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.
"Consistent with the evidence from the broad spectrum inhibitors, several studies have implicated a role for specific intracellular signaling molecules thought to be “upstream” of protein synthesis in LTM formation and storage (Johansen et al., 2011). For example, inhibition of NMDA receptor (NMDAR) function impairs the consolidation of auditory delay fear and contextual fear memories, fear potentiated startle, and conditioned taste aversion memories in the amygdala (Walker and Davis, 2000; Yasoshima et al., 2000; Rodrigues et al., 2001), auditory trace and contextual fear memories in the prefrontal cortex (Gilmartin and Helmstetter, 2010; Gilmartin et al., 2013a), contextual fear memories, MWM and objection recognition spatial memories in the hippocampus (Liang et al., 1994; Izquierdo et al., 1999; Czerniawski et al., 2012; Da Silva et al., 2013; Warburton et al., 2013), and conditioned taste aversion memories in the insular cortex (Escobar et al., 1998). Inhibition of signaling molecules thought to be downstream of NMDAR activity but upstream of protein synthesis such as Protein Kinase A, ERK-MAPK, and CaMKII impairs memory consolidation for auditory fear memories, contextual fear memories, inhibitory avoidance memories, MWM spatial memories, and conditioned taste aversion memories (Schafe and Ledoux, 2000; Schafe et al., 2000; Sacchetti et al., 2001; Koh et al., 2002; Quevedo et al., 2004; Rodrigues et al., 2004; Leon et al., 2010; Ota et al., 2010; Chen et al., 2012; Halt et al., 2012). "
[Show abstract][Hide abstract] 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.
"One of the IEG is the fos gene family (Milde-Langosch 2005), which is expressed rapidly and transiently in neurons in response to stimuli. C-fos has been shown to play an instrumental role in plasticity, for example, mice lacking the c-fos gene demonstrate impaired hippocampal-dependent learning and memory (Fleischmann et al. 2003) and impaired acquisition and consolidation of aversive taste learning (Yasoshima et al. 2000). Successful efforts have yielded a generation of transgenic mice and rats expressing reporters fused to the c-fos gene, such as β-gal (Kasof et al. 1995; Wilson et al. 2002), green fluorescent protein (GFP) (Barth et al. 2004; Cifani et al. 2012), and monomeric red fluorescent protein-1 (Fujihara et al. 2009). "
[Show abstract][Hide abstract] ABSTRACT: Nerve injury induces long-term changes in neuronal activity in the primary somatosensory cortex (S1), which has often been implicated as the origin of sensory dysfunction. However, the cellular mechanisms underlying this phenomenon remain unclear. C-fos is an immediate early gene, which has been shown to play an instrumental role in plasticity. By developing a new platform to image real-time changes in gene expression in vivo, we investigated whether injury modulates the levels of c-fos in layer V of S1, since previous studies have suggested that these neurons are particularly susceptible to injury. The yellow fluorescent protein, ZsYellow1, under the regulation of the c-fos promoter, was expressed throughout the rat brain. A fiber-based confocal microscope that enabled deep brain imaging was utilized, and local field potentials were collected simultaneously. In the weeks following limb denervation in adult rats (n = 10), sensory stimulation of the intact limb induced significant increases in c-fos gene expression in cells located in S1, both contralateral (affected, 27.6 ± 3 cells) and ipsilateral (8.6 ± 3 cells) to the injury, compared to controls (n = 10, 13.4 ± 3 and 1.0 ± 1, respectively, p value <0.05). Thus, we demonstrated that injury activates cellular mechanisms that are involved in reshaping neuronal connections, and this may translate to neurorehabilitative potential.
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