Cellular and Systems Mechanisms of L&M
Siena, Italy
June 1, 2017



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June 1, 2017
Richard Morris
Centre for Cognitive and Neural Systems
University of Edinburgh

1- Memory consolidation: synaptic tagging and schemas
A widely held model of memory encoding is activity-dependent synaptic plasticity, as studied in the physiological phenomena of long-term potentiation (LTP) and depression. Synaptic potentiation mediated by NMDA receptor triggered changes in AMPA receptor trafficking and expression has a number of features that make it an attractive storage mechanism, but the initial encoding of ‘traces’ at numerous synapses in a distributed associative memory system is no guarantee that they will last. This presentation will focus on two aspects of memory consolidation – cellular and systems. Cellular consolidation to help memory persistence involves a diverse set of interacting mechanisms including neuromodulatory transmitters, intracellular signal transduction pathways, gene activation etc. The synaptic tagging and capture model of protein synthesis-dependent synaptic potentiation offers a new framework for thinking about the timescale over which such cellular activity-dependent interactions may take place. In contrast, systems consolidation across diverse neural networks beyond the single cell involves additional mechanisms. Whereas this form of consolidation has sometimes been conceived as a process of ‘transferring’ information from one anatomical network to others, new research suggests that there may sometimes parallel encoding in neocortical and allocortical networks, with the activation of prior knowledge guiding the subsequent process of assimilation in a top-down manner.

2- Can what we yet know about learning and memory help in the search for new therapies for Alzheimer’s Disease?
We all know what Alzheimer’s Disease (AD) and the growing age-related burden it represents already. As an early indicator of incipient AD is the loss of recent memory, it is surely likely that what we have learned about the organization of memory systems in the brain could be helpful in tackling this area of biomedical uncertainty. However, the field remains dominated by its scientific heritage in neuropathology, in biochemistry and genetics, and does little more than pay lip-service to the possibility that ‘cognition’ could be a valuable addition to the biomarkers that are being explored in connection with understanding the disease. Of course, understanding, slowing down and eventually treating AD is an enormously difficult problem requiring an interdisciplinary approach – but I shall endeavor to illustrate some examples of work conducted with mouse models over the past 20 years that collectively represent a valuable contribution to the field. This will include some recent work from my group on the very early and preventive treatment of a mouse model of AD prior to deposition of beta-amyloid plaques. As part of this abstract, I invite everyone in the audience to write ‘yes’ or ‘no’ after the following statement: “The primary responsibility of scientists is to understand the world around us, but we should also not miss opportunities to pause to apply our understanding for the betterment of humankind”. Then let’s discuss!