Molecular mechanisms underlying memory consolidation of taste information in the cortex

Abstract

The senses of taste and odor are both chemical senses. However, whereas an organism can detect an odor at a relatively long distance from its source, taste serves as the ultimate proximate gatekeeper of food intake: it helps in avoiding poisons and consuming beneficial substances. The automatic reaction to a given taste has been developed during evolution and is well adapted to conditions that may occur with high probability during the lifetime of an organism. However, in addition to this automatic reaction, animals can learn and remember tastes, together with their positive or negative values, with high precision and in light of minimal experience. This ability of mammalians to learn and remember tastes has been studied extensively in rodents through application of reasonably simple and well defined behavioral paradigms. The learning process follows a temporal continuum similar to those of other memories: acquisition, consolidation, retrieval, relearning, and reconsolidation. Moreover, inhibiting protein synthesis in the gustatory cortex (GC) specifically affects the consolidation phase of taste memory, i.e., the transformation of short- to long-term memory, in keeping with the general biochemical definition of memory consolidation. This review aims to present a general background of taste learning, and to focus on recent findings regarding the molecular mechanisms underlying taste-memory consolidation in the GC. Specifically, the roles of neurotransmitters, neuromodulators, immediate early genes, and translation regulation are addressed.

Keywords: ERK; MAPK; conditioned taste aversion; consolidation; gustatory cortex; insular cortex; taste learning; translation regulation.

Figure 1

Neuroanatomy of the taste system. Chemical stimuli originating in alimentary sources, upon reaching the oral cavity initiate the processing of gustatory information (CN, central nucleus; BLA, basolateral amygdala; NST, nucleus of solitary tract; PBN, parabrachial nucleus; pVPMpc, parvocellular part of the ventralis postmedial thalamic nucleus of the thalamus; GC, gustatory cortex). Taste cells, which are broadly tuned to the diverse taste modalities, are innervated by cranial nerves VII, IX, X, which project to the primary gustatory nucleus in the brainstem (NST). The NST sends information to three different systems: the reflex system, the lemniscal system, and the visceral–limbic system. The reflex system comprises medullary and reticular-formation neurons, which innervate the cranial motor nuclei. The lemniscal system consists of projections of the gustatory portion of the NST to the secondary nucleus situated in the dorsal pons (PBN); this, in turn, sends axons to the pVPMpc, which ultimately relays gustatory information to the anterior part of the insular cortex (GC). The visceral–limbic system refers to a collateral network of connections to the hypothalamus and limbic areas in the forebrain, which comprises the central gustatory pathway. The PBN is connected to the amygdala, the hypothalamus, and the bed-nucleus of the stria terminalis. All limbic gustatory targets are interconnected with each other as well as with the PBN and the GC.

Figure 2

The learning process phases: consolidation is determined by type of disruption. The learning process is ethologically divided into consecutive phases of acquisition, consolidation, retrieval, relearning, and reconsolidation. Whereas acquisition, retrieval, and relearning are defined in positive terms, the consolidation and reconsolidation phases are defined in negative terms. Therefore, the duration of the learning process is variable, and dependent on the type of experimental perturbation used to determine consolidation time. The different experimental interferences with consolidation affect different stages of the molecular mechanisms that underlie learning and memory formation. Although the same types of interference may be used to disrupt consolidation and reconsolidation, the time windows of sensitivity to disruption differ between the two phases of learning. It is therefore unclear whether the molecular processes that occur during consolidation are identical to the ones that occur during reconsolidation.

Figure 3

Molecular mechanisms underlying taste learning in the gustatory cortex: schematic simplified representation assuming the different molecular events take place within the same neuron. Glutamate/neuromodulators (Ach, dopamine) reach the postsynaptic site and affect the neuron through specific receptors (NMDAR, AMPAR, mGluR, muscarinic receptors, dopamine receptors, e.g., D1). The receptors are linked to scaffold proteins that form the postsynaptic density (PSD), e.g., MAGUKs, Shank, Homer. MAGUKs are linked through distal scaffolding proteins (DSP) to CamKII. The complexes of receptors and PSD proteins activate signal transduction and hub molecules, which in turn activate transcription and translation regulation. This chain of events, according to our current understanding, results in a new cellular steady state. It is currently unknown whether all molecular processes depicted occur within a single neuron – a question that remains to be further explored. A, neuromodulators/glutamate; B, receptors; C, scaffold proteins; D, signal transduction and hub molecules; E, translation regulation; F, transcription. Key: neuromodulators – white hexagon; glutamate – white ellipse; receptors of neurotransmitters/neuromodulators – blue; representatives of major protein kinases and phosphatases that may have short-term (CamKIIα) or long-term effects-green; protein translation machinery – purple; transcription factors – coral; immediate early genes – red; second messenger – orange. *CaMKII is known to phosphorylate PSD-95 and SAP-97, but it remains to be clarified whether it phosphorylates PSD-93 and SAP-102 as well. In addition, CamKII is well known to activate cytoplasmic polyadenylation element binding protein (CPEB) in other brain regions and in connection with other forms of learning, thereby affecting protein translation. **The BDNF pathway has been simplified; other proteins participate in this pathway.