Behavioral tagging and capture: The impact and the role of neuromodulatory and glutamatergic innervation on hippocampus-dependent memory formation

San Diego, California

Congreso; Neuroscience 2010; 2010

Society for Neuroscience

It is widely accepted that distinct hippocampus-dependent memory consolidation requires the synthesis of plasticity-related proteins (PRPs). These PRPs are generally synthesized by a proper salient experience that will be finally remembered. However, we have recently shown that an inconsequent event unable to be remembered (weak Inhibitory avoidance training: IA) can also use PRPs, provided by another associated event (exploration to a novel open field: OF), in order to stabilize its mnemonic trace for a long period of time. This process, named “behavioral tagging”, depends on the setting of a local learning tag by the inconsequent event IA and also on the synthesis of PRPs induced by the associated event OF, that will later be captured at the tagged sites (Moncada and Viola, 2007).It is also well established that long-term memory (LTM) formation for different learning tasks, including OF and IA, is affected by drugs acting on glutamatergic and catecholaminergic neurotransmitter systems. The infusion of agonists or antagonists into different brain structures can either positively or negatively modulate LTM formation. However, the cellular mechanisms underlying these effects are still unidentified. In other words, the specific role of each of these systems in LTM formation remains unknown. We suggest, that one reason for this is that common studies on memory consolidation have been undertaken using strong salient trainings, which can simultaneously trigger tag setting and PRPs synthesis processes, precluding the identification of the specific role (tag setting or PRPs synthesis) of each of the neurotransmitter systems.Here, we use a combined pharmacological approach with different behavioral tagging-protocols of associative interactions of OF on IA and its impact on LTM formation. Our hypothesis is that IA sets a behavioral tag whereas OF induces PRP-synthesis. Then, specifically interfering with dopaminergic D1/D5, â-adrenergic or glutamatergic NMDA receptor function in dorsal hippocampus before IA or OF training sessions, we could dissect the role of these systems in the one or the other event. We show that neuromodulatory receptors are required to induce the PRP-synthesis necessary for IA-LTM consolidation, while NMDA-receptor activation seems to have a dual function, i.e. it is required for the setting of the IA-learning tag and PRP synthesis. We further show that the tag-setting-machinery also involves the activation of CAMKIIá and PKA but not ERK 1/2. These results support our earlier cellular data obtained in hippocampal brain slices in vitro.