| First Author | Sun MY | Year | 2018 |
| Journal | J Neurosci | Volume | 38 |
| Issue | 38 | Pages | 8128-8145 |
| PubMed ID | 30076210 | Mgi Jnum | J:265920 |
| Mgi Id | MGI:6200183 | Doi | 10.1523/JNEUROSCI.0799-18.2018 |
| Citation | Sun MY, et al. (2018) Chemogenetic Isolation Reveals Synaptic Contribution of delta GABAA Receptors in Mouse Dentate Granule Neurons. J Neurosci 38(38):8128-8145 |
| abstractText | Two major GABAA receptor classes mediate ionotropic GABA signaling, those containing a delta subunit and those with a gamma2 subunit. The classical viewpoint equates gamma2-containing receptors with IPSCs and delta-containing receptors with tonic inhibition because of differences in receptor localization, but significant questions remain because the populations cannot be pharmacologically separated. We removed this barrier using gene editing to confer a point mutation on the delta subunit in mice, rendering receptors containing the subunit picrotoxin resistant. By pharmacologically isolating delta-containing receptors, our results demonstrate their contribution to IPSCs in dentate granule neurons and weaker contributions to thalamocortical IPSCs. Despite documented extrasynaptic localization, we found that receptor localization does not preclude participation in isolated IPSCs, including mIPSCs. Further, phasic inhibition from delta subunit-containing receptors strongly inhibited summation of EPSPs, whereas tonic activity had little impact. In addition to any role that delta-containing receptors may play in canonical tonic inhibition, our results highlight a previously underestimated contribution of delta-containing receptors to phasic inhibition.SIGNIFICANCE STATEMENT GABAA receptors play key roles in transient and tonic inhibition. The prevailing view suggests that synaptic gamma2-containing GABAA receptors drive phasic inhibition, whereas extrasynaptic delta-containing receptors mediate tonic inhibition. To re-evaluate the impact of delta receptors, we took a chemogenetic approach that offers a sensitive method to probe the synaptic contribution of delta-containing receptors. Our results reveal that localization does not strongly limit the contribution of delta receptors to IPSCs and that delta receptors make an unanticipated robust contribution to phasic inhibition. |
