?5 Subunit-containing GABAA receptors mediate a slowly decaying inhibitory synaptic current in CA1 pyramidal neurons following Schaffer collateral activation

Vargas-Caballero, Mariana, Martin, Loren J., Salter, Michael W., Orser, Beverley A. and Paulsen, Ole (2010) ?5 Subunit-containing GABAA receptors mediate a slowly decaying inhibitory synaptic current in CA1 pyramidal neurons following Schaffer collateral activation. Neuropharmacology, 58 (3), 668-675. (doi:10.1016/j.neuropharm.2009.11.005). (PMID:19941877)

Abstract

GABAA receptors that contain the ?5 subunit (?5GABAARs) are highly expressed in the hippocampus, and have been implicated in learning and memory processes. They generate a tonic form of inhibition that regulates neuronal excitability. Recently it was shown that ?5GABAARs also contribute to slow phasic inhibition of CA1 pyramidal neurons following local stimulation in the stratum lacunosum moleculare. However, it is unknown whether ?5GABAARs can also be recruited indirectly by stimulation of Schaffer collaterals. Here, we studied GABAergic currents evoked by stimulation in the stratum radiatum of CA1 in the presence and absence of CNQX to block AMPA receptor-mediated excitation. We tested their sensitivity to gabazine and two drugs acting at the benzodiazepine site of ?1/?2/?3 or ?5GABAARs (400 nM zolpidem and 20 nM L-655,708, respectively). IPSCs evoked by stimulation in the stratum radiatum in the presence of CNQX were potentiated by zolpidem, blocked by 1 ?M gabazine and were relatively insensitive to L-655,708 consistent with the lack of ?5GABAARs. In contrast, IPSCs evoked by stimulation of Schaffer collaterals had a significant gabazine-insensitive component. This component was attenuated by L-655,708 and enhanced by burst stimulation. Furthermore, the L-655,708-sensitive current was absent in recordings from mice lacking ?5GABAARs (gabra5?/? mice). These results show that ?5GABAAR-mediated phasic inhibition is activated by the Schaffer collateral pathway and provide evidence for activity pattern-dependent participation of ?5GABAARs in inhibition

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Contributors

Author: Mariana Vargas-Caballero

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