| First Author | Heistek TS | Year | 2013 |
| Journal | J Physiol | Volume | 591 |
| Issue | 4 | Pages | 845-58 |
| PubMed ID | 23109109 | Mgi Jnum | J:205980 |
| Mgi Id | MGI:5547492 | Doi | 10.1113/jphysiol.2012.243725 |
| Citation | Heistek TS, et al. (2013) alpha2-containing GABAA receptors expressed in hippocampal region CA3 control fast network oscillations. J Physiol 591(Pt 4):845-58 |
| abstractText | GABA(A) receptors are critically involved in hippocampal oscillations. GABA(A) receptor alpha1 and alpha2 subunits are differentially expressed throughout the hippocampal circuitry and thereby may have distinct contributions to oscillations. It is unknown which GABA(A) receptor alpha subunit controls hippocampal oscillations and where these receptors are expressed. To address these questions we used transgenic mice expressing GABA(A) receptor alpha1 and/or alpha2 subunits with point mutations (H101R) that render these receptors insensitive to allosteric modulation at the benzodiazepine binding site, and tested how increased or decreased function of alpha subunits affects hippocampal oscillations. Positive allosteric modulation by zolpidem prolonged decay kinetics of hippocampal GABAergic synaptic transmission and reduced the frequency of cholinergically induced oscillations. Allosteric modulation of GABAergic receptors in CA3 altered oscillation frequency in CA1, while modulation of GABA receptors in CA1 did not affect oscillations. In mice having a point mutation (H101R) at the GABA(A) receptor alpha2 subunit, zolpidem effects on cholinergically induced oscillations were strongly reduced compared to wild-type animals, while zolpidem modulation was still present in mice with the H101R mutation at the alpha1 subunit. Furthermore, genetic knockout of alpha2 subunits strongly reduced oscillations, whereas knockout of alpha1 subunits had no effect. Allosteric modulation of GABAergic receptors was strongly reduced in unitary connections between fast spiking interneurons and pyramidal neurons in CA3 of alpha2H101R mice, but not of alpha1H101R mice, suggesting that fast spiking interneuron to pyramidal neuron synapses in CA3 contain alpha2 subunits. These findings suggest that alpha2-containing GABA(A) receptors expressed in the CA3 region provide the inhibition that controls hippocampal rhythm during cholinergically induced oscillations. |
