Abstract
Cell-type specific differences in the kinetics of inhibitory postsynaptic conductance changes (IPSCs) are believed to impact upon network dynamics throughout the brain. Much attention has focused on how GABAA receptor (GABAAR) α and β subunit diversity will influence IPSC kinetics, but less is known about the influence of the γ subunit. We have examined whether GABAAR γ subunit heterogeneity influences IPSC properties in the thalamus. The γ2 subunit gene was deleted from GABAARs selectively in the dorsal lateral geniculate nucleus (dLGN). The removal of the γ2 subunit from the dLGN reduced the overall spontaneous IPSC (sIPSC) frequency across all relay cells and produced an absence of IPSCs in a subset of relay neurons. The remaining slower IPSCs were both insensitive to diazepam and zinc indicating the absence of the γ2 subunit. Because these slower IPSCs were potentiated by methyl-6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), we propose these IPSCs involve γ1 subunit-containing GABAAR activation. Therefore, γ subunit heterogeneity appears to influence the kinetics of GABAAR-mediated synaptic transmission in the visual thalamus in a cell-selective manner. We suggest that activation of γ1 subunit-containing GABAARs give rise to slower IPSCs in general, while faster IPSCs tend to be mediated by γ2 subunit-containing GABAARs.
Highlights
The dorsal lateral geniculate nucleus transmits visual information from the retina to the visual cortex (Nassi and Callaway, 2009) with a variety of modulatory inputs influencing how this information is processed; including glutamatergic cortical inputs, cholinergic brain stem inputs and GABAergic inputs (Sherman and Guillery, 2002; Saalmann and Kastner, 2011)
To test the possibility that other γ subunit-containing GABAA receptor (GABAAR) contribute to the remaining inhibitory postsynaptic conductance changes (IPSCs), we examined the actions of DMCM
What is clear from this study is that the γ2 subunit is associated with fast rising and fast decaying IPSCs, whereas synaptic γ1 subunit-containing GABAARs, contribute to the slow rising and slow decaying spontaneous IPSC (sIPSC) within the dorsal lateral geniculate nucleus (dLGN)
Summary
The dorsal lateral geniculate nucleus (dLGN) transmits visual information from the retina to the visual cortex (Nassi and Callaway, 2009) with a variety of modulatory inputs influencing how this information is processed; including glutamatergic cortical inputs, cholinergic brain stem inputs and GABAergic inputs (Sherman and Guillery, 2002; Saalmann and Kastner, 2011). GABAergic modulation originates from both local interneurons within the dLGN (Rafols and Valverde, 1973; Ohara et al, 1983; Acuna-Goycolea et al, 2008; Seabrook et al, 2013) and external projections from the thalamic reticular nucleus (nRT; Sumitomo et al, 1976; Montero and Scott, 1981) These inputs can shape receptive field properties (Sillito and Kemp, 1983; Norton and Godwin, 1992) and regulate visual attention (Hirsch et al, 2015; Wimmer et al, 2015) through the activation of GABAA and GABAB receptors. The β subunit (β1 to β3) has a more subtle influence on IPSC kinetics related to the phosphorylation status of the β subunit (Nusser et al, 1998; Houston et al, 2009)
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