Tomás Ryan’s research focuses on the fundamental biology of memory storage in the brain. Recent studies have shown that spatial memories are encoded as sparse populations of cells that are activated during learning and are necessary for the retrieval of specific memories. These cells can be operationally defined as “memory engram cells” and the focus of Ryan’s research is to understand how engram cells are able to store specific memories as information. To address this question the Ryan group engages in experimental studies of memory encoding, storage, and retrieval in the mouse. The approach is experimental and interdisciplinary, including behavioral neuroscience, optogenetics, engram labeling technology, electrophysiology, calcium imaging, and molecular genetics.
My plans for the fellowship period
All humans experience amnesia. While 33% of adults in the developed world population who live to be over 65 years of age will suffer from some form of dementia, 100% of the human population experience infantile amnesia, which is the loss of memories formed in early childhood (prior to 2–4 years). Though infantile amnesia is likely the cost of crucial cognitive developmental processes, it is also a constraint and limitation on education and learning during the formative years. Infantile amnesia is conserved across the mammalian kingdom, and indeed mice have been shown to display infantile amnesia. But little is known about the underlying neurobiology.
Amnesia in general is characterized by an apparent loss of memory, but the underlying cause of a given type of amnesia is shrouded in ambiguity. By assessing amnesia solely on the behavioral or cognitive performance of a subject it is not possible to discriminate between the possibility that memory information has been truly lost from the brain (a memory storage deficit) and the alternative possibility that the memory is still present in the brain but is not fully accessible (a memory retrieval deficit).
I have recently developed an experimental framework that allows for the discrimination of these two possibilities by employing memory engram labelling technology. Memory engrams are the sites of learned information in the brain, and are composed of ensembles of brain cells. By genetically tagging engram cells with optogenetic receptors, we can directly activate specific memories at will in an awake behaving mouse. I was able to show that forms of amnesia in adults are in fact deficits of memory retrieval. Though the memory appeared to be lost due to amnesia, direct activation of engram cells caused its retrieval. During my fellowship I will apply and develop this framework to investigate infantile amnesia in rodent models.
How will my work change children’s and youth’s lives?
Early childhood is a time of rapid brain development and enormous neural plasticity. It is also when people first comprehend language and construct their basic schemas of the world on which education is built. Yet it is also a time of widespread forgetting. Virtually all episodic memories formed in the first 2-4 years of life are lost after the individual enters later childhood and remain lost through to adulthood. Infantile amnesia thus represents the most pervasive and ubiquitous form of amnesia in the human population. Its ubiquity may account for society’s acceptance of it – because it’s always been there and everyone experiences it, it may be regarded as a fact of life that we must suffer. But what if we could circumvent infantile amnesia and allow our earliest memories to develop steadily throughout development? Could this allow us to develop an entirely new educational paradigm? It has recently been demonstrated that other forms of adult amnesia are in fact due to memory retrieval or access deficits, where the memory information survives through the experience of amnesia but is “locked in” to the brain. Early clues suggest this may also be the case for infantile amnesia. I will investigate the neurobiology of infantile amnesia by studying memory engram neurobiology in rodent models. If the presence of infant memories can be demonstrated in adult subjects, then it may be possible to retrieve them and perhaps to prevent infantile amnesia for certain memories altogether. Such findings would open many new doors for the exploration of novel educational approaches for the development of knowledge schemas in children.