Conference Agenda

The integration of novel information into long-term memory can be promoted by presenting it within a known semantic context. For instance, acquiring new vocabulary in a foreign language is easier when it can be linked to pre-existing knowledge. This behavioral effect, also known as schema-dependent memory formation, has been demonstrated with various stimulus materials and across different species. Neurobiological models suggest that functional connectivity changes between the medial temporal lobe (MTL) and prefrontal cortex (PFC) promote the integration of novel information into existing knowledge structures, but several fundamental questions remain unresolved. This symposium aims to address these open questions by bringing together interdisciplinary research from both human and animal studies. More specifically, we will examine (a) the role of neurotransmitters, with a particular focus on dopamine, and their modulatory effects in the context of schema-dependent learning, (b) potential age-related changes, (c) the distinct neural mechanisms involved in encoding, consolidation, and retrieval, as well as (d) the interplay between novelty and prior knowledge. Taken together, the goal of this symposium is to discuss current views of schema-dependent memory formation, highlight its behavioral relevance across the adult lifespan and pinpointing underlying neural processes to refine future research.

When incoming information aligns with prior knowledge, it is processed, recognized, or recalled more efficiently. This phenomenon is known as semantic “congruency effect” and can be regarded as an example of schema-dependent learning. In this talk, I will present results from a series of behavioral and imaging experiments showing that, on a behavioral level, the congruency effect is well preserved in healthy older adults and modulated by dopamine. On a neural level, the congruency effect was associated with hemodynamic activity within CA3, and this hippocampal subfield showed enhanced functional connectivity to the laterobasal amygdala. In a pharmacological fMRI study, the congruency effect was highest under placebo and significantly reduced by a dopamine agonist (1.25 mg bromocriptine) and dopamine antagonist (400 mg sulpiride). Compatible with this observation, subsequent memory effects in the left inferior frontal gyrus and its connectivity with the left substantia nigra and right nucleus accumbens, respectively, were also modulated by drug in a quadratic fashion resembling the behavioral pattern. Taken together, these findings give novel insights by suggesting that schema-dependent learning is preserved across the adult lifespan, and it is modulated by prefrontal dopamine and interconnected mesolimbic regions.

Previous knowledge, structured as a cognitive map, facilitates knowledge acquisition and shapes the learning of new spatial information. The Mouse HexMaze, a novel behavioral task, enables the study of complex memory processes such as schema formation and updating. In this large (2m × 2m) environment, mice learn to navigate efficiently to a rewarded location over an extended period. When new information is integrated within an existing knowledge framework, memories become hippocampus-independent within 48 hours, as demonstrated by pharmacological inhibition of AMPA receptors. However, memory encoding in the presence of prior knowledge remains hippocampus-dependent. To investigate the persistence and reorganization of memory traces, we employed histological analysis using cFos-TRAP2 mice, enabling in vivo tagging of the initial memory engram. Comparisons between the original engram and cFos-expressing populations at two weeks and three months post-training revealed more than 50% overlap, suggesting that memory updating relies on the preexisting cortical representation as a scaffold. Despite pharmacological inhibition of the prelimbic and retrosplenial cortices separately, task performance remained unaffected, indicating the formation of a robust and distributed memory network.

Prior knowledge in a given domain, often referred to as a schema, strongly influences how we encode and integrate novel information, even when that information is neutral with respect to schema-driven expectations (i.e., neither congruent nor incongruent). This assimilation has been attributed to more effective organizational processing, facilitating referential connections within the activated associative schema network. Animal studies suggest that the systems consolidation of such assimilated information is also accelerated.

In two fMRI studies employing distinct schema operationalizations, we provide further evidence for these mechanisms and elucidate their neural underpinnings. Our findings consistently show enhanced vmPFC-hippocampus coupling during the encoding of schema-related information, supporting a prior-knowledge effect that is distinct from schema congruency or incongruency. Moreover, a combination of multivariate and univariate analyses highlights the contributions of the vmPFC, precuneus, and angular gyrus in the efficient encoding of schema-related information. Additionally, our results provide further evidence for the accelerated systems consolidation of novel, schema-related, and potentially assimilated information.