What are the mechanisms behind human learning? Achieving a better understanding of this complex question is not just an academic pursuit, given the prevalence of neurological conditions such as Alzheimer's disease and dementia. Indeed, this line of research could bring significant benefits for Europe's ageing population, including treatments for conditions that lead to memory loss.
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The EU-funded Fear Memory Trace project, which is seeking to push scientific understanding in this field, represents an important step in this direction. By providing new experimental data at the neurophysiological level, along with novel computational tools to make predictions about how people acquire – and lose – memories, the project could open the door to new treatments for certain neurological conditions.
"Both of these project outcomes should further our knowledge of the mechanisms of memory acquisition and allocation, and advance our understanding on how multiple memories can be stored in the brain," explains Dr Kiki Sidiropoulou, a Marie Curie Fellow who is leading the work on this project.
The development of computer models capable of assessing the role of these mechanisms in memory performance in particular represents a critical breakthrough, as it will allow researchers to carry out new tests and experiments. As Europe's population ages and memory-debilitating conditions increase, such research could prove highly significant.
Understanding how neural mechanisms – the ways in which cells process and transmit information – allow us to store, find and even forget memories, is crucial to understanding how conditions such as Alzheimer's begin. The onset of such conditions can have tragic consequences, leading some patients to forget the faces of their own family, or remain trapped in the memories of a difficult period in their lives. Developing effective treatments could have a positive impact on the quality of life of millions.
"We were interested in finding out how these mechanisms contribute to memory allocation, through experimentation and computational techniques," says Dr Sidiropoulou. "Our data and final results will provide a theoretical framework upon which researchers can make further advances to enhance our ability to acquire memories."
The aim of the project has been to identify how neural mechanisms are altered after the formation of specific memories. Memory allocation is a newly defined phase of the process, which refers to the recruitment of specific neurons in a network that will encode a specific memory.
Fear Memory Trace has investigated the synaptic properties – how information is passed – between neurons in the amygdala, the part of the brain which plays a key role in the processing of memory and emotional reactions. This has helped the researchers to determine the underlying biophysical mechanisms that allow neurons to compete with each other for encoding a specific memory.
An important part of the project has been the study of conditioned fear memory in mice. Building on previous research, the team knew this to be allocated and stored in the amygdala. They also knew that a particular protein plays a role in allocating memory to a specific group of neurons – meaning it is traceable. Neuronal excitability, the project team thought, could play a role.
The results of behavioural, electrophysiological (the study of electrical properties in cells) and modelling experiments gave scientists an insight into how neurons compete with each other for allocation to a specific memory. This has helped them to understand how, in practice, memories are stored.
"We have identified several changes in neurons that occur in response to two different learning paradigms," says Dr Sidiropoulou. "The first was a fear-conditioning learning task with which mice acquire a fear memory, and the second was a conditioned taste-aversion task with which mice acquired a memory to avoid a previously desirable taste." This enabled the research team to better understand how and where the fear memory is stored.
The project team is currently developing an abstract network model of how – and where –memories are stored. This will include several physiological parameters – information on the mechanical functions of the brain – as well the team's own data. The model will enable researchers to test the learning-induced changes on brain network behaviour, and our own ability to acquire and safeguard memories.