María Cecilia Martínez

Behavioral tagging is a general mechanism of long-term memory formation

In daily life, memories are intertwined events. Little is known about the mechanisms involved in their interactions. Using two hippocampus-dependent (spatial object recognition and contextual fear conditioning) and one hippocampus-independent (conditioned taste aversion) learning tasks, we show that in rats subjected to weak training protocols that induce solely short term memory (STM), long term memory (LTM) is promoted and formed only if training sessions took place in contingence with a novel, but not familiar, experience occurring during a critical time window around training. This process requires newly synthesized proteins induced by novelty and reveals a general mechanism of LTM formation that begins with the setting of a “learning tag” established by a weak training. These findings represent the first comprehensive set of evidences indicating the existence of a behavioral tagging process that in analogy to the synaptic tagging and capture process, need the creation of a transient, protein synthesis-independent, and input specific tag.

Identification of transmitter systems and learning tag molecules involved in behavioral tagging during memory formation.

Long-term memory (LTM) consolidation requires the synthesis of plasticity-related proteins (PRPs). In addition, we have shown recently that LTM formation also requires the setting of a “learning tag” able to capture those PRPs. Weak training, which results only in short-term memory, can set a tag to use PRPs derived from a temporal-spatial closely related event to promote LTM formation. Here, we studied the involvement of glutamatergic, dopaminergic, and noradrenergic inputs on the setting of an inhibitory avoidance (IA) learning tag and the synthesis of PRPs. Rats explored an open field (PRP donor) followed by weak (tag inducer) or strong (tag inducer plus PRP donor) IA training. Throughout pharmacological interventions around open-field and/or IA sessions, we found that hippocampal dopamine D1/D5- and β-adrenergic receptors are specifically required to induce PRP synthesis. Moreover, activation of the glutamatergic NMDA receptors is required for setting the learning tags, and this machinery further required α-Ca2+/calmodulin-dependent protein kinase II and PKA but not ERK1/2 activity. Together, the present findings emphasize an essential role of the induction of PRPs and learning tags for LTM formation. The existence of only the PRP or the tag was insufficient for stabilization of the mnemonic trace.

The tagging and capture hypothesis from synapse to memory.

The synaptic tagging and capture theory (STC) was postulated by Frey and Morris in 1997 and provided a strong framework to explain how to achieve synaptic specificity and persistence of electrophysiological-induced plasticity changes. Ten years later, the same argument was applied on learning and memory models to explain the formation of long-term memories, resulting in the behavioral tagging hypothesis (BT). These hypotheses are able to explain how a weak event that induces transient changes in the brain can establish long-lasting phenomena through a tagging and capture process. In this framework, it was postulated that the weak event sets a tag that captures plasticity-related proteins/products (PRPs) synthesized by an independent strong event. The tagging and capture processes exhibit symmetry, and therefore, PRPs can be captured if they are synthesized either before or after the setting of the tag. In summary, the hypothesis provides a wide framework that gives a solid explanation of how lasting changes occur and how the interaction between different events leads to promotion, reinforcement, or impairment of such changes. In this chapter, we will summarize the postulates of STC hypothesis, the common features between synaptic plasticity and memory, as well as a detailed compilation of the findings supporting the existence of BT process. At the end, we pose some questions related to BT mechanism and LTM formation, which probably will be answered in the near future.

Memory in Elementary School Children Is Improved by an Unrelated Novel Experience

Education is the most traditional means with formative effect on the human mind, learning and memory being its fundamental support. For this reason, it is essential to find different strategies to improve the studentś performance. Based on previous work, we hypothesized that a novel experience could exert an enhancing effect on learning and memory within the school environment. Here we show that novel experience improved the memory of literary or graphical activities when it is close to these learning sessions. We found memory improvements in groups of students who had experienced a novel science lesson 1 hour before or after the reading of a story, but not when these events were 4 hours apart. Such promoting effect on long-term memory (LTM) was also reproduced with another type of novelty (a music lesson) and also after another type of learning task (a visual memory). Interestingly, when the lesson was familiar, it failed to enhance the memory of the other task. Our results show that educationally relevant novel events experienced during normal school hours can improve LTM for tasks/activities learned during regular school lessons. This effect is restricted to a critical time window around learning and is particularly dependent on the novel nature of the associated experience. These findings provide a tool that could be easily transferred to the classroom by the incorporation of educationally novel events in the school schedule as an extrinsic adjuvant of other information acquired some time before or after it. This approach could be a helpful tool for the consolidation of certain types of topics that generally demand a great effort from the children.

Retroactive interference of object-in-context long-term memory: role of dorsal hippocampus and medial prefrontal cortex.

Retroactive interference (RI) is a type of amnesia in which a new learning experience can impair the expression of a previous one. It has been studied in several types of memories for over a century. Here, we aimed to study in the long‐term memory (LTM) formation of an object‐in‐context task, defined as the recognition of a familiar object in a context different to that in which it was previously encountered. We trained rats with two sample trials, each taking place in a different context in association with different objects. Test sessions were performed 24 h later, to evaluate LTM for both object‐context pairs using separate groups of trained rats. Furthermore, given the involvement of hippocampus (Hp) and medial prefrontal cortex (mPFC) in several recognition memories, we also analyzed the participation of these structures in the LTM formation of this task by the local infusion of muscimol. Our results show that object‐in‐context LTM formation is sensitive to RI by a different either familiar or novel object‐context pair trial, experienced 1 h later. This interference occurs in a restricted temporal window and works on the LTM consolidation phase, leaving intact short‐term memory expression. The second sample trial did not affect the object recognition part of the memory. Besides, muscimol treatment before the second sample trial blocks its object‐in‐context LTM and restores the first sample trial memory. We hypothesized that LTM‐RI amnesia is probably caused by resources or cellular machinery competition in these brain regions when they are engaged in memory formation of the traces. In sum, when two different object‐in‐context memory traces are being processed, the second trace interferes with the consolidation of the first one requiring mPFC and CA1 dorsal Hp activation.

The Behavioral Tagging Hypothesis and Its Implications for Long-Term Memory Formation

Memories are experience-dependent internal representations of the world that can last from short periods of time to a whole life. The formation of long-term memories relies on several biochemical changes, which inducing modifications in the synaptic efficiency change the way the neurons communicate each other. Interestingly, the formation of a lasting memory does not entirely depend on learning itself; different events occurring before or after a particular experience can affect its processing, impairing, improving, or even inducing lasting memories. The overlapping of neuronal networks involved in the processing of different types of learning might explain why different experiences interact at neuronal level. However, how and where this does really happen is an issue of study.

Memory consolidation and expression of object recognition are susceptible to retroactive interference.

HighlightsObject recognition long‐term memory is susceptible to retroactive interference.The exposure to a novel object in the same arena exerts an interfering effect.The interference acts on the consolidation and the expression of OR memory.Dorsal hippocampus and medial prefrontal cortex are involved in OR memory. Abstract With the aim of analyzing if object recognition long‐term memory (OR‐LTM) formation is susceptible to retroactive interference (RI), we submitted rats to sequential sample sessions using the same arena but changing the identity of a pair of objects placed in it. Separate groups of animals were tested in the arena in order to evaluate the LTM for these objects. Our results suggest that OR‐LTM formation was retroactively interfered within a critical time window by the exploration of a new, but not familiar, object. This RI acted on the consolidation of the object explored in the first sample session because its OR‐STM measured 3 h after training was not affected, whereas the OR‐LTM measured at 24 h was impaired. This sample session also impaired the expression of OR memory when it took place before the test. Moreover, local inactivation of the dorsal Hippocampus (Hp) or the medial Prefrontal Cortex (mPFC) previous to the exploration of the second pair of objects impaired their consolidation restoring the LTM for the objects explored in the first session. This data suggests that both brain regions are involved in the processing of OR‐memory and also that if those regions are engaged in another process before finishing the first consolidation process its LTM will be impaired by RI.