Post-learning molecular reactivation underlies taste memory consolidation

Abstract

It is considered that memory consolidation is a progressive process that requires post-trial stabilization of the information. In this regard, it has been speculated that waves of receptors activation, expression of immediate early genes, and replenishment of receptor subunit pools occur to induce functional or morphological changes to maintain the information for longer periods. In this paper, we will review data related to neuronal changes in the post-acquisition stage of taste aversion learning that could be involved in further stabilization of the memory trace. In order to achieve such stabilization, evidence suggests that the functional integrity of the insular cortex (IC) and the amygdala (AMY) is required. Particularly the increase of extracellular levels of glutamate and activation of N-methyl-d-aspartate (NMDA) receptors within the IC shows a main role in the consolidation process. Additionally the modulatory actions of the dopaminergic system in the IC appear to be involved in the mechanisms that lead to taste aversion memory consolidation through the activation of pathways related to enhancement of protein synthesis such as the Protein Kinase A pathway. In summary, we suggest that post-acquisition molecular and neuronal changes underlying memory consolidation are dependent on the interactions between the AMY and the IC.

Keywords: conditioned taste aversion; dopamine; glutamate; memory consolidation; molecular reactivation.

Figure 1

(A) Dopamine and (B) glutamate release in the IC during the exposure to novel gustatory stimuli (saccharin 0.1%, quinine 0.005%) or water. Fractions of 4 μL, the first three samples are baseline release before taste stimulation. Data is shown as mean ± SEM;*p < 0.05 and **p < 0.01 vs. same fraction of control group and #p < 0.05 vs. baseline fractions. A significant increase of dopamine is shown in the IC of groups that were exposed to novel taste stimulation.

Figure 2

Short- and long-term memory (STM and LTM) effects of the intra-cortical infusion of SCH23390, a D1 receptors antagonist, into the IC. “SCH23390 before” group and a control group that received saline solution injections (SS before) were injected 15 min prior CTA training (gray triangle) that consisted in the presentation of a saccharine solution (0.1%) during 15 min, followed by an i.p. LiCl administration (0.4 M, 7.5 mL/kg). “SCH 23390 after” and SS after groups received the injections immediately after the saccharin exposure (black triangle). All the groups showed aversion in the STM test (4 h after conditioning), whereas in the LTM test (72 h) only the group that was injected with the D1 antagonist shows an impairment of consolidation. Saccharin consumption during the memory tests are expressed as percentage of consumption during acquisition stage ± SEM. *p < 0.05.

Figure 3

Extracellular dopamine and glutamate levels in the IC increase concomitantly in the post-acquisition period of CTA training. (A) Dopamine monitoring: SAC-LiCl, conditioned group (n = 10) received 0.1% saccharin solution followed by 0.4 M LiCl i.p. injection (7.5 mL/kg); SAC-NaCl, non-conditioned group (n = 7) received 0.1% saccharin solution followed by 0.4 M NaCl i.p. injection (7.5 mL/kg); the CS elicited a dopamine increase in both groups but only the conditioned group showed a post-acquisition increase in the 88-min fraction. (B) Glutamate responses monitoring in conditioned and non-conditioned groups, the US elicited an increment in the SAC-LiCl group due to the LiCl injection but only the conditioned group showed a post-acquisition increase in the 92-min fraction. (C) Dopamine responses of control groups to stimuli: H₂O–LiCl group (n = 5) received tap water followed by 0.4 M LiCl i.p.; H₂O–NaCl group (n = 6) received tap water followed by 0.4 M NaCl i.p.; Dopamine levels are significantly different during saccharin exposure that during water exposure and showed no post-acquisition increments. (D) Glutamate responses to the LiCl and NaCl injection showed no post-acquisition changes, only the one related to the US. (E) Dopamine responses during backward conditioning: LiCl-SAC (n = 7), received 0.4 M LiCl i.p., and later, a 0.1% (wt/vol) saccharin solution; there is no post-acquisition increment. (F) Glutamate response during the backward conditioning. Graphics expressed as means of % baseline release ± SEM. *p < 0.05, and **p < 0.01 vs. control group and #p < 0.05 vs. baseline release (Guzman-Ramos et al., 2010).