Speakers:

Graham Collingridge, University of Toronto, University of Bristol, UK

Roger A. Nicoll, University of California, USA

CaMKII and LTP

Abstract: CaMKII and long-term potentiation (LTP) were discovered within a decade of each other and have been inextricably intertwined ever since. Francis Crick proposed that a memory molecule should possess two properties. First, it should be a multimeric protein with identical subunits that can phosphorylate each other. Second, to address how memories outlast molecular turnover he proposed that naïve unphosphorylated subunits could exchange into the phosphorylated multimer and become phosphorylated. In my talk I will demonstrate that autophosphorylation of CaMKII, indeed, maintains LTP (memory) by the synaptic capture of AMPA receptors and that this memory survives the protein turnover of CaMKII.

Todd Sacktor, SUNY Downstate Health Sciences University, USA

Ole Paulson, University of Cambridge, UK

Linking past and present: Associative properties of LTP

Abstract: Long-term potentiation of synaptic transmission (LTP) is a strong candidate for a cellular mechanism mediating memory formation in the mammalian brain. The associative properties of LTP were quickly recognised and, indeed, LTP is thought to underlie several forms of associative learning. However, associating events that occur with a temporal gap, for example between a stimulus or action and later reward, has been difficult to explain at the cellular level. In this presentation I will argue that hippocampal LTP has properties that can help explain how brain networks overcome the challenge of bridging the temporal gap in neural activity between action and reward, known as the distal reward problem. Specifically, I will show that hippocampal synaptic activity can leave an NMDA receptor-dependent silent eligibility trace which seconds or even minutes later may be converted into overt potentiation by the coincidence of the reward signal dopamine with a postsynaptic calcium spike. The underlying molecular mechanism involves a calcium-regulated adenylyl cyclase and protein kinase A. This synaptic learning rule suggests that neuromodulation by dopamine may help bridge the time scales of synaptic plasticity and behavioural learning and memory.

Dorothy Tse, Edge Hill University, UK

The Effects of Novelty and Prior Knowledge on Memory

Abstract: Memory formation is influenced by various factors, such as novelty and prior knowledge. While we often recall information more easily when it connects to what we already know, novel experiences can also be highly memorable. This talk explores how these two factors shape memory encoding.

Using an animal model, we investigated how novelty - experienced either before or after encoding - affects memory retention. Our findings show that novelty significantly enhances retention, suggesting its critical role in strengthening memory. Optogenetic activation of the locus coeruleus produced similar enhancements and led to a slow-onset potentiation of hippocampal CA1 field potentials. Interestingly, although the locus coeruleus is primarily associated with noradrenergic activity, these effects were blocked by the dopamine D1/D5 receptor antagonist SCH 23390, indicating a dopaminergic mechanism.

The role of prior knowledge was examined through a paired association learning task. Animal studies demonstrated that memory consolidation is accelerated when new information aligns with an existing schema. Extending this to human research, we developed a virtual shopping mall task where participants associate locations with objects. This study aims to reveal how schemas facilitate information assimilation and may provide insights into age-related navigation impairments. Preliminary findings will be discussed.