GABA_B receptor modulation of excitatory and inhibitory synaptic transmission onto rat CA3 hippocampal interneurons

Abstract

Journal of Physiologyrelease at either excitatory or inhibitory synapses onto CA3 interneurons has not been elucidated.In the present paper, we examine the effects of GABA B receptor activation on excitatory and inhibitory synaptic transmission onto interneurons located in the CA3 st. radiatum. Our results indicate that activation of GABA B receptors inhibits both excitatory and inhibitory synaptic transmission at CA3 interneuron synapses via presynaptic mechanisms. METHODS Hippocampal slice preparationTransverse hippocampal slices (300 mm) were obtained from 16-18-day-old Sprague-Dawley rats, unless otherwise stated in the text, as described previously (Toth & McBain, 1998;Lei & McBain, 2002). Rats were deeply anaesthetized with isoflurane, rapidly decapitated, and the brain dissected out in ice-cold saline solution that contained (mM): 130 NaCl, 24 NaHCO 3 , 3.5 KCl, 1.25 NaH 2 PO 4 , 1.0 CaCl 2 , 5.0 MgCl 2 , and 10 glucose, saturated with 95 % O 2 and 5 % CO 2 , pH 7.4. All animal procedures conformed to the National Institutes of Health animal welfare guidelines. ElectrophysiologyWhole-cell patch-clamp recordings were made from visually identified interneurons located in the st. radiatum of CA3 by the use of an Axopatch 1D amplifier (Axon Instruments, Foster City, CA, USA) in voltage-clamp mode. Unless otherwise stated, recording electrodes were filled with the following (mM): 100 caesium gluconate, 0.6 EGTA, 5 MgCl 2 , 8 NaCl, 2 ATP 2 Na, 0.3 GTPNa, 40 Hepes, and 1 QX-314, pH 7.2-7.3. Biocytin (0.2 %) was routinely added to the recording electrode solution to allow post hoc morphological processing of recorded cells (Toth & McBain, 1998). In experiments where postsynaptic GABA B responses were investigated, caesium gluconate was replaced by equimolar potassium gluconate in the internal solution. The extracellular solution comprised the following (mM): 130 NaCl, 24 NaHCO 3 , 3.5 KCl, 1.25 NaHPO 4 , 1.5 MgCl 2 , 2.5 CaCl 2 and 10 glucose, saturated with 95 % O 2 and 5 % CO 2 , pH 7.4.

The GABAB1aIsoform Mediates Heterosynaptic Depression at Hippocampal Mossy Fiber Synapses

“…This agrees with ultrastructural data demonstrating that most GABA B receptors are located distant from release sites (Ló pez-Bendito et al, 2004;Lacey et al, 2005;Kulik et al, 2006). A tonic activation of GABA B receptors through ambient GABA was also observed, which may partly explain their predominantly extrasynaptic lo-calization as well (Lei and McBain, 2003;Price et al, 2005;Liu et al, 2006). GABA B receptors are heteromers composed of GABA B1 and GABA B2 subunits (Calver et al, 2002;Bettler et al, 2004).…”

Presynaptic GABAB Receptors Modulate Thalamic Excitation of Inhibitory and Excitatory Neurons in the Mouse Barrel Cortex

“…7D). These results are consistent with the EC 50 of baclofen-mediated inhibition of hippocampal EPSCs (Lei and McBain 2003;Wu and Saggau 1995). Therefore the apparent discrepancy between our results and the previous study can be accounted for by the difference in the concentrations of baclofen.…”

“…2003; Gaiarsa et al 1995;Isaacson 1998;Kombian et al 1996;Lei and McBain 2003;Morishita and Sastry 1995;Nisenbaum et al 1992;Wu and Saggau 1995;Yamada et al 1999), including intracortical glutamatergic synapses in the cerebral cortex (Chu and Hablitz 2003;Fukuda et al 1993;Gil et al 1997;Zilberter et al 1999).…”

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

“…In the hippocampus, GABA B receptor-mediated postsynaptic, but not presynaptic, responses are developmentally regulated (Lei and McBain, 2003). Moreover, responses mediated by postsynaptic GABA B receptors desensitize more rapidly than those mediated by presynaptic receptors (Wetherington and Lambert, 2002).…”