Disinhibition in Rat Superior Colliculus Mediated by GABA_CReceptors

Abstract

The stratum griseum superficiale (SGS) of the superior colliculus contains a high concentration of the recently described GABA C receptor. In a previous study, it was postulated that activation of these receptors on inhibitory interneurons functions to disinhibit projection cells that relay visual information to the thalamus and brainstem. To test this model, we used in vitro whole-cell patch-clamp methods to measure effects of GABA and muscimol on EPSCs and IPSCs evoked in rat SGS by electrical optic layer stimulation. The neurons were filled with biocytin for later morphological characterization. As expected, bath applications of GABA and muscimol always strongly depressed evoked PSCs at concentrations of Ͼ100 and Ͼ1 M, respectively. However, at lower agonist concentrations, which most likely activate GABA C but not GABA A receptors, effects were not uniform. Evoked responses were suppressed by both agonists in 48% of the neurons, whereas the remaining cells exhibited enhanced responses with increased evoked EPSCs, decreased evoked IPSCs, or both types of change. Most morphologically identified cells with suppressed responses (14 of 17 cells) had morphological characteristics of putative GABAergic interneurons, whereas almost all cells with enhanced responses (8 of 10 cells) had morphological characteristics of projection cells. Finally, all effects of GABA and muscimol at low concentrations were blocked by (1,2,5,6-tetrahydropyridine-4-yl) methylphosphinic acid, a specific GABA C receptor antagonist, but not by the specific GABA A receptor antagonist bicuculline. Taken together, these results indicate that in SGS, GABA C receptors are predominantly expressed by GABAergic neurons and that activation of these receptors leads to disinhibition of SGS projection cells.

Comparison of the ultrastructure of cortical and retinal terminals in the rat superior colliculus

“…However, the superficial layers of the SC contain a wide variety of cell types, including interneurons and cells that project to the parabigeminal nucleus, contralateral SC, pretectum, ventral and dorsal lateral geniculate nuclei, and lateral posterior nucleus (for reviews, see Huerta and Harting, 1984;May, 2006). SC interneurons, tectopretectal, and tectotectal neurons have been found to be GABAergic (Appell and Behan, 1990;Mize, 1992;Schmidt et al, 2001, Baldauf et al, 2003. Thus, these cell types may be ruled out as the primary targets of area 17 terminals.…”

GABAergic mechanisms for shaping transient visual responses in the mouse superior colliculus

“…However, unlike in the retina (McCall et al, 2002), synaptic currents through GABA C receptors were rarely observed in the sSC under normal conditions (Boller and Schmidt, 2003). Additionally, activation of GABA C receptors in the sSC results in disinhibition (Schmidt et al, 2001), suggesting that GABA C receptor blockade might reduce ON activity and augment the pause. Thus, although we did not examine the effect of GABA C receptor blockade, it could be speculated that the contribution of GABA C receptors in the generation and modulation of the ON and pause responses might be minor compared to that of GABA A and GABA B receptors.…”

“…However, because we did not test the effects of juxtasomal current injection on these pharmacologically manipulated neurons, we cannot exclude the possibility that the pause in these neurons might be attributable to a pause of retinal ganglion cells. An alternative candidate might be GABA C receptor-mediated inhibition given that GABA C receptors are reportedly expressed in the sSC (Schmidt et al, 2001;Boller and Schmidt, 2003;Kirischuk et al, 2003). However, unlike in the retina (McCall et al, 2002), synaptic currents through GABA C receptors were rarely observed in the sSC under normal conditions (Boller and Schmidt, 2003).…”

Spatiotemporal Profiles of Field Potentials in Mouse Superior Colliculus Analyzed by Multichannel Recording

“…The circuits that organize this activity have been studied in vitro in slice preparations (for review, see Isa and Saito, 2001;Grantyn et al, 1984;Lee et al, 1997Lee et al, , 2007Isa et al, 1998;Meredith and Ramoa, 1998;Lo and Mize, 2000;Schmidt et al, 2001;Isa, 2002;Isa and Sparks, 2006;Neale and Salt, 2006;Kaneda et al, 2008). Furthermore, profiles of field potential responses at different depths evoked by sSC stimulation were measured by single-electrode recordings in anesthetized rats (Katsuta and Isa, 2003) and monkeys (Nikitin and Isa, 2004).…”