasticity of the connections between sensory neurons and their follower motor neurons in Aplysia has been used extensively as a model system to study the cellular and molecular mechanisms of simple forms of learning such as sensitization (for recent reviews see Byrne and Kandel 1996 Aplysia californica were obtained from Alacrity Marine Biological Specimens (Redondo Beach, CA) and Marine Specimens Unlimited (Pacific Palisades, CA). Animals (70-300 g) were maintained in aquaria containing aerated artificial seawater (ASW; Instant Ocean, Aquarium Systems, Mentor, OH) at ~15°C. Before dissection, animals were weighed and anesthetized by injection of a volume of isotonic MgCl2 equal to one-half of their body volume. Pleural-pedal ganglia were removed and placed in a Sylgard (Dow Corning, Midland, MI)-lined recording chamber (volume 0.5 ml) containing a 50:50 solution of isotonic MgCl2:ASW. The connective tissue overlying the ganglion was removed surgically. The 50:50 solution then was exchanged ~100 times with ASW that was buffered with 10 mM Tris (pH 7.4).
Measurements of spike duration and excitability
Clusters of sensory neuron somata were isolated surgically from pleural ganglia and were pinned to the floor of a recording chamber containing ASW (Sugita et al. 1992 Chemicals
KN-62 was purchased from Sigma and Seikagaku America.KN-04, an inactive form of KN-62, was purchased from Seikagaku America. KN-62, KN-04, and calmidazolium (Sigma) were dissolved in dimethyl sulfoxide (DMSO). The final concentration of DMSO in the bath did not exceed 0.5% (vol/vol), a concentration that has no effects on the membrane currents in sensory neurons (Baxter and Byrne 1990b Data analysis
To examine the effects of KN-62 on the efficacy and 5-HT-induced changes of synaptic connections, excitability, or spike duration, two t-tests were performed. First, a t-test was performed between the pre-5-HT EPSPs in the inhibitor and the control groups. The values for each group were obtained by normalizing the average value of the three trials in the pre-5-HT period to the average value of the three trials in the baseline period (Fig. 1). Second, a t-test was performed between the post-5-HT EPSPs in the inhibitor and the control groups. The values for each group were obtained by normalizing the average of the three trials in the post-5-HT period to the average value of the three trials in the pre-5-HT period (Fig. 1). A P value of <0.05 (two-tailed) was considered significant.
KN-62 increased the amplitude of EPSPs and attenuated 5-HT-induced facilitation
To examine the role of CaMKII in sensorimotor synaptic transmission in Aplysia, single action potentials were elicited repeatedly in sensory neurons before and after the application of 10 µM KN-62. Control experiments were identical except that KN-04 was used instead of KN-62. The role of CaMKII in facilitation was tested by comparing the effects of 5-HT in the presence of KN-62 with the effects of 5-HT in controls (Fig. 1). Figure 2A illustrates a typical result. In the control experiments, repeated stimulation (ISI = 5 min) of the sensory neuron led to synaptic depression. Application of 5-HT led to synaptic facilitation (Fig. 2A1). Figure 2A2 illustrates the effects of KN-62. Application of KN-62 by itself increased the amplitude of EPSP. In addition,KN-62 attenuated the facilitation produced by 5-HT. Average data are presented in Fig. 2A3, and further analyses of the data are illustrated in Fig. 2, B and C. The mean amplitude of the three control EPSPs during the pre-5-HT period was 80.9 ± 3.9% of the baseline (mean ± SE, n = 23; Fig. 2B). In contrast, the mean amplitude of the three KN-62 EPSPs during the pre-5-HT period was 108.8 ± 4.6% of the baseline (n = 12). The KN-62-induced increase in the amplitudes of EPSPs was statistically significant (t33 = 4.39, two tailed P < 0.001). In the post-5-HT period, the mean amplitude of the control EPSPs was 159.9 ± 12.6% of the pre-5-HT period, whereas the mean amplitude of theKN-62 EPSPs was 91.7 ± 7.0% of the pre-5-HT period (Fig. 2C). This difference was statistically significant(t33 = 3.74, two tailed P < 0.007). These results suggested that CaMKII may have a dual role in regulating transmitter release and 5-HT-induced facilitation.
KN-62 did not affect the excitability of sensory neurons nor did it affect 5-HT-induced enhancement of excitability
The effects of KN-62 on synaptic efficacy and on 5-HT-induced facilitation may be due to an action of KN-62 on membrane currents in sensory neurons. To investigate this possibility, we examined the effects of KN-62 on excitability and spike broadening in isolated somata of sensory neurons. KN-62 (10 µM) by itself had no effect on the excitability of sensory neurons (Fig. 3, A1 and A2). Figure 3B illustrates the mean changes in excitability (control, 113.7 ± 4.9% versus KN-62, 127.5 ± 7.6%). These effects were not statistically significant (t17 = 1.55). After application of 5-HT, there was an increase in excitability in both the control and KN-62 groups. Figure 3C illustrates the mean changes in excitability produced by 5-HT (5-HT, 322.3 ± 62.5% versus 5-HT + KN-62, 248.2 ± 21.5%). There was also no statistically significant difference between these two groups (t17 = 1.07). These results indicate that the attenuation of 5-HT-induced synaptic facilitation by KN-62 (Fig. 2C) was probably not due to block of the membrane current(s) that contribute to the regulation of excitability. The 5-HT-induced enhancement of excitability in Aplysia is believed to be due to PKA-mediated closure of S-K+ channels (Baxter and Byrne 1990a
KN-62 slightly increased spike duration of sensory neurons but did not block 5-HT-induced spike broadening
The 5-HT-induced spike broadening is believed to be due to the modulation of both a transient voltage-dependent K+ channel (Ik,v) and the S-K+ current (Baxter and Byrne 1989
An increasing body of evidence indicates that CaMKII is an important kinase involved in synaptic plasticity in both invertebrate and vertebrates (see Byrne et al. 1993 Specificity of KN-62
The evidence for the involvement of CaMKII in synaptic transmission and its plasticity is based on the use ofKN-62, which is considered a specific inhibitor of CaMKII. KN-62 does not affect PKA, PKC, myosin light chain kinase, and Ca2+/CaM-dependent phosphodiesterase in rat, even at a concentration of 100 µM (Ishikawa et al. 1990 Interrelationships among kinases
CaMKII, PKA, and PKC have at least one common action in that they all seem to participate in 5-HT-induced short-term facilitation of the sensorimotor connections (Table 1). Two mechanisms are believed to contribute to the facilitation. One mechanism for facilitation is broadening of the sensory neuron spike, whereas a second one is via spike-duration-independent (SDI) processes (see Byrne and Kandel 1996
Dual actions of CaMKII
The effects of KN-62 were complex and cannot be readily explained by monotonic actions at a single site. Rather, the effects may be explained by assuming that CaMKII has an inhibitory effect on release at low levels of activation (i.e., in the absence of 5-HT or at low levels of 5-HT) and a facilitatory effect on release at higher levels of 5-HT. [A ceiling effect is unlikely, because the difference between the groups after the treatment with 5-HT in the presence and the absence of KN-62 is still significant when the EPSP amplitudes were normalized to the baseline (P < 0.05, Fig. 2A3), instead of to the pre-5-HT group (Fig. 2C)]. In addition, the degree of broadening produced by KN-62 was small compared with that produced by 5-HT (Fig. 4A3). Thus we speculate that higher levels of CaMKII (e.g., in the presence of 5-HT) facilitate transmitter release and these facilitatory effects override the inhibitory effects at low levels of CaMKII (e.g., in the absence of 5-HT). It is unlikely that a site of these facilitatory effects is the action potential, because KN-62 did not attenuate 5-HT-induced spike broadening (Fig. 4C). A second possible site for the facilitatory effects of CaMKII on release is the release mechanism itself.
INTRODUCTION
Abstract
Introduction
Methods
Results
Discussion
References
; Byrne et al. 1993; Kandel et al. 1987). The synaptic plasticity associated with sensitization is induced, at least in part, by serotonin (5-HT), acting via at least two kinases, adenosine 3
,5-cyclic monophosphate (cAMP)-dependent protein kinase [protein kinase A (PKA)] (Bacskai et al. 1993; Bernier et al. 1982; Greenberg et al. 1987; Ocorr and Byrne 1985) and Ca2+/phospholipid-dependent protein kinase [protein kinase C (PKC)] (Braha et al. 1990; Sacktor and Schwartz 1990; Sossin and Schwartz 1992; Sugita et al. 1992).
, 1985). In addition, the level of mRNA for calmodulin (CaM) is increased by treatment with 5-HT (Eskin et al. 1993; Zhang et al. 1995; Zwartjes et al. 1991). The electrophysiological effects of CaMKII have not been examined, however. To investigate the role of CaMKII in the efficacy and modulation of sensorimotor connections, we examined the effects of a specific inhibitor of CaMKII, {1-[N, O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine} (KN-62)(Tokumitsu et al. 1990), on transmission and 5-HT-induced facilitation of sensorimotor synapses in pleural-pedal ganglia. We also examined the effect of KN-62 on the excitability and spike duration in sensory neurons to determine whether the effects of KN-62 on the synaptic efficacy could be attributed to actions on one or more of the membrane currents.
METHODS
Abstract
Introduction
Methods
Results
Discussion
References
35 mV were used in these studies.
). During tests, motor neurons were hyperpolarized by ~30 mV to prevent the EPSP from triggering an action potential. Measurements of input resistance of the motor neuron (while the cell was hyperpolarized) were made before each test by intracellularly injecting 1-s, 1- or 2-nA hyperpolarizing constant current pulses. After three baseline trials, ganglia were exposed to KN-62 (10 or 1 µM) or control vehicle (N-{1-[N-methyl-p-(5isoquinolinesulfonyl ) benzyl ] 2 - ( 4 - phenylpiperazine ) ethyl } - 5 isoquinolinesulfonamide) (KN-04); an inactive form of KN-62, 10 or 1 µM) 15 min before the application of 15 µM 5-HT (Fig. 1). The amplitudes of EPSPs were normalized to the baseline EPSP, which was defined as the average of three EPSPs (0, 5, and 10 min) recorded immediately before the application of KN-62 or the control vehicles.
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FIG. 1.
Experimental protocol. Effects of {1-[N, O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine} (KN-62) were examined by using 9 test stimuli (trials) delivered at an interstimulus interval (ISI) of 5 min. Each test consisted of eliciting a single action potential in a tail sensory neuron with a suprathreshold depolarizing current pulse and recording monosynaptic exitatory postsynaptic potential (EPSP) elicited in follower tail motor neuron. Within 1 min after third stimulus (time = 10 min), experimental or control solution was applied to bath; 15 min after treatment with KN-62 or control, 15 µM serotonin (5-HT) subsequently was applied to bath. Value of each trial was normalized to mean of 3 baseline trials preceding treatment.
, 1994), and the preparation was maintained at 15 ± 1°C. Two-electrode current-clamp techniques (Sugita et al. 1992, 1994) were used. The membrane potential of the sensory neuron was monitored and was adjusted via current injection to a potential of 45 mV ~30 s before each stimulus. Individual action potentials were elicited at an ISI of 5 min. The duration of action potentials elicited by a 3-ms, 5-nA current pulse was measured as the time between the peak of the spike and the point of the repolarizing phase at which the membrane potential was 10% of the peak amplitude of the spike (Sugita et al. 1992). In a separate series of experiments, excitability was measured as the number of action potentials elicited during 1-s,2-nA constant-current pulses (ISI = 5 min). Measurements of spike duration and excitability were performed in different cells to avoid possible interactions between the two stimulus paradigms.
). TFP (Sigma) and 5-HT (creatinine sulfate complex, Sigma) were dissolved in ASW.
RESULTS
Abstract
Introduction
Methods
Results
Discussion
References
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FIG. 2.
KN-62 (10 µM) by itself increased amplitude of EPSPs and attenuated 5-HT-induced synaptic facilitation. A1 and A2: typical results illustrating action potentials elicited in sensory neurons (SN, bottoms) and EPSPs produced in motor neurons (MN, tops) during baseline (t = 0 min), 5 min after treatment (t = 15 min), 15 min after treatment (just before application of 5-HT, t = 25 min), and 5 min after 5-HT application (t = 30 min). A3: summary data from 35 experiments: 23 controls and 12 KN-62. B: summary data illustrate that KN-62 significantly enhanced amplitudes of EPSPs. C: summary data illustrate that KN-62 significantly attenuated 5-HT-induced facilitation. Summary data in this and subsequent figures show means ± SE.
in the control group and 11.3 ± 1.5 M in theKN-62 group (t33 = 0.74).
; Zhang et al. 1995; Zwartjes et al. 1991), we also examined the effects of inhibitors of CaM (25 µM calmidazolium and 50 µM TFP) on the amplitudes of EPSPs. Calmidazolium and TFP had effects on the pre-5-HT EPSPsand 5-HT-induced facilitation similar to, but weaker than, KN-62. Calmidazolium and TFP increased the amplitude of the pre-5-HT EPSP (control, 78.2 ± 9.6%, n = 6 vs.calmidazolium, 86.8 ± 4.1%, n = 7; and control, 85.2 ± 14.7%, n = 5 vs. TFP, 109.5 ± 20.4%, n = 4). These effects were not statistically significant, however. In addition, both inhibitors appeared to attenuate 5-HT-induced facilitation (control 292.5 ± 86.0% vs. calmidazolium 147.0 ± 11.6% and control 216.0 ± 65.0% vs. TFP 98.3 ± 9.4%), but again the effects were not statistically significant.
; Klein et al. 1982; Pollock et al. 1985; Siegelbaum et al. 1982). Thus these results suggest that CaMKII does not affect the S-K+ channel of sensory neurons nor 5-HT-induced modulation of these channels.
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FIG. 3.
KN-62 (10 µM) did not change excitability of sensory neuron nor did it affect 5-HT-induced enhancement of excitability. A1: typical results illustrating excitability of a sensory neuron in control saline (baseline), after application of KN-62 and after application of 5-HT to bath, which still contained KN-62. A2: summary data from 10 control [(N-{1-[N-methyl-p-(5-isoquinolinesulfonyl ) benzyl ] 2 - ( 4 - phenylpiper azine)ethyl}-5-isoquinolinesulfonamide) (KN-04)] and 9 KN-62 experiments. B: summary data for control and KN-62 groups during pre-5-HT period. C: 5-HT-induced enhancement of excitability in presence (KN-62 + 5-HT) and absence (control + 5-HT) of KN-62. There was no significant difference between KN-62 and control groups in Band C.
, 1990a; Hochner and Kandel 1992; Klein et al. 1982; Pollock et al. 1985; Siegelbaum et al. 1982; Sugita et al. 1994). Application of KN-62 (10 µM) led to a small broadening of the action potential but did not affect 5-HT-induced spike broadening (Fig. 4A2). Average data from 10 experiments in control (KN-04) and 10 experiments in KN-62 are illustrated in Fig. 4A3. During the pre-5-HT period, the mean spike duration was102.0 ± 1.7% in the control group and 107.3 ± 1.9% in the KN-62 group (Fig. 4B). The difference was small but statistically significant (t18 = 2.10, two tailed P < 0.05). This difference was in the same direction as the effect of KN-62 on EPSPs (Fig. 2B), so the KN-62-induced increase in synaptic efficacy may be due to its effect on spike duration. In the presence of 5-HT, the mean duration of spikes in the control group was 157.8 ± 16.5% of the pre-5-HT period and the mean duration in the KN-62 group was 172.8 ± 25.1% of the pre-5-HT period(Fig. 4C). The difference was not statistically significant(t18 = 0.50). This result suggests that KN-62 had no effect on the membrane currents contributing to 5-HT-induced spike broadening.
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FIG. 4.
KN-62 (10 µM) slightly increased spike duration but had no effect on 5-HT-induced spike broadening. A1: a control experiment. KN-04 (10 µM) did not affect either spike duration or 5-HT-induced spike broadening. A2: a KN-62 experiment. KN-62 slightly increased duration of action potential, but did not affect 5-HT-induced spike broadening. A3: summary data, from 10 control (KN-04) and 10 KN-62 experiments. B: summary data revealed a significant difference between KN-62 and control groups during pre-5-HT period. C: summary data revealed no significant difference between 5-HT-induced broadening inpresence (KN-62 + 5-HT) and absence (control +5-HT) of KN-62.
DISCUSSION
Abstract
Introduction
Methods
Results
Discussion
References
; Lisman 1994 for reviews; see also Chapman et al. 1995; Malenka et al. 1989; Malinow et al. 1989; Silva et al. 1992; Wang et al. 1994). The present finding that a CaMKII inhibitor, KN-62, attenuated the facilitation produced by 5-HT supports the hypothesis that CaMKII is involved in synaptic plasticity, in general, and in heterosynaptic facilitation of the Aplysia sensorimotor synapse in particular. Thus in addition to the previously described roles of PKA and PKC in facilitation, CaMKII also may be involved.
). It is not known whether KN-62 affects Ca2+/CaM-dependent adenylyl cyclase, however. Nor have biochemical studies been performed to examine its specificity in Aplysia. Indirect evidence indicates that KN-62 does not affect PKA and PKC in Aplysia, however. For example, the 5-HT-induced increases in excitability of the sensory neurons are known to be predominately mediated by PKA (Baxter and Byrne 1990a; Klein et al. 1986). An activator of PKC can increase excitability (Sugita et al. 1992), but this effect appears due, at least in part, to a PKC-induced activation of cAMP levels (S. Sugita and J. H. Byrne, unpublished observation). In addition, the 5-HT-induced increases in spike duration are mediated mainly by the combined actions of PKA and PKC (Baxter and Byrne 1990a; Braha et al. 1993; Castellucci et al. 1982; Sugita et al. 1992). These actions also are not affected by KN-62. Although additional studies are needed, the present results raise the intriguing possibility that CaMKII plays a dual role in regulating synaptic efficacy and 5-HT-induced short-term facilitation in Aplysia.
for review). PKA and PKC seem to engage both spike-duration dependent and SDI processes whereasCaMKII does not. Although KN-62 increased the spike duration slightly, CaMKII does not appear to be necessary for 5-HT-induced spike broadening. CaMKII also does not appear to be necessary for the enhancement of excitability produced by 5-HT. These results suggest that CaMKII may play a role exclusively in SDI processes.
View this table:
TABLE 1.
Involvement of second messenger systems
in short-term effects of 5-HT
; Mercer et al. 1991). However, our observation that inhibitors of CaMKII and CaM have similar effects suggests that CaMKII is activated via CaM in Aplysia. Therefore, the most likely possibility is that CaMKII is activated through an increase in the level of intracellular Ca2+, triggered either by the inositol trisphosphate (IP3)-dependent Ca2+ release from intracellular stores (Fink et al. 1988; Sawada et al. 1989; Scholz et al. 1988) or by a second messenger-dependent modulation of membrane Ca2+ channels (Braha et al. 1993; Kuno and Gardner 1987).
; Emptage and Carew 1993; Montarolo et al. 1986; Zhang et al. 1997), and this facilitation is associated with enhanced excitability as well as structural changes in the sensory neurons (Bailey et al. 1992; Dale et al. 1987; Glanzman et al. 1990; Wu et al. 1995). Considerable evidence indicates a critical role for the cAMP/PKA cascade in this process (Bartsch et al. 1995; Bergold et al. 1990; Dash et al. 1990; O'Leary et al. 1995; Schacher et al. 1988; Scholz and Byrne 1988; Wu et al. 1995). Recently, we found that KN-62 did not affect either the initiation or the maintenance of long-term facilitation (Zhang et al. 1995), providing further support for the hypothesis that at least some of the actions of the kinases are segregated.
-CaMKII, paired pulse facilitation (PPF) is attenuated, but posttetanic facilitation (PTP) is enhanced (Chapman et al. 1995). These results suggest that CaMKII has a facilitatory role in one form of synaptic plasticity (PPF) but an inhibitory role in another form (PTP). In addition, excitatory synaptic currents were enhanced but PPF and PTP were reduced in transformed strains of Drosophila that express a specific inhibitor of CaM kinase (Wang et al. 1994). Our observation that a CaMKII inhibitor enhanced the amplitude of the EPSP and attenuated the 5-HT-induced facilitation also suggests a dual role for CaMKII in synaptic transmission.
, 1985). When bound to the membrane-cytoskeleton complex, CaMK may have tonic effects on the membrane currents that contribute to repolarization of the action potential. A block of CaMK at this locus would broaden the spike and enhance synaptic transmission. After treatment with 5-HT, CaMK is released from the membrane-cytoskeleton complex to the cytoplasm (Saitoh and Schwartz 1983, 1985). The free CaMK in the cytoplasm may have a facilitatory effect on synaptic transmission similar to that in the giant synapse of squid (Llinas et al. 1985). A block of CaMK at this locus would inhibit5-HT-induced facilitation. An alternative hypothesis is that the complex effects of CaM and CaMKII inhibitors arise from cross-talk among the multiple second messenger systems implicated in the plasticity at the sensorimotor synapse (e.g., Byrne et al. 1993). These interactions may occur at multiple levels, ranging from the receptors to substrate proteins.
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ACKNOWLEDGEMENTS |
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This work was supported by National Institutes of Health Research Grants R01 NS-28462 to A. Eskin and R01 NS-19895 and K05 MH-00649 to J. H. Byrne.
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FOOTNOTES |
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Address for reprint requests: J. H. Byrne, Dept. of Neurobiology and Anatomy, The University of Texas Medical School, PO Box 20708, Houston, TX 77225. E-Mail: jbyrne{at}nba19.med.uth.tmc.edu
Received 25 September 1996; accepted in final form 19 May 1997 .
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REFERENCES |
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Abstract
Introduction
Methods
Results
Discussion
References
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I. Jin and R. D. Hawkins Presynaptic and Postsynaptic Mechanisms of a Novel Form of Homosynaptic Potentiation at Aplysia Sensory-Motor Neuron Synapses J. Neurosci., August 13, 2003; 23(19): 7288 - 7297. [Abstract] [Full Text] [PDF]
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A. Angers, D. Fioravante, J. Chin, L. J. Cleary, A. J. Bean, and J. H. Byrne Serotonin Stimulates Phosphorylation of Aplysia Synapsin and Alters Its Subcellular Distribution in Sensory Neurons J. Neurosci., July 1, 2002; 22(13): 5412 - 5422. [Abstract] [Full Text] [PDF]
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S. Royer, R. L. Coulson, and M. Klein Switching Off and On of Synaptic Sites at Aplysia Sensorimotor Synapses J. Neurosci., January 15, 2000; 20(2): 626 - 638. [Abstract] [Full Text] [PDF]
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D. A. Baxter, C. C. Canavier, J. W. Clark Jr., and J. H. Byrne Computational Model of the Serotonergic Modulation of Sensory Neurons in Aplysia J Neurophysiol, December 1, 1999; 82(6): 2914 - 2935. [Abstract] [Full Text] [PDF]
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X.-Y. Jiang and T. W. Abrams Use-Dependent Decline of Paired-Pulse Facilitation at Aplysia Sensory Neuron Synapses Suggests a Distinct Vesicle Pool or Release Mechanism J. Neurosci., December 15, 1998; 18(24): 10310 - 10319. [Abstract] [Full Text] [PDF]
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 R E Zwartjes, H West, S Hattar, X Ren, F Noel, M Nunez-Regueiro, K MacPhee, R Homayouni, M T Crow, J H Byrne, et al. Identification of specific mRNAs affected by treatments producing long-term facilitation in Aplysia. Learn. Mem., January 1, 1998; 4(6): 478 - 495. [Abstract] [PDF]
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