Almut Hupbach - US grants

The extent to which memory preserves an accurate record of the past has been debated for over a century. The veridical memory view assumes that once memory consolidation is complete, memory is stable and no longer subject to change. Furthermore, the neurobiological processes responsible for consolidation involve strengthening, but not modification of a memory. Others have argued that memories are not fixed, but instead are transformed over time as a function of experience. Mounting evidence suggests that when memories are reactivated they become labile and open to change. Retrieval can reinforce the reactivated memory, or update it through the incorporation of new information. Such transformed memories then undergo a time-dependent re-consolidation process. Although the consolidation account, emphasizing strengthening and stabilization, was the de facto paradigm of research on memory dynamics in both psychology and neuroscience for many years, there is now increasing evidence that stable memory is the exception, not the rule. Until recently we have lacked experimental approaches to systematically address memory malleability, hence the mechanisms controlling memory updating remain obscure. Furthermore, despite the extensive literature on memory reconsolidation in animals, studies in humans are rare. Drs. Lynn Nadel, Rebecca Gomez, and Almut Hupbach at the University of Arizona have developed a research paradigm for investigating reconsolidation in episodic memory, a form of memory that allows for the conscious recollection of events. This research raises important questions having to do with whether updated memories are transient or long lasting and whether the effects occur only for new memories or for old memories as well. There is also the question of what factors trigger memory reactivation, whether these factors are affected by the strength of the original memory, whether the strength of these reminders diminishes over time, and whether implicit reminders differ from explicit ones in the extent to which they affect updating of an existing memory. With support from the National Science Foundation, Drs. Nadel, Gomez, and Hupbach will address these questions. They will conduct a series of experiments in which human volunteers will learn a set of objects and two days later will be reminded of the first session or not, then immediately afterwards will learn a second set of objects. After an additional two days, participants will be asked to recall the first set only. The extent to which reminded participants recall objects from the second set when trying to recall the first set, as compared to participants who are not reminded, is an index of memory reactivation and the subsequent reconsolidation effect.

Reconsolidation, and the underlying instability it reveals, demonstrates the essential transformative nature of memory systems and could help us understand a variety of memory malleability phenomena studied broadly in human cognition, as well as the updating of prior knowledge more generally. The work will explore conditions under which memory reconsolidation is observed in human episodic memory and would support the view that memories are dynamic, not fixed, and that they can be changed as a function of subsequent experience. The work will further show how such updating is affected by the age of a memory, by the nature of the reactivating event, and by the way in which memory itself is accessed at some subsequent time. Such details will begin the process of defining the critical determinants of human episodic memory dynamics. Knowledge about how memory is changed over time, and by experience, has profound implications for everyday life, influencing assumptions made within legal and clinical settings about what counts as normal memory. Understanding memory dynamics is also important for identifying the conditions affecting the updating of prior knowledge in learning and cognitive development, both in early childhood and across the lifespan. Understanding such conditions could have a profound effect on theories of cognitive change, on understanding when normal change goes awry and could also have implications for learning in educational practice.

Individuals differ greatly in their cognitive and creative abilities. Naturally occurring genetic variations are assumed to account for a significant proportion of these differences. The investigators will assess how naturally occurring variations in one gene family, the lynx genes, relate to cognitive and emotional functions in humans. Lynx gene variations alter brain function and cognitive and emotional behavior in mice model; this exploratory project addresses the link between lynx gene and behavior in humans. Results could inform the development of new therapeutic approaches for the treatment of cognitive impairments, such as those associated with Alzheimer's Disease, or observed after brain injury. The project could furthermore uncover the role of genetic factors for creative and artistic abilities and anxiety disorders. This in turn could help destigmatize mental disorders by providing a neurobiological basis for them and undergraduate students will be involved in every step of the scientific research process. The researchers are committed to increasing the representation of women and underrepresented minorities in STEM fields and will coordinate recruitment activities accordingly.

Candidate genes have been identified in mouse models that regulate neuronal plasticity and influence cognitive and emotional behavior. This project aims to test how naturally occurring variations in these genes, lynx1 and lynx2, relate to inter-individual differences in cognitive and emotional functions in humans. A large number of individuals will be screened for single nucleotide polymorphisms (SNPs) and tested on a variety of cognitive and control measures in order to develop unique cognitive profiles of individuals harboring mutations in these genes. Predicted differences in fear learning and memory updating will be tested by comparing performance of individuals with and without SNPs in aversive conditioning and memory updating paradigms. The project is the first one to assess how lynx gene variations relate to cognitive and emotional functions in humans, and is therefore exploratory, but has the potential to uncover important biological pathways impinging on complex human cognition.