| First Author | Herd MB | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 37 | Pages | 14850-68 |
| PubMed ID | 24027285 | Mgi Jnum | J:202334 |
| Mgi Id | MGI:5518498 | Doi | 10.1523/JNEUROSCI.1174-13.2013 |
| Citation | Herd MB, et al. (2013) Extrasynaptic GABA(A) receptors couple presynaptic activity to postsynaptic inhibition in the somatosensory thalamus. J Neurosci 33(37):14850-68 |
| abstractText | Thalamocortical circuits govern cognitive, sensorimotor, and sleep-related network processes, and generate pathological activities during absence epilepsy. Inhibitory control of thalamocortical (TC) relay neurons is partially mediated by GABA released from neurons of the thalamic reticular nucleus (nRT), acting predominantly via synaptic alpha1beta2gamma2 GABA(A) receptors (GABA(A)Rs). Importantly, TC neurons also express extrasynaptic alpha4beta2delta GABA(A)Rs, although how they cooperate with synaptic GABA(A)Rs to influence relay cell inhibition, particularly during physiologically relevant nRT output, is unknown. To address this question, we performed paired whole-cell recordings from synaptically coupled nRT and TC neurons of the ventrobasal (VB) complex in brain slices derived from wild-type and extrasynaptic GABA(A)R-lacking, alpha4 "knock-out" (alpha4(0/0)) mice. We demonstrate that the duration of VB phasic inhibition generated in response to nRT burst firing is greatly reduced in alpha4(0/0) pairs, suggesting that action potential-dependent phasic inhibition is prolonged by recruitment of extrasynaptic GABA(A)Rs. Furthermore, the influence of nRT tonic firing frequency on VB holding current is also greatly reduced in alpha4(0/0) pairs, implying that the alpha4-GABA(A)R-mediated tonic conductance of relay neurons is dynamically influenced, in an activity-dependent manner, by nRT tonic firing intensity. Collectively, our data reveal that extrasynaptic GABA(A)Rs of the somatosensory thalamus do not merely provide static tonic inhibition but can also be dynamically engaged to couple presynaptic activity to postsynaptic excitability. Moreover, these processes are highly sensitive to the delta-selective allosteric modulator, DS2 and manipulation of GABA transport systems, revealing novel opportunities for therapeutic intervention in thalamocortical network disorders. |
