Different disruptive effects on the acquisition and expression of conditioned taste aversion by blockades of amygdalar ionotropic and metabotropic glutamatergic receptor subtypes in rats
ABSTRACT Conditioned taste aversion (CTA) is based on the gustatory long-term memory established after association of the taste of food (conditioned stimulus, CS) with visceral signals of poisoning (unconditioned stimulus, US). After the acquisition of CTA, hedonics of the taste CS changes from positive to negative as indicated by reduced ingestive and increased aversive taste reactivities in response to re-exposures to the CS. We examined the effects of reversible and selective blockades of the amygdalar glutamate receptor subtypes, AMPA, NMDA and metabotropic glutamate receptors, on the formation of CTA. Blockades of each of the three receptor subtypes between ingestion of saccharin (CS) and malaise-inducing LiCl (US) disrupted the acquisition of CTA. After the acquisition of CTA, however, blockades of only AMPA receptors, but not NMDA or metabotropic receptors, impaired the expression of CTA. This effect was seen only during the period when the antagonistic action to AMPA receptors lasted. These results indicate that both ionotropic and metabotropic glutamate receptor subtypes in the amygdala are indispensable for the acquisition of CTA, but that the expression of acquired CTA is mediated only by AMPA receptors. The present results also suggest that the amygdalar glutamatergic neural transmission is involved in the formation and storage of long-term gustatory memory associated with the altered hedonics from positive to negative.
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ABSTRACT: Long-term memory (LTM) formation requires transient changes in the activity of intracellular signaling cascades that are thought to regulate new gene transcription and de novo protein synthesis in the brain. Consistent with this, protein synthesis inhibitors impair LTM for a variety of behavioral tasks when infused into the brain around the time of training or following memory retrieval, suggesting that protein synthesis is a critical step in LTM storage in the brain. However, evidence suggests that protein degradation mediated by the ubiquitin-proteasome system may also be a critical regulator of LTM formation and stability following retrieval. This requirement for increased protein degradation has been shown in the same brain regions in which protein synthesis is required for LTM storage. Additionally, increases in the phosphorylation of proteins involved in translational control parallel increases in protein polyubiquitination and the increased demand for protein degradation is regulated by intracellular signaling molecules thought to regulate protein synthesis during LTM formation. In some cases inhibiting proteasome activity can rescue memory impairments that result from pharmacological blockade of protein synthesis, suggesting that protein degradation may control the requirement for protein synthesis during the memory storage process. Results such as these suggest that protein degradation and synthesis are both critical for LTM formation and may interact to properly “consolidate” and store memories in the brain. Here, we review the evidence implicating protein synthesis and degradation in LTM storage and highlight the areas of overlap between these two opposing processes. We also discuss evidence suggesting these two processes may interact to properly form and store memories. LTM storage likely requires a coordinated regulation between protein degradation and synthesis at multiple sites in the mammalian brain.Frontiers in Molecular Neuroscience 06/2014; 7(61). DOI:10.3389/fnmol.2014.00061
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ABSTRACT: Cortical glutamatergic activity is known to be important for memory formation in different learning tasks. For example, glutamate activity in the insular cortex plays an important role in aversive taste memory formation by signaling the unconditioned stimulus. However, the role of glutamate in the insular cortex in appetitive taste learning has remained poorly studied. Therefore, we considered the function of glutamate in attenuation of neophobia, a model of appetitive taste recognition memory. For this purpose, we performed infusions of vehicle, glutamate, a specific mGluR1 antagonist (AIDA) or a combination of glutamate and AIDA at 0 or 30minutes, and glutamate or vehicle at 60minutes after novel saccharin consumption. Glutamate infusion impaired appetitive taste recognition memory when infused at 0 or 30minutes, whereas, AIDA infusions produced enhanced appetitive memory at the same infusion times. Furthermore, when glutamate and AIDA were infused together no effect on attenuation of neophobia was observed. As opposed to shorter infusion times, the administration of glutamate 60minutes after the presentation of the saccharin consumption was ineffective in the impairment of the appetitive taste memory. These results are discussed in view of the effect of glutamate and its mGluR1 during the appetitive taste recognition memory formation in the insular cortex. Copyright © 2015. Published by Elsevier B.V.Behavioural Brain Research 02/2015; 284. DOI:10.1016/j.bbr.2015.02.020 · 3.39 Impact Factor
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ABSTRACT: Conditioned taste aversion (CTA) can be applied to study associative learning and its relevant underpinning molecular mechanisms in discrete brain regions. The present study examined, by immunohistochemistry and immunocytochemistry, the effects of acquisition and expression of lithium-induced CTA on activated Extracellular signal Regulated Kinase (p-ERK) in the prefrontal cortex (PFCx) and nucleus accumbens (Acb) of male Sprague-Dawley rats. The study also examined, by immunoblotting, whether acquisition and expression of lithium-induced CTA resulted in modified levels of phosphorylation of glutamate receptor subunits (NR1 and GluR1) and Thr(34)- and Thr(75-Dopamine-and-cAMP-Regulated) PhosphoProtein (DARPP-32). CTA acquisition was associated with an increase of p-ERK-positive neurons and phosphorylated NR1 receptor subunit (p-NR1) in the PFCx, whereas p-GluR1, p-Thr(34)- and p-Thr(75)-DARPP-32 levels were not changed in this brain region. CTA expression increased the number of p-ERK-positive neurons in the shell (AcbSh) and core (AcbC) but left unmodified p-NR1, p-GluR1, p-Thr(34)- and p-Thr(75-DARPP-32) levels. Furthermore, post-embedding immunogold quantitative analysis in AcbSh revealed that CTA expression significantly increased nuclear p-ERK immunostaining as well as p-ERK-labeled axo-spinous contacts. Overall, these results indicate that ERK and NR1, but not GluR1 and DARPP-32, are differentially phosphorylated as a consequence of acquisition and expression of aversive associative learning. Moreover, these results confirm that CTA represents an useful approach to study the molecular basis of associative learning in rats and suggest the involvement of ERK cascade in learning-associated synaptic plasticity.Frontiers in Behavioral Neuroscience 05/2014; 8:153. DOI:10.3389/fnbeh.2014.00153 · 4.16 Impact Factor