Biochemical modulation of NMDA receptors: role in conditioned taste aversion

Abstract

Glutamate neurotransmission plays a crucial role in a variety of functions in the central nervous system, including learning and memory. However, little is known about the mechanisms underlying this process in mammals because of the scarceness of experimental models that permit correlation of behavioral and biochemical changes occurring during the different stages of learning and the retrieval of the acquired information. One model that has been useful to study these mechanisms is conditioned taste aversion (CTA), a paradigm in which animals learn to avoid new tastes when they are associated with gastrointestinal malaise. Glutamate receptors of the N-methyl-D-aspartate (NMDA) type appear to be necessary in this process, because blockade of this receptor prevents CTA. Phosphorylation of the main subunits of the NMDA receptor is a well-established biochemical mechanism for the modulation of the receptor response. Such modulation seems to be involved in CTA, because inhibitors of protein kinase C (PKC) block CTA acquisition and because the exposure to an unfamiliar taste results in an increased phosphorylation of tyrosine and serine residues of the NR2B subunit of the receptor in the insular cortex, the cerebral region where gustatory and visceral information converge. In this work we review these mechanisms of NMDA receptor modulation in CTA.