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

Abstract

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.hippocampus ͉ insular cortex ͉ memory consolidation ͉ protein synthesis ͉ novelty A cquisition of new information can be stored into at least two temporally and mechanistically different memory types: a short-term (STM) and a long-term memory (LTM). It is well known that in order for LTM to be established, synaptic changes must be stabilized by the action of newly synthesized proteins (1). This process of memory trace consolidation takes place in the brain areas where such forms of learning and memory are likely to reside. Surprisingly, recent evidence demonstrated that the supply of newly synthesized proteins may also derived from another behavioral event occurring in a relatively long-lasting associative time window, helping to promote LTM for a weak learning task that otherwise would only induce STM (2).Current models, based on seminal ideas, propose that memories are stored by stable changes in synaptic weight modifying the activity of specific neuronal circuits (3-5). Therefore, those specific synapses activated by a given learning will require the supply of new plasticity-related proteins (PRPs) for LTM to be formed. As a consequence, there should be a mechanism that restricts the action of PRPs to recently activated synapses but not to others. To address this biological problem, it was suggested that a transient local synaptic tag is established at those recently activated synapses where PRPs are specifically captured. This idea was originally postulated by Frey and Morris (6) and it is now known as the synaptic tagging and capture (STC) hypothesis (7-9). In their seminal work they showed that early-LTP, a transient form of LTP that is induced by a weak stimulus, could be extended to late-LTP, a more persistent form of LTP, if the weak and the strong stimuli were applied in a relatively long-lasting associative time window on different synapses of the same neuron. Frey and colleagues also found that an hippocampal LTP can be reinforced by exposing rats to a novelty ...

Asymmetrical Synaptic Cooperation between Cortical and Thalamic Inputs to the Amygdale

“…Recently, several studies have shown that memories can interact with each other by means of synaptic tagging and capture (Almaguer-Melian et al, 2012;Ballarini et al, 2009;Moncada and Viola, 2007;Wang et al, 2010;Myskiw et al, 2013). All these studies show that exposure to novelty can upregulate the synthesis of PRPs, presumably through the release of dopamine, which are then captured at tagged synapses in a cooperative fashion.…”

Influence of reward motivation on human declarative memory

“…Importantly, the memory-stabilizing effect of dopamine extends to other information encoded when dopamine is available, a phenomenon also referred to as the 'penumbra hypothesis' (Lisman et al, 2011). The hypothesis predicts that once dopamine availability is enhanced, any encoded information will benefit from preferential consolidation, regardless of the actual trigger of the dopamine release (Lisman et al, 2011), and initial evidence from rodent (Ballarini et al, 2009; and human (Fenker et al, 2008;Wittmann et al, 2011) data points out that it may indeed be so. Boosts in dopamine availability at encoding thus result in memory being more stable and better protected from forgetting, an effect that may predominantly arise at long (>24 h) but not short time intervals after learning, highlighting the role of memory consolidation processes and sleep in dopaminergic modulation of memory traces (See Box 2 on the role of sleep in consolidation; Perogamvros and Schwartz, 2012).…”

Facilitation of fear extinction by novelty depends on dopamine acting on D1-subtype dopamine receptors in hippocampus

“…For this, we studied the role of hippocampal protein synthesis on the extinction facilitation by novelty through bilateral infusion into the CA1 region of the hippocampus of the protein synthesis inhibitor anisomycin (ANI) (12,13) after exposing the animals to the novelty. In addition, we examined the influence of hippocampal dopamine on this effect, in particular whether it is mediated by D1 or D5 receptors.…”

“…This influence is explainable by interactions between new proteins, called plasticity-related proteins (PRPs), at the two sets of synapses; the PRPs that tag one of them can be captured by those of others and enhance their responsiveness (3)(4)(5). Many memories rely on hippocampal LTP and LTD (1,2,(6)(7)(8)(9)(10)(11), and the "synaptic tagging-and-capture" process has been applied to the explanation of interactions between concurrent memories (11)(12)(13), among which are novelty and fear acquisition (12,14) and novelty and fear extinction (15,16). Exposure to novelty [an open field (OF) in which they had never been before] involves two consecutive processes: its detection, which is very brief (seconds), and the immediately ensuing habituation (17), which lasts much longer; both rely on hippocampal LTD (18).…”