α5 Subunit-containing GABAA receptors mediate a slowly decaying inhibitory synaptic current in CA1 pyramidal neurons following Schaffer collateral activation

NEUROPHARMACOLOGY

卷:58

Article

Vargas-Caballero, Mariana¹  Martin, Loren J.²  Salter, Michael W.^3,4,5  Orser, Beverley A.^2,3,6,7  Paulsen, Ole¹ 

[1] Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England

[2] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada

[3] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada

[4] Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada

[5] Univ Toronto, Univ Toronto Ctr Study Pain, Toronto, ON M5G 1G6, Canada

[6] Univ Toronto, Dept Anesthesia, Toronto, ON M5S 3E2, Canada

[7] Sunnybrook Hlth Sci Ctr, Dept Anesthesia, Toronto, ON M4N 3M5, Canada

关键词: alpha 5;    GABA(A) receptor;    Hippocampus;    Inhibition;    Mouse;    Rat;    Schaffer collateral;   

DOI  :  10.1016/j.neuropharm.2009.11.005

来源: Elsevier

【 摘 要 】

GABA(A) receptors that contain the alpha 5 subunit (alpha 5GABA(A)Rs) 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 alpha 5GABA(A)Rs also contribute to slow phasic inhibition of CA1 pyramidal neurons following local stimulation in the stratum lacunosum moleculare. However, it is unknown whether alpha 5GABA(A)Rs 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 alpha 1/alpha 2/alpha 3 or alpha 5GABA(A)Rs (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 mu M gabazine and were relatively insensitive to L-655,708 consistent with the lack of alpha 5GABA(A)Rs. 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 alpha 5GABA(A)Rs (gabra5(-/-) mice). These results show that alpha 5GABA(A)R-mediated phasic inhibition is activated by the Schaffer collateral pathway and provide evidence for activity pattern-dependent participation of alpha 5GABA(A)Rs in inhibition. (C) 2009 Elsevier Ltd. All rights reserved.

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