GABAA Receptors Containing Gamma1 Subunits Contribute to Inhibitory Transmission in the Central Amygdala

Abstract

gamma-Aminobutyric acid (GABA) is the primary inhibitory transmitter in the mammalian brain. This inhibition is mediated by type A (GABA(A)) receptors that are pentameric proteins assembled from 14 different subunits. Although inhibitory synaptic transmission has been studied in the amygdala, the subunit composition of receptors present at different synapses is not well understood. In this study we examined the subunit composition of GABA(A) receptors at synapses in the basolateral and central amygdala. Using receptors expressed in HEK293 cells we first determined the pharmacology of receptors of different subunit compositions. We then used this pharmacological profile to test the properties of receptors present at synapses in the central and basolateral amygdala. These results show that the GABA(A) receptor subunits are differentially distributed in the amygdala. Our data indicate that in the basolateral amygdala, GABAergic synapses are likely composed of receptors that contain alpha2betaxgamma2 subunits. In the central amygdala receptors at the medial input, carrying afferents from the bed nucleus of the stria terminalis contain similar receptors, whereas in the lateral input GABA receptors likely contain gamma1 subunits. These inputs arise from the intercalated cells masses, thought to be responsible for mediating extinction of conditioned fear, raising the possibility of new targets for the treatment of anxiety-related disorders.