GABAB autoreceptors mediate activity-dependent disinhibition and enhance signal transmission in the dentate gyrus

Abstract

1. Activity-dependent depression (fading) of polysynaptic inhibition and the effects of this disinhibition on signal transmission were studied in the dentate gyrus of the rat hippocampal slice with the use of intracellular and extracellular recordings. 2. Polysynaptic inhibitory postsynaptic potentials/currents (IPSP/Cs) were evoked in dentate granule cells by stimulation of mossy fibers in stratum lucidum of area CA3b/c. These mossy fiber-evoked IPSP/Cs consisted of an early GABAA receptor-mediated component (IPSP/CA) and a late GABAB receptor-mediated component (IPSP/CB). 3. When paired stimuli were delivered 200 ms apart under voltage clamp, the amplitude of the IPSCA and IPSCB evoked by the second stimulus was reduced by 37.0 +/- 4.0 and 61.6 +/- 7.8% (mean +/- SE), respectively. Paired-pulse depression of both IPSCA and IPSCB was greatest at interstimulus intervals of 100-400 ms with a maximal effect when stimuli were delivered 200 ms apart. 4. (+/-) Baclofen, a GABAB receptor agonist, suppressed both components of the mossy fiber-evoked IPSP in a concentration-dependent fashion. At a concentration that only partially suppressed the initial IPSP, baclofen occluded paired-pulse depression of IPSPA. In addition, paired-pulse depression of IPSPA was blocked in a concentration-dependent fashion by 2-hydroxy-saclofen (10-400 microM), a GABAB receptor antagonist. 5. The contribution of the IPSPB conductance increase to paired-pulse depression of IPSPA was evaluated. Paired-pulse depression of IPSPA was significantly greater than was the depression of the response to a current pulse delivered 200 ms after the mossy fiber stimulus. In addition, injection of granule cells with GTP gamma S, a nonhydrolyzable guanosine triphosphate (GTP) analogue, occluded both IPSPB as well as the effects of baclofen on the granule cell membrane by activating G proteins but did not reduce paired-pulse depression of IPSPA or suppression of IPSPA by baclofen. Finally, examination of the first and second IPSCA evoked by paired stimuli 200 ms apart revealed no significant differences in response kinetics. Taken together, these results indicate that postsynaptic GABAB receptors on the granule cells are not responsible for paired-pulse depression of IPSPA. 6. Monosynaptic IPSPs were evoked by direct stimulation of inhibitory neurons in the inner molecular layer of the dentate gyrus during pharmacological blockade of excitatory transmission with D(-)-2-amino-5-phosphonovaleric acid (D-APV), an N-methyl-D-aspartate (NMDA) receptor antagonist and 6,7-dinitroquinoxaline-2,3-dione (DNQX), a non-NMDA glutamate receptor antagonist.(ABSTRACT TRUNCATED AT 400 WORDS)

LTP in hippocampal area CA1 is induced by burst stimulation over a broad frequency range centered around delta

“…GABA B autoreceptors maximally suppress GABA release when priming stimulation precedes a stimulus burst by 150-200 msec (Davies et al 1990;Davies and Collingridge 1993;Mott et al 1993), and suppression of inhibition during the primed burst is critical for activation of NMDA receptors (Morrisett et al 1991;Davies and Collingridge 1996) and LTP induction Pacelli et al 1989). Because GABA B autoreceptor-mediated inhibition of GABA release is less effective when stimulation intervals exceed 200 msec, and because we observed strong suppression of inhibition even at 1-sec intervals between bursts, we suggest that an additional process must underlie the progressive loss of inhibition during repeated burst stimulation at intervals $500 msec.…”

“…Activation of GABA B autoreceptors during the priming stimulus suppresses GABA release during the following burst (Davies et al 1990;Lambert and Wilson 1994;Olpe et al 1994), allowing greater postsynaptic depolarization Pacelli et al 1989) and more effective NMDA receptor activation (Davies and Collingridge 1996). Consequently, temporal requirements for primed burst potentiation match the time course of GABA B autoreceptor-mediated suppression of GABA release (Davies et al 1990;Davies and Collingridge 1993;Mott et al 1993).Besides theta, hippocampal activity is observed at other frequencies, notably sharp waves (0.01-5 Hz) (Buzsáki 1986(Buzsáki , 1989Suzuki and Smith 1987) and low-frequency oscillations (#1 Hz) (Wolansky et al 2006;Moroni et al 2007). These lower frequencies dominate during slow wave sleep (Buzsáki 1986;Suzuki and Smith 1987;Wolansky et al 2006;Moroni et al 2007), and contribute to hippocampal memory processing (Buzsáki 1989;Pennartz et al 2002).…”

“…Activation of GABA B autoreceptors during the priming stimulus suppresses GABA release during the following burst (Davies et al 1990;Lambert and Wilson 1994;Olpe et al 1994), allowing greater postsynaptic depolarization Pacelli et al 1989) and more effective NMDA receptor activation (Davies and Collingridge 1996). Consequently, temporal requirements for primed burst potentiation match the time course of GABA B autoreceptor-mediated suppression of GABA release (Davies et al 1990;Davies and Collingridge 1993;Mott et al 1993).…”

Short-Term Plasticity during Intrathalamic Augmenting Responses in Decorticated Cats

“…7, 10). Disinhibition also causes enhanced signal transmission in the dentate gyrus when stimuli are delivered between 2.5 and 10 Hz (Mott et al, 1993). In the auditory cortex too, the enhancement of late EPSPs produced by paired-pulse (200 msec intervals) stimulation was a result of release from GABAergic IPSPs (Metherate and Ashe, 1994).…”

, Frequency-Dependent Modulation of Short-Term Plasticity of Gabaergic Synaptic Transmission

“…Відомо, що зміна частоти та тривалості попередньої активності пресинаптичних нейронів здатна моделювати ефективність синаптичної пе-редачі між ними. Це питання є важливим і досить дослідженним in vitro на зрізах та в культурі клітин ЦНС [11,12]. Вплив частот-ної модуляції на короткотривалу депресію та полегшення синаптичної передачі між нейро-нами гіпокампа краще описана для збудливих синапсів [14,13] і менше для гальмівних.…”