Synaptically Released GABA Activates Both Pre- and Postsynaptic GABA_B Receptors in the Rat Globus Pallidus

Abstract

Kaneda, Katsuyuki and Hitoshi Kita. Synaptically released GABA activates both pre-and postsynaptic GABA B receptors in the rat globus pallidus. J Neurophysiol 94: 1104 -1114, 2005; doi:10.1152/jn.00255.2005. The globus pallidus (GP) contains abundant GABAergic synapses and GABA B receptors. To investigate whether synaptically released GABA can activate pre-and postsynaptic GABA B receptors in the GP, physiological recordings were performed using rat brain slice preparations. Cell-attached recordings from GABA A antagonist-treated preparations revealed that repetitive local stimulation induced a GABA B antagonist-sensitive pause in spontaneous firings of GP neurons. Whole cell recordings revealed that the repetitive stimulation evoked fast excitatory postsynaptic potentials followed by a slow inhibitory postsynaptic potential (IPSP) in GP neurons. The slow IPSP was insensitive to a GABA A receptor antagonist, increased in amplitude with the application of ionotropic glutamate receptor antagonists, and was suppressed by the GABA B antagonist CGP55845. The reversal potential of the slow IPSP was close to the potassium equilibrium potential. These results suggest that synaptically released GABA activated postsynaptic GABA B receptors and induced the pause and the slow IPSP. On the other hand, in the neurons that were treated to block postsynaptic GABA B responses, CGP55845 increased the amplitudes of repetitive local stimulationinduced GABA A -mediated inhibitory postsynaptic currents (IPSCs) but not the ionotropic glutamate-mediated excitatory postsynaptic currents. Moreover, the GABA B receptor specific agonist baclofen reduced the frequency of miniature IPSCs without altering their amplitude distributions. These results suggest that synaptically released GABA also activated presynaptic GABA B autoreceptors, resulting in decreased GABA release in the GP. Together, we infer that both pre-and postsynaptic GABA B receptors may play crucial roles in the control of GP neuronal activity.

Tonic Activation of GABAB Receptors Reduces Release Probability at Inhibitory Connections in the Cerebellar Glomerulus

“…The effects of the GABA B receptor antagonist CGP55845 were similar to those caused by increasing extracellular Ca 2ϩ , consistent with the observation that CGP55845 preferentially inhibits presynaptic GABA B receptors (Yamada et al 1999; see also Chen and Yung 2005;Fearon et al 2003;Jensen et al 1999;Kaneda and Kita 2005;Than and Szabo 2002). Moreover, the action of CGP55845, by occurring in the first response in a train, reveals the blockage of GABA B receptors that were tonically activated.…”

“…The inset shows exponential fitting to the decay of an IPSC in the train, which was needed to determine the baseline from which the amplitude of the subsequent IPSC could be measured. B: plot of normalized eIPSC peak amplitude (mean Ϯ MSE) in the train for 8 experiments, like those shown in A (0.5 mM [Ca 2ϩ ] o , n ϭ 5; 2 mM [Ca 2ϩ ] o , n ϭ 8 high-affinity GABA B receptor blocker CGP55845, which is reported to act preferentially on presynaptic GABA B receptors (Chen and Yung 2005;Fearon et al 2003;Jensen et al 1999;Kaneda and Kita 2005;Than and Szabo 2002;Yamada et al 1999). Another GABA B receptor antagonist, CGP35348 (Deisz et al 1997;Morishita and Sastry 1995;Mouginot et al 1998), was not used since it is known to block postsynaptic GABA B receptors at the Golgi cell-granule cell synapses and could generate spurious effects on eIPSCs .…”

“…GABA B receptors, in turn, can limit GABA release (Chen and Yung 2005;Deisz et al 1997;Fearon et al 2003;Jensen et al 1999;Kaneda and Kita 2005;Morishita and Sastry 1995;Mouginot et al 1998;Than and Szabo 2002) through a presynaptic mechanism. It has been proposed that, at central synapses, this mechanism could operate by reducing presynaptic calcium influx and synaptic vesicle recovery (Dittman and Regehr 1996;Sakaba and Neher 2003;Takahashi et al 1998), thereby regulating the dynamics of repetitive neurotransmission (Hefft et al 2002).…”

Regulation of Burst Activity through Presynaptic and Postsynaptic GABABReceptors in Mouse Superior Colliculus

“…This is in accordance with previous findings that GABA B Rs are localized in perisynaptic (Kulik et al, 2002) and extrasynaptic (Kulik et al, 2003) sites, although it remains unclear whether this is also true of the SC, and that affinity of GABA for GABA B Rs is lower than that for GABA A Rs (Curtis et al, 1970;Chu et al, 1990). We also found that repetitive stimulation was required to activate GABA B Rs in the SC, as has been observed in various brain regions (Johnson et al, 1992;Isaacson et al, 1993;Mitchell and Silver, 2000;Saitoh et al, 2004;Kaneda and Kita, 2005).…”

Nigral Inhibition of GABAergic Neurons in Mouse Superior Colliculus

“…The bath contained CNQX and APV. The stimulating electrodes were placed just ventral to the SC, and repetitive stimulation (20 -50 pulses at 50 Hz) was delivered to elicit the large amount of GABA release that should be necessary for activating GABA B receptors (Isaacson et al, 1993;Mitchell and Silver, 2000;Kaneda and Kita, 2005;Kaneda et al, 2008). Although this stimulation would activate both nigral and other passing GABAergic fibers, including those from the zona incerta and reticular formation (Ficalora and Mize, 1989;Appell and Behan, 1990;Kim et al, 1992;May et al, 1997;Kolmac et al, 1998), the stimulation-evoked IPSCs were not affected by bath application of the selective GABA B receptor antagonist CGP52432 (3 M) in six of six neurons tested (Fig.…”