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REPORT
Department of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, Basel, Switzerland
Submitted 6 July 2007; accepted in final form 19 September 2007
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ABSTRACT |
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-Aminobutyric acid type B (GABAB) receptors are known to regulate the main output neurons of the thalamus, the thalamocortical relay (TCR) cells. However, the contributions of the two predominant GABAB-receptor subtypes, GABAB(1a,2) and GABAB(1b,2), to the control of TCR cell activity are unknown. Here, we used genetic and electrophysiological methods to investigate subtype-specific GABAB effects at the inputs to TCR cells. We found that mainly GABAB(1a,2) receptors inhibit the release of glutamate from corticothalamic fibers impinging onto TCR cells. In contrast, both GABAB(1a,2) and GABAB(1b,2) receptors efficiently inhibit the release of GABA from thalamic reticular nucleus (TRN) neurons onto TCR neurons. Likewise, both GABAB(1a,2) and GABAB(1b,2) receptors efficiently activate somatodendritic K+ currents in TCR cells. In summary, our data show that GABAB(1b,2) receptors cannot compensate for the absence of GABAB(1a,2) receptors at glutamatergic inputs to TCR cells. This shows that the predominant association of GABAB(1a,2) receptors with glutamatergic terminals is a feature that is preserved at several brain synapses. Furthermore, our data indicate that the cognitive deficits observed with mice lacking GABAB(1a,2) receptors could to some extent relate to attention deficits caused by disinhibited release of glutamate onto TCR neurons. |
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INTRODUCTION |
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). The latter are thought to be involved in focusing attention onto particular sensory stimuli (Cudeiro and Sillito 2006). Feedforward (somatofugal) inhibition onto TCR cells is largely mediated by local interneurons, whereas feedback (corticofugal) inhibition originates from the thalamic reticular nucleus (TRN). TRN neurons in turn can be excited by either thalamic or cortical inputs. The relative balance of excitatory and inhibitory influences onto TCR cells largely determines their output, which is thought to be important for signal processing and attention mechanisms.
It is well known that -aminobutyric acid type B (GABAB) receptors regulate the excitability of TCR cells, but it remains unclear which receptor subtypes are associated with pre- and postsynaptic sites (Crunelli and Leresche 1991; Gervasi et al. 2003; Lee et al. 1994; Ulrich and Huguenard 1996). GABAB receptors are heteromeric complexes composed of GABAB1 and GABAB2 subunits (Bettler et al. 2004). Receptor heterogeneity results from the two subunit isoforms GABAB1a and GABAB1b, both of which combine with GABAB2 to form functional receptors. Presynaptically, GABAB receptors are known to inhibit the release of GABA (autoreceptors) and other neurotransmitters (heteroreceptors). Postsynaptically, GABAB receptors generate a late inhibitory postsynaptic potential (IPSP) by activation of Kir3-type K+ channels (Lüscher et al. 1997). GABAB(1a,2) and GABAB(1b,2) receptors exhibit no pharmacological or functional differences when expressed in heterologous cells. However, studies using mice lacking GABAB1a or GABAB1b subunits, here referred to as 1a–/– and 1b–/– mice, revealed that GABAB-receptor subtypes localize to distinct synaptic sites in the amygdala, cortex, and hippocampus (Perez-Garci et al. 2006; Shaban et al. 2006; Ulrich and Bettler 2007; Vigot et al. 2006). An emerging feature of GABAB receptor compartmentalization is the predominant association of GABAB(1a,2) receptors with glutamatergic boutons. Similarly, GABAB(1a,2) receptors are present at GABAergic terminals in the neocortex (Perez-Garci et al. 2006), but both GABAB(1a,2) and GABAB(1b,2) receptors localize to GABAergic terminals in the amygdala and hippocampus (Shaban et al. 2006; Vigot et al. 2006). Postsynaptic GABAB responses in the hippocampus and neocortex are largely mediated by GABAB(1b,2) receptors, whereas both receptor subtypes activate postsynaptic Kir3 channels in the amygdala to a similar extent. Consistent with unique in vivo functions for GABAB-receptor subtypes, it was shown that 1a–/– and 1b–/– mice exhibit selective deficits in learning and memory tasks (Jacobson et al. 2006; Shaban et al. 2006; Vigot et al. 2006).
To address the role of GABAB-receptor subtypes in the intrathalamic circuitry we compared pre- and postsynaptic GABAB responses in the somatosensory thalamus of wild-type (WT), 1a–/–, and 1b–/– mice. The results reveal that the two receptor subtypes coexist to a similar degree at postsynaptic sites and GABAergic terminals, but not at glutamatergic terminals. We discuss the implications of our findings for GABAB-receptor physiology in general and for thalamic physiology in particular.
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METHODS |
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). All animal experiments were approved by the veterinary office of Basel-Stadt. Mice of either sex (P16–P21) were anesthetized with isoflurane and horizontal slices (250 µm) were cut on a vibratome (Micron, Walldorf, Germany) in 5°C cold slicing solution containing (in mM): 234 sucrose, 11 glucose, 24 NaHCO3, 2.5 KCl, 1.25 NaH2PO4, 10 MgSO4, and 0.5 CaCl2, equilibrated with 95% O2-5% CO2.. Slices were kept in an incubator containing standard artificial cerebrospinal fluid (ACSF; see following text) at 32°C for 1 h before recordings. Whole cell patch-clamp recordings were performed under visual control (Stuart et al. 1993). Brain slices were transferred into a recording chamber and superfused (1 ml/min, 34°C) with standard ACSF containing (in mM): 126 NaCl, 26 NaHCO3, 2.5 KCl, 1.25 NaH2PO4, 2 MgSO4, 2 CaCl2, and 10 glucose, equilibrated with 95% O2-5% CO2. Patch pipettes were pulled from borosilicate glass (Harvard Instruments, Edenbridge, UK) and filled with a solution containing (in mM): 130 Cs-gluconate (or K-gluconate), 5 NaCl, 10 HEPES, 5 ATP, 0.5 GTP, and 1 EGTA (pH = 7.3, osmolarity = 290 mosmol). A liquid junction potential of –10 mV was left uncorrected. Current- and voltage-clamp recordings were obtained with an Axoclamp 2A amplifier (Molecular Devices, Union City, CA). Access resistance (5–15 M
) was monitored throughout the experiment and unstable recordings were disregarded. Composite inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs, respectively) were evoked by constant-current pulses (0.1 ms, 50–500 µA) by platinum/iridium electrodes (FHC, Bowdoin, ME) with a stimulus isolator (WPI, Sarasota, FL). Current and voltage traces were digitized at 3 kHz with a Digidata 1200A A/D converter (Molecular Devices). All drugs were from Tocris (Bristol, UK) and applied by the perfusate. IPSC and EPSC amplitudes were determined by subtracting 3- to 5-ms time-averaged baseline current segments from the IPSC or EPSC peak current. Data are presented as means ± SD and n designates the number of cells. |
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RESULTS |
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; 1a–/–: 179 ± 61 M; 1b–/–: 131 ± 46 M), and membrane time constant (WT: 19 ± 5.5 ms; 1a–/–: 19 ± 6.9 ms; 1b–/–: 17 ± 7.3 ms) were not significantly different between the three genotypes. We found that TCR cells exhibit a clear sag in the hyperpolarizing voltage trajectory in all genotypes (Fig. 3). Because the sag-mediating h-current in TCR cells is strongly modulated by cyclic adenosine monophosphate (cAMP) (Frère and Lüthi 2003), this result indicates that cAMP levels, which can be down-regulated by GABAB receptors, remain similar in all gentoypes. Additionally, neurons from all genotypes were capable of generating rebound burst firing (Fig. 3).
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). Individual TCR cells were voltage clamped at –60 mV and postsynaptic GABAB-mediated K+-channel responses blocked by intracellular Cs+ application (130 mM; Gähwiler and Brown 1985). EPSCs were small and of slow kinetics, reflecting their origin from distal dendrites, which is in line with the known localization of the corticothalamic inputs (Sherman and Guillery 1996). In WT mice bath application of the GABAB-receptor agonist baclofen (25 µM) significantly reduced the EPSC amplitudes from –31 ± 12 to –13 ± 9 pA (n = 6 cells, P < 0.02, paired t-test). This reduction was reversed by application of the GABAB-receptor antagonist 3-[[[(3,4-dichlorophenyl)methyl]-amino]propyl] diethoxymethyl phosphinic acid (CGP52432, 1 µM; Fig. 1, A–C). The EPSCs were always fully blocked by application of the 
-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX, 20 µM) and amino-phosphonovaleric acid (APV, 50 µM), respectively, demonstrating that the EPSCs were purely glutamatergic (Fig. 1, A–C). In contrast to the WT mice, the EPSC amplitudes in the 1a–/– mice were not significantly different in the presence or absence of baclofen (P > 0.1, n = 11 cells). However, in the 1b–/– mice the EPSC amplitude was significantly reduced in the presence of baclofen (P < 0.0005, n = 8 cells). One-way ANOVA confirmed that the effects of baclofen on presynaptic inhibition of EPSC amplitudes were significantly different between genotypes [WT: 58 ± 19%, 1a–/–: 36 ± 11%, 1b–/–: 75 ± 17%; F(2,22) = 15.78, P < 0.0001]. Post hoc comparisons between the genotypes revealed significant differences between WT and 1a–/– mice (P < 0.05) as well as between 1a–/– and 1b–/– mice (P < 0.001, Dunn test). In contrast, no significant differences were seen between WT and 1b–/– mice (Fig. 1D). This shows that GABAB-mediated inhibition of glutamate release at corticothalamic fibers is predominantly mediated by GABAB(1a,2) receptors.
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). Cells were voltage clamped at –20 mV to increase the driving force for chloride. The recording solution contained Cs+ to block postsynaptic GABAB responses by inhibiting K+ channels (Gähwiler and Brown 1985). Bath application of the GABAB-receptor agonist baclofen led to a significant reduction of the IPSC amplitudes by about 70% and this reduction was reversed by the GABAB-receptor antagonist CGP52432 (Fig. 2, A–C). The complete block of IPSCs by bicuculline at the end of the recordings confirmed that the IPSCs were mediated by GABAA receptors (Fig. 2, A–C). IPSC amplitude reduction by GABAB receptors was not significantly different between WT (73 ± 23%, n = 6 cells), 1a–/– (71 ± 15%, n = 6), and 1b–/– (71 ± 13%, n = 6) mice (Fig. 2D). This supports that GABAB(1a,2) and GABAB(1b,2) receptors both act as autoreceptors in this inhibitory cell type.
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Slow and prolonged GABAB-receptor–mediated IPSPs in TCR cells play an important role in generating rebound excitation. We investigated postsynaptic GABAB responses in TCR cells by adding baclofen (50 µM) to the perfusate for 2 min (Fig. 3, A–C). Membrane potential and input resistance were monitored with a K+-based recording solution. Baclofen induced a small hyperpolarization of a few millivolts that was not significantly different between WT (–3.1 ± 1 mV, n = 8 cells), 1a–/– (–2.5 ± 1 mV, n = 6), and 1b–/– mice (–3.4 ± 2.3 mV, n = 7) (Fig. 3D). This hyperpolarization was associated with a decrease in input resistance as assessed by small hyperpolarizing current pulses. Statistical comparison revealed that the baclofen-induced relative decrease in input resistance was similar for all genotypes (WT: 35 ± 10%, n = 8 cells; 1a–/–: 23 ± 8%, n = 6; 1b–/–: 29 ± 9%, n = 6; ordinary one-way ANOVA).
In summary, our electrophysiological recordings in the thalamus reveal a nonredundant functional role of GABAB(1a,2) receptors at glutamatergic terminals, whereas GABAB(a1,2) and GABAB(1b,2) receptors at GABAergic terminals and postsynaptic sites independently mediate full inhibition.
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DISCUSSION |
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; Vigot et al. 2006) and shows that the preferential association of GABAB(1a,2) receptors with glutamatergic terminals is a common feature. This predominance is interesting from a mechanistic perspective. The only regions of sequence divergence between GABAB1a and GABAB1b subunits are two extracellular "sushi domains" that are unique to GABAB1a (Ulrich and Bettler 2007). The sushi domains are evolutionarily conserved protein-interaction motifs. It is therefore reasonable to assume that they bind to protein(s) that are necessary for the localization of GABAB1a at glutamatergic terminals. The GABAB1a subunit is individually regulated at the transcriptional level (Steiger at al. 2004), which, in principle, allows dynamic adjustment of the level of presynaptic inhibition at glutamatergic synapses. A small but nonsignificant baclofen-induced inhibition of EPSC amplitudes of about 30% was observed in 1a–/– mice, similar to previous studies (Shaban et al. 2006; Vigot et al. 2006). This remaining inhibition may reflect the presence of a small amount of GABAB(1b,2) receptors at excitatory terminals. Possibly, the significant up-regulation of GABAB1b protein in the 1a–/– mice contributes to this remaining inhibition (Vigot et al. 2006). However, functional heteroreceptors in 1a–/– mice may also reflect that the mechanism leading to a dendritic distribution of GABAB1b is not absolute. The fact that baclofen-induced EPSC inhibition remains normal in 1b–/– mice further suggests a high receptor reserve and supports that GABAB-receptor subtypes do not interact linearly with presynaptic effector systems. The physiological conditions under which presynaptic GABAB receptors at corticothalamic fiber terminals become activated are not known (Nyitrai et al. 1996). However, it is assumed that reticular cells, which inhibit TCR neurons by lateral inhibition, are the source of the GABA involved in the activation of heteroreceptors (Deschênes et al. 2005). Thus attention may be enhanced by lateral presynaptic inhibition of out-of-focus corticothalamic feedback. An unhindered release of glutamate onto TCR neurons may therefore contribute to the cognitive impairments seen with 1a–/– mice (Jacobson et al. 2006; Shaban et al. 2006; Vigot et al. 2006).
We found that GABAB(1a,2) and GABAB(1b,2) receptors inhibit GABA release onto TCR cells to a similar extent. Likewise, autoreceptor function in the amygdala and the hippocampus was found to be mediated by both receptor subtypes (Shaban et al. 2006; Vigot et al. 2006). In contrast, the GABAB(1a,2)-receptor subtype exclusively conveyed autoreceptor function in the supragranular layers of the neocortex (Perez-Garci et al. 2006). This finding raised the possibility that different types of interneurons exclusively express one or the other subtype of GABAB receptors. However, reticular neurons are traditionally considered a homogeneous cell population (Ohara and Lieberman 1985) and local interneurons are absent in the rodent somatosensory thalamus (Barbaresi et al. 1986). Our findings in the thalamus therefore support that GABAB(1a,2) and GABAB(1b,2) receptors are coexpressed in individual inhibitory neurons and that individual receptor subtypes are sufficient to meditate autoreceptor function to its full extent. Alternatively, TRN neurons may consist of more than a single cell type (e.g., Spreafico et al. 1991), which could express one or the other receptor subtype at their terminals. Although the existence of GABAB autoreceptors on the terminals of TRN cells was also demonstrated in earlier electrophysiological experiments (Le Feuvre et al. 1997; Ulrich and Huguenard 1996), a recent morphological study failed to detect GABAB subunits at these structures (Kulik et al. 2002). In this context it is important to note that it has been generally difficult to demonstrate the existence of autoreceptors using immunohistochemical or ultrastructural techniques (Bettler et al. 2004). This probably reflects that the level of GABAB-autoreceptor expression is below the detection limit of immunochemical methods. It therefore appears that near GABA release sites few GABAB autoreceptors are sufficient to efficiently inhibit neurotransmitter release. It remains puzzling why electrophysiological recordings show a nonredundant functional role of GABAB(1a,2) receptors at glutamatergic terminals only. In addition to differences in expression and distribution it cannot be ruled out that the mode of presynaptic inhibition is different for GABAB-receptor subtypes and that this contributes to the observed differences between glutamatergic and GABAergic terminals. In that context it was shown that GABAB receptors can inhibit the release machinery independent of their effects on Ca2+ channels (Sakaba et al. 2003).
GABAB(1a,2) and GABAB(1b,2) receptors activate postsynaptic K+ channels in TCR neurons equally well (Fig. 3). GABAB(1a,2) receptors therefore significantly contribute to K+ channel activation and rebound burst firing. This may contribute to the development of absence-type seizures in transgenic mice overexpressing GABAB(1a,2) receptors (Wu et al. 2007). Efficient coupling of both receptor subtypes to postsynaptic effectors was also observed in pyramidal neurons of the amygdala (Shaban et al. 2006). In contrast, predominantly GABAB(1b,2) receptors activate K+-current responses in hippocampal pyramidal neurons (Vigot et al. 2006). The origin of this cell-type and receptor-subtype specific difference in the efficiency of receptor–effector coupling is unclear. Differences could, for example, result from a cell-type–specific variability in the expression levels of receptor subtypes. Moreover, differences in the distribution of receptor subtypes and effector K+ channels could result in a more or less efficient receptor–effector coupling. In this context it is interesting to note that GABAB1b but not GABAB1a localizes to dendritic spines in hippocampal neurons, which may provide the basis for differences in effector coupling (Vigot et al. 2006).
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GRANTS |
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ACKNOWLEDGMENTS |
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Present address of D. Ulrich: School of Medicine, Department of Physiology, Trinity College Dublin, Dublin 2, Ireland.
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FOOTNOTES |
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Address for reprint requests and other correspondence: D. Ulrich, School of Medicine, Department of Physiology, Trinity College Dublin, Dublin 2, Ireland (E-mail: ulrichd{at}tcd.ie)
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REFERENCES |
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Bettler B, Kaupmann K, Mosbacher J, Gassmann M. Molecular structure and physiological functions of GABA(B) receptors. Physiol Rev 84: 835–867, 2004.
Crunelli V, Leresche N. A role for GABAB receptors in excitation and inhibition of thalamocortical cells. Trends Neurosci 14: 16–21, 1991.[CrossRef][Web of Science][Medline]
Cudeiro J, Sillito AM. Looking back: corticothalamic feedback and early visual processing. Trends Neurosci 29: 298–306, 2006.[CrossRef][Web of Science][Medline]
Deschênes M, Timofeeva E, Lavallee P, Dufresne C. The vibrissal system as a model of thalamic operations. Prog Brain Res: 149: 31–40, 2005.
Frère SGA, Lüthi A. Pacemaker channels in mouse thalamocortical neurons are regulated by distinct pathways of cAMP synthesis. J Physiol 554: 111–125, 2003.
Gähwiler BH, Brown DA. GABAB-receptor-activated K+ current in voltage-clamped CA3 pyramidal cells in hippocampal cultures. Proc Natl Acad Sci USA 82: 1558–1562, 1985.
Gervasi N, Monnier Z, Vincent P, Paupardin-Tritsch D, Hughes SW, Crunelli V, Leresche N. Pathway-specific action of gamma-hydroxybutyric acid in sensory thalamus and its relevance to absence seizures. J Neurosci 23: 11469–11478, 2003.
Jacobson LH, Kelly PH, Bettler B, Kaupmann K, Cryan JF. GABA(B(1)) receptor isoforms differentially mediate the acquisition and extinction of aversive taste memories. J Neurosci 26: 8800–8803, 2006.
Kulik A, Nakadate K, Nyiri G, Notomi T, Malitschek B, Bettler B, Shigemoto R. Distinct localization of GABA(B) receptors relative to synaptic sites in the rat cerebellum and ventrobasal thalamus. Eur J Neurosci 15: 291–307, 2002.[CrossRef][Web of Science][Medline]
Lee SM, Friedberg MH, Ebner FF. The role of GABA-mediated inhibition in the rat ventral posterior medial thalamus. II. Differential effects of GABAA and GABAB receptor antagonists on responses of VPM neurons. J Neurophysiol 71: 1716–1726, 1994.
LeFeuvre Y, Fricker D, Leresche N. GABAA receptor-mediated IPSCs in rat thalamic sensory nuclei: patterns of discharge and tonic modulation by GABAB autoreceptors. J Physiol 502: 91–104, 1997.
Lüscher C, Jan LY, Stoffel M, Malenka RC, Nicoll RA. G protein-coupled inwardly rectifying K+ channels (GIRKs) mediate postsynaptic but not presynaptic transmitter actions in hippocampal neurons. Neuron 19: 687–695, 1997.[CrossRef][Web of Science][Medline]
Nyitrai G, Emri Z, Crunelli V, Kekesi KA, Dobolyi A, Juhasz G. In vivo blockade of thalamic GABA(B) receptors increases excitatory amino-acid levels. Eur J Pharmacol 318: 295–300, 1996.[CrossRef][Web of Science][Medline]
Ohara PT, Lieberman AR. The thalamic reticular nucleus of the adult rat: experimental anatomical studies. J Neurocytol 14: 365–411, 1985.[CrossRef][Web of Science][Medline]
Perez-Garci E, Gassmann M, Bettler B, Larkum ME. The GABA(B1b) isoform mediates long-lasting inhibition of dendritic Ca(2+) spikes in layer 5 somatosensory pyramidal neurons. Neuron 50: 603–616, 2006.[CrossRef][Web of Science][Medline]
Sakaba T, Neher E. Direct modulation of synaptic vesicle priming by GABA(B) receptor activation at a glutamatergic synapse. Nature 424: 775–778, 2003.[CrossRef][Medline]
Shaban H, Humeau Y, Herry C, Cassasus G, Shigemoto R, Ciocchi S, Barbieri S, van der Putten H, Kaupmann K, Bettler B, Lüthi A. Generalization of amygdala LTP and conditioned fear in the absence of presynaptic inhibition. Nat Neurosci 9: 1028–1035, 2006.[CrossRef][Web of Science][Medline]
Sherman SM, Guillery RW. Functional organization of thalamocortical relays. J Neurophysiol 76: 1367–1395, 1996.
Spreafico R, Battaglia G, Frassoni C. The reticular thalamic nucleus (RTN) of the rat: cytoarchitectural, Golgi, immunocytochemical, and horseradish peroxidase study. J Comp Neurol 304: 478–490, 1991.
Steiger JL, Bandyopadhyay S, Farb DH, Russek SJ. cAMP response element-binding protein, activating transcription factor-4, and upstream stimulatory factor differentially control hippocampal GABABR1a and GABABR1b subunit gene expression through alternative promoters. J Neurosci 24: 6115–6126, 2004.
Stuart GJ, Dodt HU, Sakmann B. Patch-clamp recordings from the soma and dendrites of neurons in brain slices using infrared video microscopy. Pfluegers Arch 423: 511–518, 1993.[CrossRef][Web of Science][Medline]
Turner JP, Salt TE. Group III metabotropic glutamate receptors control corticothalamic synaptic transmission in the rat thalamus in vitro. J Physiol 519: 481–491, 1999.
Ulrich D, Bettler B. GABA-B receptors—synaptic functions and mechanisms of diversity. Curr Opin Neurobiol 17: 298–303, 2007.[CrossRef][Web of Science][Medline]
Ulrich D, Huguenard JR. Purinergic inhibition of GABA and glutamate release in the thalamus: implications for thalamic network activity. Neuron 15: 909–918, 1995.[CrossRef][Web of Science][Medline]
Ulrich D, Huguenard JR. GABAB receptor-mediated responses in GABAergic projection neurones of rat nucleus reticularis thalami in vitro. J Physiol 493: 845–854, 1996.
Vigot R, Barbieri S, Brauner-Osborne H, Turecek R, Shigemoto R, Zhang YP, Lujan R, Jacobson LH, Biermann B, Fritschy JM, Vacher CM, Muller M, Sansig G, Guetg N, Cryan JF, Kaupmann K, Gassmann M, Oertner TG, Bettler B. Differential compartmentalization and distinct functions of GABAB receptor variants. Neuron 50: 589–601, 2006.[CrossRef][Web of Science][Medline]
Wu Y, Chan KF, Eubanks JH, Guin Ting Wong C, Cortez MA, Shen L, Che Liu C, Perez Velazquez J, Tian Wang Y, Jia Z, Snead OC 3rd. Transgenic mice over-expressing GABA(B)R1a receptors acquire an atypical absence epilepsy-like phenotype. Neurobiol Dis 26: 439–451, 2007.[CrossRef][Web of Science][Medline]
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ABSTRACT
INTRODUCTION
