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

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

0028-3908
668-675
Vargas-Caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1
Martin, Loren J.
f12b19fb-d5d6-4d07-9aae-8fbfe1b01eda
Salter, Michael W.
f9c9faa7-d945-4225-8651-7bb4220ece30
Orser, Beverley A.
683cc5b6-932f-48fa-949e-370e5ac1fe27
Paulsen, Ole
fb305f62-2a16-48b0-921a-2cbc59b85c1f
Vargas-Caballero, Mariana
de2178ac-77fd-4748-9fe5-109ab8ad93e1
Martin, Loren J.
f12b19fb-d5d6-4d07-9aae-8fbfe1b01eda
Salter, Michael W.
f9c9faa7-d945-4225-8651-7bb4220ece30
Orser, Beverley A.
683cc5b6-932f-48fa-949e-370e5ac1fe27
Paulsen, Ole
fb305f62-2a16-48b0-921a-2cbc59b85c1f

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)

Record type: Article

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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e-pub ahead of print date: 23 November 2009
Published date: March 2010
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 348177
URI: http://eprints.soton.ac.uk/id/eprint/348177
ISSN: 0028-3908
PURE UUID: 21d80074-1275-4b1d-a222-3d91a234a951
ORCID for Mariana Vargas-Caballero: ORCID iD orcid.org/0000-0003-2326-4001

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Date deposited: 08 Feb 2013 08:51
Last modified: 17 Dec 2019 01:38

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