GABAB(1) receptor isoforms differentially mediate the acquisition and extinction of aversive taste memories

Abstract

Conditioned taste aversion (CTA) is a form of aversive memory in which an association is made between a consumed substance and a subsequent malaise. CTA is a critical mechanism for the successful survival, and hence evolution, of most animal species. The role of excitatory neurotransmitters in the neurochemical mechanisms of CTA is well recognized; however, less is known about the involvement of inhibitory receptor systems. In particular, the potential functions of metabotropic GABAB receptors in CTA have not yet been fully explored. GABAB receptors are metabotropic GABA receptors that are comprised of two subunits, GABAB(1) and GABAB(2), which form heterodimers. The Gabbr1 gene is transcribed into two predominant isoforms, GABAB(1a) and GABAB(1b), which differ in sequence primarily by the inclusion of a pair of sushi domains (alsoknownas short consensus repeats) in the GABAB(1a) N terminus. The behavioral function of mammalian GABAB(1) receptor isoforms is currently unknown. Here, using a point mutation strategy in mice, we demonstrate that these two GABAB(1) receptor isoforms are differentially involved in critical components of CTA. In contrast to GABAB(1b)-/- and wild-type mice, GABAB(1a)-/- mice failed to acquire CTA. In contrast, GABAB(1b)-/- mice robustly acquired CTA but failed to show any extinction of this aversion. The data demonstrate that GABAB receptors are involved in both the acquisition and extinction of CTA; however, receptors containing the GABAB(1a) or the GABA B(1b) isoform differentially contribute to the mechanisms used to learn and remember the salience of aversive stimuli. Copyright © 2006 Society for Neuroscience.