| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1Department of Physiology, Kanazawa Medical University, Ishikawa; 2Department of Integrative Brain Science, Kyoto University Graduate School of Medicine, Kyoto; 3Medical Genetics Research Center, Nara Medical University, Nara; and 4Mitsubishi Kagaku Institute of Life Sciences (MITILS), Tokyo, Japan
Submitted 3 October 2007; accepted in final form 5 December 2007
 |
ABSTRACT |
|---|
|
|
|
INTRODUCTION |
|---|
|
; Berridge 1998; Verkhratsky 2005). These channels are often linked by scaffold proteins (Fagni et al. 2002; Kim and Sheng 2004) and function in such organized manners that opening of one class of channels causes sequential activation of another class of channels (Emptage et al. 1999; Isaacson and Murphy 2001; Nakamura et al. 1999; Yamada et al. 2004; Yamamoto et al. 2000, 2002a,b). However, it is not clear whether particular scaffold proteins actually organize such functional channel couplings.
A scaffold protein Homer/Vesl family is capable of binding to group I metabotropic glutamate receptors (mGluRs) (Brakeman et al. 1997), inositol-1,4,5-triphosphate receptors (IP3Rs) (Tu et al. 1998), ryanodine receptors (RyRs) (Feng et al. 2002; Westhoff et al. 2003), and transient receptor potential channels (TRPs) (Yuan et al. 2003) directly, and N-methyl-D-aspartate receptors (NMDARs) indirectly through Shank, another scaffolding protein (Sheng and Kim 2000). All those Homer-attachable channels or proteins are critically involved in synaptic plasticity. Since the first report that activation of group I mGluRs is required for LTD induction in rat visual cortex slices (Kato 1993), there have been numerous studies that have implicated the role of group I mGluRs in long-term synaptic plasticity. IP3Rs are reported to determine the magnitude and polarity of long-term potentiation (LTP) or long-term depression (LTD) (Kato et al. 2000; Nishiyama et al. 2000). RyRs seem to modulate the magnitude of LTD (Nakano et al. 2004) or LTP (Balschun et al. 1999; Futatsugi et al. 1999; Shimuta et al. 2001). Functional coupling between mGluRs and TRPs is reported to be critical in LTP induction (Topolnik et al. 2006). Thus the Homer proteins seem to be in a strategic position to orchestrate these channels and to regulate long-term synaptic plasticity.
Homer1a/Vesl-1S is a unique member of Homer family because it misses the dimerization motif required for linking two or more channels (Brakeman et al. 1997; Kato et al. 1997) and, for this reason, is thought to be a dominant-negative regulator of the other members of Homer, the long Homer proteins. Homer 1a is also shown to serve as an intracellular ligand for group I mGluRs (Ango et al. 2001). More interestingly, Homer 1a is activity-dependently expressed, whereas expression of long Homer proteins is constitutive. Homer 1a may therefore be expressed by plasticity-prone synaptic stimulation and involved in synaptic modification in diverse manners. In fact, both up- and downregulation of synaptic transmission by Homer 1a have been reported (Hennou et al. 2003; Kammermeier and Worley 2007; Sala et al. 2003; van Keuren-Jensen and Cline 2006). Furthermore, it has been recently reported that genetically overexpressed Homer 1a impaired hippocampal LTP (Celikel et al. 2007). On the other hand, roles played by Homer 1a in LTD, induced by synaptic stimulation, have not been well studied. The present experiments examined the effects of Homer 1a, injected and induced by electroconvulsive shock (ECS), on LTD in visual cortex slices, because LTD in this structure is regulated at least partly by the mGluR-IP3 signaling (Kato 1993; Kato et al. 2000).
|
|
METHODS |
|---|
|
All experiments were performed in accordance with the guiding principle of the Physiological Society of Japan and with the approval of the Animal Care Committee of Kanazawa Medical University. In brief, Wistar rats (15–19 days old) were decapitated under ether anesthesia. The brain was dissected out and soaked into high-sucrose containing medium composed of (in mM) 234 sucrose, 26 NaHCO3, 10 MgSO4, 2.5 KCl, 1.25 NaH2PO4, 0.5 CaCl2, and 11 glucose, bubbled with a mixture of 95% O2-5% CO2. Slices (250 µm thick) of the primary visual cortex were prepared with a Linearslicer PRO-7 or microslicer Zero-1 (Dosaka, Kyoto, Japan). Slices were kept at 30°C for 
60 min before experiments in normal artificial cerebrospinal fluid (ACSF) composed of (in mM) 124 NaCl, 3 KCl, 2.5 CaCl2, 2 MgSO4, 1.3 NaH2PO4, 26 NaHCO3, and 20 glucose, bubbled with a mixture of 95% O2-5% CO2.
Electroconvulsive shock (ECS)
Electrical stimulations were carried out basically as described previously (Sakagami et al. 2005; Yamamoto et al. 2005) with minor modifications. Brief single electrical shock (60 V, 1 s) was applied to the head through two electrodes placed on the ears, one on each side, and then the rats were returned to the cage. Seizure thereby elicited lasted for a minute, during which the whole body became spastic with the eyelids closed and the extremities rigidly flexed. Then the rats stayed immobile for minutes in a fixed position in the cage with the eyelids opened and the extremities relaxed. Ten minutes after the electrical shock, the rats looked normal. The rats were killed at 30 min after the shock, and the brains were removed immediately for slice cutting. Excitatory postsynaptic currents (EPSCs) were recorded from pyramidal cells within 5 h because expression level of Homer 1a protein was gradually increased during this period (Brakeman et al. 1997). In some experiments, stimulation of a lower intensity subthreshold to seizure (30 V, 1 s) was applied. A single electrical shock (sub-ECS; 30 V, 1 s) was applied. Rats were jumped and vocalization occurred, but seizure was not elicited. Soon after the electrical shock, the rats looked normal. The rats were killed at 30 min after the shock. EPSCs were recorded from pyramidal cells at 2–5 h after sub-ECS.
Electrophysiology
Slices were placed in a recording chamber on the stage of an upright microscope (Axioskop FS2, Zeiss, Germany) with a x63 water-immersion objective (Achroplan-63/0.9W, Zeiss). The chamber was continuously perfused with ACSF (30°C) bubbled with a mixture of 95% O2-5% CO2. For voltage-clamp experiments, we used patch pipettes (5–9 M
) filled with the internal solution containing (in mM) 130 Cs-methanesulfonate, 10 tetraethylammonium chloride, 0.2 EGTA, 5 QX-314 chloride, 10 HEPES, 2 Na2ATP, 0.4 Na2GTP, 2 MgCl2, and 10 CsCl, adjusted to pH 7.2–7.3 with CsOH. In some experiments, Homer proteins or anti-Homer antibodies were included in the pipette solution. Whole cell recording was made from layer II/III, V, or VI pyramidal cells of the primary visual cortex. Membrane potential was voltage-clamped at –70 mV (Axopatch 700A, Axon Instruments), and EPSCs were evoked by stimulation at 0.05 Hz using a bipolar tungsten electrode. A stimulation electrode was inserted into layer IV for recording from layer II/III and into layer II/III for recording from layer V or VI. Experiments were begun only after series resistance had stabilized (typically 15–35 M). Throughout the recording, series resistance was monitored continuously, and the recording was excluded from the data analysis if it varied by >20%. After a stable control level of EPSC was recorded for 5 min, LTD was induced by using a pairing protocol: 600 stimuli at 1 Hz were delivered under voltage-clamp at –40 mV.
Recombinant protein and antibody
Purified Homer1a/Vesl-1S protein (1 mg/ml) and rabbit polyclonal anti-Homer1a/Vesl-1S antibody were characterized as described previously (Kato et al. 1997, 1998, 2001).
Drugs used
Depending on the purpose of the experiments, D-2-amino-5- phosphonovaleric acid (D-APV, 50 µM; Tocris, Bristol, UK) or 2-methyl-6-(phenylethynyl)-pyridine (MPEP, 10 µM; Tocris) was bath-applied. Homer 1a protein (1 or 3 µg/ml), anti-Homer 1a antibody (0.4 µg/ml), or heparin (1 mg/ml; Nacalai, Kyoto, Japan) was contained in the pipette solution and distributed into the cell by diffusion.
Data analysis
Electrophysiological data were filtered at 5 kHz and digitized at 10 kHz (Digidata 1322A and pClamp8, Axon Instruments). For data analysis, pClamp9 (Axon Instruments) was used for calculating the amplitude of EPSCs, and three samples were averaged for each data point. EPSC amplitudes were normalized to baseline and expressed as averages ± SE. The magnitude of LTD was assessed by comparing the average amplitude of responses, obtained between 31 and 35 min after conditioning stimulation, with the preconditioning control. Paired or unpaired t-test were used for statistics with the significance level set at P < 0.05.
|
|
RESULTS |
|---|
|
EPSCs were recorded from layer VI pyramidal cells bathed in normal medium with or without Homer 1a protein injected. The presynaptic stimulation electrode was placed between layer II and III. In agreement with the previous data (Rao and Daw 2004), LTD was induced in control experiments without Homer 1a (61.1 ± 5.2%, n = 7; Fig. 1A). With Homer 1a injected by diffusion from patch pipettes (1 µg/ml), LTD magnitude at the late phase (22 min postpairing) was significantly reduced (79.4 ± 6.1%, n = 9; P < 0.03, 22 min postpairing; Fig. 1B). On the other hand, the baseline transmission was not changed even with Homer 1a injected (97.5 ± 12.6%, n = 4). We have previously reported that injection of Homer 1a protein elicited hyperpolarization of rat visual cortex pyramidal cells in layer II/III under current-clamp condition by using potassium-based internal solution. In that case, hyperpolarization progressed gradually and reached the steady state within 10 min after break-in (Sakagami et al. 2005), indicating that diffusion of Homer 1a must be completed within 10 min. We therefore started LTD induction 10 min after the whole cell break-in in the present study.
|
). Recently, it has been reported that LTD induced by 1-Hz presynaptic simulation of layer II/III paired with postsynaptic depolarization to –40 mV in layer VI of the rat visual cortex was dependent on group I mGluRs but not on NMDARs (Daw et al. 2004; Rao and Daw 2004). This finding was first confirmed in the present experiments. With the NMDAR antagonist D-APV bath-applied (50 µM), LTD was still induced (70.8 ± 4.6%, n = 6; Fig. 1C). On the other hand, bath application of MPEP (10 µM), a noncompetitive group I mGluR (mGluR5) antagonist, significantly suppressed LTD (83.8 ± 7.7%, n = 7; P < 0.03; Fig. 1D). Both subtypes of group I mGluRs, mGluR1 and mGluR5, are involved in group I mGluR-dependent long-term synaptic plasticity (Volk et al. 2006; Wang and Daw 2003). However, in pyramidal cells of the rat neocortex, the expression of mGluR5 is much more prominent than that of mGluR1 (Shigemoto et al. 1993). Furthermore, mGluR5 rather than mGluR1 seems to be preferentially associated with Homer-mediated signaling in the rat visual cortex (Yamamoto et al. 2005). We therefore used the mGluR5 antagonist MPEP as a representative group I mGluR antagonist. To check involvement of the IP3 signaling downstream of group I mGluRs, we examined the effect of IP3R blocker heparin on LTD in layer VI pyramidal cells. With heparin (1 mg/ml) injected by diffusion from patch pipettes, LTD was significantly suppressed (85.8 ± 6.8%, n = 7; P < 0.02; Fig. 1E). The dependence of layer VI LTD on the mGluR-IP3 signaling is consistent with its Homer 1a sensitivity because Homer 1a is known to modulate the mGluR-IP3 signaling by agonist-independent activation of mGluR (Ango et al. 2001; Yamamoto et al. 2005) or its dominant-negative effect on constitutive Homers (Fagni et al. 2002). LTD was insensitive to Homer 1a in layer II/III and layer V pyramidal cells
EPSCs were recorded from layer II/III pyramidal cells with or without Homer 1a injected. The presynaptic stimulation electrode was placed in layer IV. Without Homer 1a, LTD was induced in normal medium (60.9 ± 5.0%, n = 7; Fig. 2A). In contrast to the findings obtained from layer VI neurons, Homer 1a injection allowed induction of a comparable LTD (1 µg/ml, 56.1 ± 3.6%, n = 8; Fig. 2B). LTD of much the same amplitude was observed again with the triple concentration of Homer 1a (3 µg/ml, 55.8 ± 4.2%, n = 6; Fig. 2B), suggesting that the lack of Homer 1a effect was not due to low concentration. In layer II/III, LTD was significantly suppressed with bath application of D-APV (50 µM, 82.4 ± 5%, n = 9; P < 0.01; Fig. 2C). Bath application of MPEP (10 µM), on the other hand, failed to block LTD (54.0 ± 5.1%, n = 4; Fig. 2D).
|
|
The experiments so far suggest that Homer 1a could modulate mGluR-mediated LTD in layer VI. Although the mGluR antagonist MPEP or IP3R blocker heparin strongly suppressed LTD immediately after the induction protocol, the suppressing effect of injected Homer 1a slowly emerged and was not apparent at the earliest phase of LTD. Because intracellular distribution of injected Homer 1a protein was not visualized in our present study, we could not exclude the possibility that only a limited amount of Homer 1a was localized at synaptic sites at the earliest phase of LTD. To assure intracellular distribution of Homer 1a, we made use of ECS, a powerful experimental tool that has been confirmed to induce endogenous Homer 1a (Altar et al. 2004; Brakeman et al. 1997). Previous studies showed that activity-induced endogenous Homer 1a protein was accumulated in postsynaptic region (Kato et al. 2001). We thus examined whether ECS-induced Homer 1a, as well as Homer 1a injected from the pipette, alters neocortical LTD.
In slices obtained from ECS-subjected rats, LTD was significantly suppressed soon after pairing protocol in layer VI (90.2 ± 3.7%, n = 9; P < 0.001 as compared with the no-ECS control; Fig. 4A), although baseline transmission was not changed (86.5 ± 4.3%, n = 4). ECS triggers expression of not only Homer 1a, but a large number of gene products, some of which are thought to be involved in long-term synaptic plasticity (Altar et al. 2004). Previously, we reported that Homer 1a induced by ECS hyperpolarizes rat visual cortex pyramidal cells and upregulates L-type calcium channel currents under current-clamp mode with potassium-based internal solution and that both of these two Homer 1a effects were disrupted by co-application of anti-Homer 1a antibody (Sakagami et al. 2005; Yamamoto et al. 2005). We therefore checked the involvement of Homer 1a by using anti-Homer 1a antibody (0.4 µg/ml). In ECS-subjected tissue, the antibody injected through patch pipettes restored LTD (61.9 ± 8.3%, n = 5, not statistically different from the no-ECS control; Fig. 4B). However, rabbit IgG (0.4 µg/ml) injection failed to restore LTD (90.9 ± 9.5%, n = 4, not statistically different from just ECS cases), indicating that the effect of anti-Homer 1a antibody is not nonspecific. It was thus shown that the suppressing effect of ECS on LTD in layer VI was mediated at least partly by Homer 1a.
|
; Potschka et al. 2002). In slices from the sub-ECS group, significant LTD was still induced in layer VI pyramidal cells (66.9 ± 4.3%, n = 5, not statistically different from the no-ECS control; Fig. 4C). However, in contrast to the findings obtained from ECS group, the earliest phase of LTD appeared to be reduced. As we showed, LTD in layer II/III (Fig. 2B) or layer V pyramidal cells (Fig. 3B) was still induced with Homer 1a injection. Here we examined whether ECS could modify LTD in these layers. However, LTD was still induced in layer II/III (62.2 ± 4.2%, n = 4; Fig. 5A) and layer V pyramidal cells (66.9 ± 7.4%, n = 5; Fig. 5B) following ECS.
|
|
|
DISCUSSION |
|---|
|
Roles of Homer 1a on basal synaptic transmission
Homer 1a was initially characterized as a gene upregulated by tetanization leading to LTP (Kato et al. 1997). Subsequent studies have reported that Homer 1a both up- and downregulates glutamatergic synaptic responses in various preparations: suppression of AMPAR- and NMDAR-mediated synaptic transmission in rat hippocampal neurons through its protein-binding ability (Sala et al. 2003); facilitation of AMPAR-mediated synaptic transmission and clustering of synaptic AMPAR in rat hippocampal neurons (Hennou et al. 2003); reversal of group I mGluR-mediated up-regulation of AMPAR transmission in dark-reared tadpole tectal neurons (van Keuren-Jensen and Cline 2006); and restoration of group I mGluR-mediated EPSC decrease at hippocampal autaptic synapses (Kammermeier and Worley 2007). According to these results as well as a recently published review (Shiraishi-Yamaguchi and Furuichi 2007), AMPAR responses are considered to be both up- and downregulated by Homers interacting with mGluRs or other proteins, depending on experimental conditions such as activity states of recorded neurons or variation of extent in gene expression. In our present study, we used both protein injection and ECS application to induce Homer 1a expression. In both cases, we did not observe any marked changes in basal transmission in layer VI pyramidal cells, although LTD was modulated. Recently, it has reported that overexpression of Homer 1a inhibited LTP in the hippocampus (Celikel et al. 2007). Consistent with our study, they showed that basal transmission was unaffected by overexpression of Homer 1a. We cannot rule out short-term changes in synaptic transmission after Homer 1a expression because we began recording 5 to 10 min after break-in for diffusion of injected Homer 1a protein (Sakagami et al. 2005). Several recent studies have described effects of activity-induced Homer 1a in more physiological contexts: nociception (Tappe et al. 2006), visual experience (van Keuren-Jensen and Cline 2006), and seizure activity induced by ECS (Sakagami et al. 2005; Yamamoto et al. 2005; present study). These lines of investigation would provide further insights into mechanisms of Homer 1a action on basal synaptic responses.
Roles of Homer 1a on long-term synaptic modification
In contrast to action of Homer 1a on basal transmission, that on long-term synaptic modification remains unclear. Previous studies have reported involvement of constitutively expressed Homer, but not Homer 1a, proteins in LTD. First, impairment of mGluR-dependent LTD after status epilepticus was associated with decrease in expression levels of constitutive Homer and mGluR5 in the rat hippocampus but not that of Homer 1a (Kirschstein et al. 2007). Second, impairment of endocannabinoid-mediated LTD after cocaine administration was associated with increase in the expression level of constitutive Homer and decrease in surface expression of mGluR5 in the mouse nucleus accumbens (Fourgeaud et al. 2004). In both studies, changes in LTD or Homer expression were observed in chronic or subchronic conditions, in which just constitutive Homers would be in function or detectable. In contrast to constitutively expressed Homers, expression of the activity-induced Homer 1a was transient (Brakeman et al. 1997) and can last for only a few hours (Sakagami et al. 2005; Yamamoto et al. 2005). Our present experiments were done rather in acute conditions and demonstrated roles of injected and acute ECS-induced Homer 1a in LTD, thus shedding new light on roles of Homers in synaptic plasticity.
In the present study, the suppressing effect of Homer 1a on LTD was significant at the late phase of LTD (22 min postpairing). Similarly, a recent study has reported that overexpression of Homer 1a suppressed LTP at the late phase (20–25 min postpairing) in hippocampal CA1 neurons (Celikel et al. 2007). It is thus suggested that Homer 1a affects only a late phase of long-term modification of synaptic efficiency. On the other hand, effects of ECS on LTD were observed at both the early and late phases of LTD in the present experiments, suggesting that ECS interferes with the early phase of LTD by means of other mediators than Homer 1a. Indeed, after anti-Homer 1a antibody injection into pyramidal neurons in slices from ECS-subjected rats, LTD was restored only at the late phase. It would be interesting to look for the molecular identity of this early phase mediator. In this light, the present sub-ECS experiments may be suggestive, since sub-ECS suppressed only the early phase of LTD and left the late phase intact. Comparison between the two arrays of molecules expressed by ECS and sub-ECS might provide some cue for such a mediator or mediators.
Homer 1a as a feedback regulator of neural excitability
As we show in this paper, exogenously injected or ECS-induced Homer 1a significantly suppressed LTD in layer VI but not in layer II/III or layer V pyramidal cells. Homer 1a was detected in the pyramidal cells of all layers after ECS (Brakeman et al. 1997). Also, group I mGluRs are distributed throughout the cortical layers (Shigemoto et al. 1993). These observations and the present experiments, taken together, suggest that layer-specific effects of Homer 1a on group I mGluR-dependent LTD are not due to layer-specific expression of Homer 1a or group I mGluRs in the visual cortex. According to both anatomical and electrophysiological studies, corticothalamic efferents from the visual cortex to the lateral geniculate body originate exclusively from layer VI pyramidal cells (Kato et al. 1983, 1984). These corticothalamic feedback projections have been reported to sharpen receptive fields or increase filtering properties of visual thalamic neurons (Alitto and Usrey 2003; Cudeiro and Sillito 2006). According to the present results, Homer 1a induced by incoming visual activity would allow LTD induction in layers II/III and V but prevent it in layer VI, the output layer back to the lateral geniculate body. We propose that activity-dependently induced Homer 1a may downregulate cortical activities without drastically reducing corticothalamic feedback outputs and that such differential regulation may effectively fine tune the balance among thalamic, cortical, and thalamocortical activities.
Noninvasive strategy for the treatment of depressive disorders
For inducing endogenous Homer 1a expression, we carried out ECS as an experimental tool in this paper. It is well known that ECS is an experimental model of electroconvulsive therapy (ECT), which is a clinically efficient and trustworthy treatment for drug-resistant depressive disorders. However, convulsion necessitates anesthesiological care, and ECS could cause adverse effects such as memory loss (Squire et al. 1975). If neurobiological mechanisms of ECT effects became well understood, we could extract and exploit the essence of ECT for other forms of therapy that are based on neurobiological understanding of ECT but achieved by much less invasive methods. A recent microarray analysis has revealed that 
20 genes including Homer 1a are highly expressed by ECS (Altar et al. 2004). To date, Homer proteins have been implicated in memory, neuropsychiatric disorders and long-term synaptic plasticity (Celikel et al. 2007; Giuffrida et al. 2005; Szumlinski et al. 2006). We believe that to investigate physiological effects of Homers on neural behaviors including synaptic plasticity should contribute to understanding and extracting the neurobiological essence of ECT.
|
|
GRANTS |
|---|
|
|
|
ACKNOWLEDGMENTS |
|---|
|
|
|
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: N. Kato, Dept. of Physiology, Kanazawa Medical University, 920-0293 Ishikawa, Japan (E-mail: kato{at}kanazawa-med.ac.jp)
|
|
REFERENCES |
|---|
|
Altar CA, Laeng P, Jurata LW, Brockman JA, Lemire A, Bullard J, Bukhman YV, Young TA, Charles V, Palfreyman MG. Electroconvulsive seizures regulate gene expression of distinct neurotrophic signaling pathways. J Neurosci 24: 2667–2677, 2004.
Ango F, Prezeau L, Muller T, Tu JC, Xiao B, Worley PF, Pin JP, Bockaert J, Fagni L. Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer. Nature 411: 962–965, 2001.[CrossRef][Medline]
Anwyl R. Induction and expression mechanisms of postsynaptic NMDA receptor-independent homosynaptic long-term depression. Prog Neurobiol 78: 17–37, 2006.[CrossRef][Web of Science][Medline]
Balschun D, Wolfer DP, Bertocchini F, Barone V, Conti A, Zuschratter W, Missiaen L, Lipp HP, Frey JU, Sorrentino V. Deletion of the ryanodine receptor type 3 (RyR3) impairs forms of synaptic plasticity and spatial learning. EMBO J 18: 5264–5273, 1999.[CrossRef][Web of Science][Medline]
Berridge MJ. Neuronal calcium signaling. Neuron 21: 13–26, 1998.[CrossRef][Web of Science][Medline]
Brakeman PR, Lanahan AA, O'Brien R, Roche K, Barnes CA, Huganir RL, Worley PF. Homer: a protein that selectively binds metabotropic glutamate receptors. Nature 386: 284–288, 1997.[CrossRef][Medline]
Celikel T, Marx V, Freudenberg F, Zivkovic A, Resnik E, Hasan MT, Licznerski P, Osten P, Rozov A, Seeburg PH, Schwarz MK. Select overexpression of Homer1a in dorsal hippocampus impairs spatial working memory. Front Neurosci 1: 97–110, 2007.
Cudeiro J, Sillito AM. Looking back: corticothalamic feedback and early visual processing. Trends Neurosci 29: 298–306, 2006.[CrossRef][Web of Science][Medline]
Daw N, Rao Y, Wang XF, Fischer Q, Yang Y. LTP and LTD vary with layer in rodent visual cortex. Vision Res 44: 3377–3380, 2004.[CrossRef][Web of Science][Medline]
Emptage N, Bliss TV, Fine A. Single synaptic events evoke NMDA receptor-mediated release of calcium from internal stores in hippocampal dendritic spines. Neuron 22: 115–124, 1999.[CrossRef][Web of Science][Medline]
Fagni L, Worley PF, Ango F. Homer as both a scaffold and transduction molecule. Sci STKE 137: RE8, 2002.
Feng W, Tu J, Yang T, Vernon PS, Allen PD, Worley PF, Pessah IN. Homer regulates gain of ryanodine receptor type 1 channel complex. J Biol Chem 277: 44722–44730, 2002.
Fourgeaud L, Mato S, Bouchet D, Hemar A, Worley PF, Manzoni OJ. A single in vivo exposure to cocaine abolishes endocannabinoid-mediated long-term depression in the nucleus accumbens. J Neurosci 24: 6939–6945, 2004.
Futatsugi A, Kato K, Ogura H, Li ST, Nagata E, Kuwajima G, Tanaka K, Itohara S, Mikoshiba K. Facilitation of NMDAR-independent LTP and spatial learning in mutant mice lacking ryanodine receptor type 3. Neuron 24: 701–713, 1999.[CrossRef][Web of Science][Medline]
Giuffrida R, Musumeci S, D'Antoni S, Bonaccorso CM, Giuffrida-Stella AM, Oostra BA, Catania MV. A reduced number of metabotropic glutamate subtype 5 receptors are associated with constitutive homer proteins in a mouse model of fragile X syndrome. J Neurosci 25: 8908–8916, 2005.
Hennou S, Kato A, Schneider EM, Lundstrom K, Gahwiler BH, Inokuchi K, Gerber U, Ehrengruber MU. Homer-1a/Vesl-1S enhances hippocampal synaptic transmission. Eur J Neurosci 18: 811–819, 2003.[CrossRef][Web of Science][Medline]
Isaacson JS, Murphy GJ. Glutamate-mediated extrasynaptic inhibition: direct coupling of NMDA receptors to Ca2+-activated K+ channels. Neuron 31: 1027–1034, 2001.[CrossRef][Web of Science][Medline]
Kammermeier PJ, Worley PF. Homer 1a uncouples metabotropic glutamate receptor 5 from postsynaptic effectors. Proc Natl Acad Sci USA 104: 6055–6060, 2007.
Kato A, Fukuda T, Fukazawa Y, Isojima Y, Fujitani K, Inokuchi K, Sugiyama H. Phorbol esters promote postsynaptic accumulation of Vesl-1S/Homer-1a protein. Eur J Neurosci 13: 1292–1302, 2001.[CrossRef][Web of Science][Medline]
Kato A, Ozawa F, Saitoh Y, Hirai K, Inokuchi K. vesl, a gene encoding VASP/Ena family related protein, is upregulated during seizure, long-term potentiation and synaptogenesis. FEBS Lett 412: 183–189, 1997.[CrossRef][Web of Science][Medline]
Kato A, Ozawa F, Saitoh Y, Fukazawa Y, Sugiyama H, Inokuchi K. Nobel members of the vesl/Homer family of PDZ proteins that bind metabotropic glutamate receptors. J Biol Chem 273: 23969–23975, 1998.
Kato N. Dependence of long-term depression on postsynaptic metabotropic glutamate receptors in visual cortex. Proc Natl Acad Sci USA 90: 3650–3654, 1993.
Kato N, Kawaguchi S, Miyata H. Geniculocortical projection to layer I of area 17 in kittens: orthograde and retrograde HRP studies. J Comp Neurol 225: 441–447, 1984.[CrossRef][Web of Science][Medline]
Kato N, Kawaguchi S, Yamamoto T, Samejima A, Miyata H. Postnatal development of the geniculocortical projection in the cat: electrophysiological and morphological studies. Exp Brain Res 51: 65–72, 1983.[Web of Science][Medline]
Kato N, Isomura Y, Tanaka T. Intracellular calcium releases facilitate induction of long-term depression. Neuropharmacology 39: 1107–1110, 2000.[CrossRef][Web of Science][Medline]
Kim E, Sheng M. PDZ domain proteins of synapses. Nat Rev Neurosci 5: 771–781, 2004.[CrossRef][Web of Science][Medline]
Kirschstein T, Bauer M, Muller L, Ruschenschmidt C, Reitze M, Becker AJ, Schoch S, Beck H. Loss of metabotropic glutamate receptor-dependent long-term depression via downregulation of mGluR5 after status epilepticus. J Neurosci 27: 7696–7704, 2007.
Nakamura T, Barbara JG, Nakamura K, Ross WN. Synergistic release of Ca2+ from IP3-sensitive stores evoked by synaptic activation of mGluRs paired with backpropagating action potentials. Neuron 24: 727–737, 1999.[CrossRef][Web of Science][Medline]
Nakano M, Yamada S, Udagawa R, Kato N. Frequency-dependent requirement for calcium store-operated mechanisms in induction of homosynaptic long-term depression at hippocampus CA1 synapses. Eur J Neurosci 19: 2881–2887, 2004.[CrossRef][Web of Science][Medline]
Nishiyama M, Hong K, Mikoshiba K, Poo MM, Kato K. Calcium stores regulate the polarity and input specificity of synaptic modification. Nature 408: 584–588, 2000.[CrossRef][Medline]
Oliet SH, Malenka RC, Nicoll RA. Two distinct forms of long-term depression coexist in CA1 hippocampal pyramidal cells. Neuron 18: 969–982, 1997.[CrossRef][Web of Science][Medline]
Potschka H, Krupp E, Ebert U, Gumbel C, Leichtlein C, Lorch B, Pickert A, Kramps S, Young K, Grune U, Keller A, Welschof M, Vogt G, Xiao B, Worley PF, Loscher W, Hiemisch H. Kindling-induced overexpression of Homer 1A and its functional implications for epileptogenesis. Eur J Neurosci 16: 2157–2165, 2002.[CrossRef][Web of Science][Medline]
Rao Y, Daw NW. Layer variations of long-term depression in rat visual cortex. J Neurophysiol 92: 2652–2658, 2004.
Sakagami Y, Yamamoto K, Sugiura S, Inokuchi K, Hayashi T, Kato N. Essential roles of Homer-1a in homeostatic regulation of pyramidal cell excitability: a possible link to clinical benefits of electroconvulsive shock. Eur J Neurosci 21: 3229–3239, 2005.[CrossRef][Web of Science][Medline]
Sala C, Futai K, Yamamoto K, Worley PF, Hayashi Y, Sheng M. Inhibition of dendritic spine morphogenesis and synaptic transmission by activity-inducible protein Homer1a. J Neurosci 23: 6327–6337, 2003.
Sheng M, Kim E. The Shank family of scaffold proteins. J Cell Sci 113: 1851–1856, 2000.[Abstract]
Shigemoto R, Nomura S, Ohishi H, Sugihara H, Nakanishi S, Mizuno N. Immunohistochemical localization of a metabotropic glutamate receptor, mGluR5, in the rat brain. Neurosci Lett 163: 53–57, 1993.[CrossRef][Web of Science][Medline]
Shimuta M, Yoshikawa M, Fukaya M, Watanabe M, Takeshima H, Manabe T. Postsynaptic modulation of AMPA receptor-mediated synaptic responses and LTP by the type 3 ryanodine receptor. Mol Cell Neurosci 17: 921–930, 2001.[CrossRef][Web of Science][Medline]
Shiraishi-Yamaguchi Y, Furuichi T. The Homer family proteins. Genome Biol 8: 206, 2007.[CrossRef][Medline]
Squire LR, Slater PC, Chace PM. Retrograde amnesia: temporal gradient in very long term memory following electroconvulsive therapy. Science 187: 77–79, 1975.
Szumlinski KK, Kalivas PW, Worley PF. Homer proteins: implications for neuropsychiatric disorders. Curr Opin Neurobiol 16: 251–257, 2006.[CrossRef][Web of Science][Medline]
Tappe A, Klugmann M, Luo C, Hirlinger D, Agarwal N, Benrath J, Ehrengruber MU, During MJ, Kuner R. Synaptic scaffolding protein Homer1a protects against chronic inflammatory pain. Nat Med 12: 677–681, 2006.[CrossRef][Web of Science][Medline]
Topolnik L, Azzi M, Morin F, Kougioumoutzakis A, Lacaille JC. mGluR1/5 subtype-specific calcium signaling and induction of long-term potentiation in rat hippocampal oriens/alveus interneurons. J Physiol 575: 115–131, 2006.
Tu JC, Xiao B, Yuan JP, Lanahan AA, Leoffert K, Li M, Linden DJ, Worley PF. Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors. Neuron 21: 717–726, 1998.[CrossRef][Web of Science][Medline]
van Keuren-Jensen K, Cline HT. Visual experience regulates metabotropic glutamate receptor-mediated plasticity of AMPA receptor synaptic transmission by Homer1a induction. J Neurosci 26: 7575–7580, 2006.
Verkhratsky A. Physiology and pathophysiology of the calcium store in the endoplasmic reticulum of neurons. Physiol Rev 85: 201–279, 2005.
Volk LJ, Daly CA, Huber KM. Differential roles for group 1 mGluR subtypes in induction and expression of chemically induced hippocampal long-term depression. J Neurophysiol 95: 2427–2438, 2006.
Wang XF, Daw NW. Long term potentiation varies with layer in rat visual cortex. Brain Res 989: 26–34, 2003.[CrossRef][Web of Science][Medline]
Westhoff JH, Hwang SY, Duncan RS, Ozawa F, Volpe P, Inokuchi K, Koulen P. Vesl/Homer proteins regulate ryanodine receptor type 2 function and intracellular calcium signaling. Cell Calcium 34: 261–269, 2003.[CrossRef][Web of Science][Medline]
Yamada S, Takechi H, Kanchiku I, Kita T, Kato N. Small-conductance Ca2+-dependent K+ channels are the target of spike-induced Ca2+ release in a feedback regulation of pyramidal cell excitability. J Neurophysiol 91: 2322–2329, 2004.
Yamamoto K, Hashimoto K, Isomura Y, Shimohama S, Kato N. An IP3-assisted form of Ca2+-induced Ca2+ release in neocortical neurons. Neuroreport 11: 535–539, 2000.[Web of Science][Medline]
Yamamoto K, Hashimoto K, Nakano M, Shimohama S, Kato N. A distinct form of calcium release down-regulates membrane excitability in neocortical pyramidal cells. Neuroscience 109: 665–676, 2002a.[CrossRef][Web of Science][Medline]
Yamamoto K, Nakano M, Hashimoto K, Shimohama S, Kato N. Emergence of a functional coupling between inositol-1,4,5-triphosphate receptors and calcium channels in developing neocortical neurons. Neuroscience 109: 677–685, 2002b.[CrossRef][Web of Science][Medline]
Yamamoto K, Sakagami Y, Sugiura S, Inokuchi K, Shimohama S, Kato N. Homer 1a enhances spike-induced calcium influx via L-type calcium channels in neocortex pyramidal cells. Eur J Neurosci 22: 1338–1348, 2005.[CrossRef][Web of Science][Medline]
Yuan JP, Kiselyov K, Shin DM, Chen J, Shcheynikov N, Kang SH, Dehoff MH, Schwarz MK, Seeburg PH, Muallem S, Worley PF. Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors. Cell 114: 777–789, 2003.[CrossRef][Web of Science][Medline]
This article has been cited by other articles:
|
|
 |
|
  P. J. Kammermeier Endogenous Homer Proteins Regulate Metabotropic Glutamate Receptor Signaling in Neurons J. Neurosci., August 20, 2008; 28(34): 8560 - 8567. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
TOP
ABSTRACT
INTRODUCTION
; 3 µg/ml, 
) was unable to affect LTD. C: LTD was suppressed by bath-application of NMDAR antagonist D-APV (50 µM). D: LTD magnitude was unchanged in the presence of MPEP (10 µM). E: summary diagram describing averages of EPSC amplitudes in various experimental conditions. Error bars represent SE. *P < 0.01. Scale bars, 20 ms and 100 pA.
