Postnatal maturation of GABA_A and GABA_C receptor function in the mammalian superior colliculus

Abstract

In the stratum griseum superficiale (SGS) of the mammalian superior colliculus, GABA(C) receptors seem to control the excitability of projection neurons by selective inactivation of local GABAergic interneurons. As the onset of visual responses to SC begins well after birth in the rat, it is possible to study developmental changes in GABAergic mechanisms that are linked to the onset of visual information processing. In order to analyse postnatal changes in inhibitory mechanisms that involve GABA receptor function, we used extracellular field potential (FP) recordings and single cell patch-clamp techniques in slices from postnatal day 4 (P4) to P32 and examined the effects of GABA and muscimol on electrically evoked SGS cell activity. While GABA(A) receptor activation affected FP amplitudes throughout postnatal development, GABA(C) receptor activation did not significantly change FP amplitudes until the third postnatal week. Results from patch-clamping single cells, however, clearly demonstrate that GABA(C) receptors are already functional at P4--similar to GABA(A) receptors. Throughout postnatal development, activation of GABA(C) receptors leads to a strong inhibition of inhibitory postsynaptic activity, indicating that GABA(C) receptors are expressed by inhibitory interneurons. Furthermore, the proportion of neurons that show decreased excitatory postsynaptic activity during GABA(C) receptor activation correlates with the proportion of GABAergic interneurons in SGS. Our patch-clamp results indicate that the functional expression of GABA(C) receptors by GABAergic interneurons does not change significantly during postnatal development. However, our measurements of FP amplitudes indicate that the maturation of the efferent connections of these GABAergic neurons within SGS during the third postnatal week strongly changes GABA(C) receptor function.

GABAC receptors in the lateral amygdala: a possible novel target for the treatment of fear and anxiety disorders?

“…To elicit postsynaptic currents, electric stimulation was applied to the cortical or thalamic pathway to mimic, in vitro , testing the effects of stimulation of sensory inputs known to occur during fear conditioning in vivo (Romanski et al, 1993; Repa et al, 2001). The effects of the 1 μM muscimol, the GABA agonist, on the electrically evoked responses was assessed since this concentration has been reported to selectively activate GABA C Rs as opposed to GABA A Rs (Pasternack et al, 1999; Boller and Schmidt, 2001; Schmidt et al, 2001). To determine whether this 1 μM muscimol primarily activated GABA C Rs we also examined the effects of blockade of GABA A Rs and GABA B Rs on the electrically evoked responses by adding the GABA A R antagonist bicuculline and the GABA B R antagonist CGP 52432 separately to the bath during recordings.…”

“…Functional GABA C R have been identified in several regions of the nervous system (Johnston et al, 1975; Lukasiewicz et al, 1994; Pan and Lipton, 1995; Delaney and Sah, 1999; Boller and Schmidt, 2001, 2003; Kirischuk et al, 2003; Hartmann et al, 2004), including the lateral part of the central nucleus of the amygdala (CE; Delaney and Sah, 1999), but have not been reported in the LA. Demonstration of the existence of GABA C Rs in the LA and determining their role in amygdala circuitry could lead to a better understanding of inhibitory plasticity in this brain region.…”

Colocalization of synaptic GABAC-receptors with GABAA-receptors and glycine-receptors in the rodent central nervous system

“…Expression of GABA C -receptors in superior colliculus Next to the retina, the evidence for GABA C -receptors is best in the superior colliculus (Boue-Grabot et al 1998;Wegelius et al 1998;Pasternak et al 1999;Boller and Schmidt 2001Schmidt et al 2001. A functional segregation of the two receptor types has been observed.…”

GABAC Receptors in Retina and Brain

“…Results obtained at the single cell level also showed GABA C receptor-specific actions of low GABA concentrations on SGS interneurons (Fig. 4) and thus supported a disinhibitory function of GABA C receptors in the rat SGS Boller and Schmidt 2001).…”