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Headlines 7 Perhaps not surprisingly, research quickly identified different types of neurons in these regions that strikingly reflect space; from the “place” cells of the hippocampus that fire only in specific locations within a spatial context, to other types of cells in the entorhinal cortex that seem to represent space from an egocentric point of view -- a map centred on an animal’s location and facing -- and not an allosteric map centred on external coordinates. Clearly, the hippocampus and entorhinal cortex are special regions linked to the very essence of the concept of self; the ability to remember things that happen, and the ability to locate oneself in space. The goal of my research has been to understand how the functions of navigation and memory are linked, and ultimately to understand why these systems go wrong in disorders, with the goal of gaining insight into what it means to have a “self” and, more immediately, to help understand how we might attempt to address the disorders of memory that are so devastating to individuals who suffer from them, and their families. My initial doctoral work at Otago University with Professor David Bilkey focussed on how the hippocampus, so often thought of as coding space, can code for time. Together, we found that the hippocampus codes for time on very long timescales of at least a day. Critically, as with its representation of space, the hippocampus seems to code time not with reference to external variables like sunlight, but with reference to an internal event; in the case of my experiments at Otago, the availability of particularly palatable food. After my PhD, I was lucky enough to join the lab of Lisa Giocomo at Stanford, so I moved to California for my postdoctoral work. My work at Stanford has involved recording single neurons in the entorhinal cortex that have functions strikingly like those used to orient and measure distance in the external world. In this region, there are the “speed” cells that function like the speedometer of a car - how fast they fire is based on how fast you move. There are “head direction” cells that work like a compass, firing selectively only when you face a particular direction. Famously, this region also contains “grid” cells that fire in repeating patterns that function like a latitude/longitude coordinate system, functioning like an odometer letting you know how far you have gone. These cell types seem to represent all of the facets necessary to enable navigation, but until now it has been very unclear how they work together. In a paper about the project generously supported by the Neurological Foundation and published this January in Nature Neuroscience, I showed that the grid cells and speed cells in the entorhinal cortex are intrinsically linked - when an environment changes, they change together, and in the same way. On the other hand, I showed that head direction cells remain steadfastly independent, changing their firing in a way that seems to show that they reflect learned information, not that an environment has changed, but that it can change. In this study we also used a genetic knockout of a specific family of ion channels in the brain and showed that in these animals the grid cells are insensitive to changes in the environment. Critically, in these knockout animals, the speed signal is practically absent, and the cells that do code for speed do not change in response to environmental changes. However, the directional cells in these animals still respond in the same way as normal animals, further underlying the independence of the directional signal from the other types of cells in the entorhinal cortex. These findings were somewhat in line with current theories of grid cell function - it is thought that speed cells and direction cells might work together to create a velocity signal and that this signal enables grid cells to compute movement of an animal. Our findings, by contrast, show that no such velocity signal exists within the entorhinal cortex. However, we know that the directional signal begins much earlier, in the brainstem, and ascends to higher cortical regions while branching off, tree-like, into other regions. It’s possible that the directional part of a velocity signal might come from a region external to the entorhinal cortex. This finding suggests that key parts of the function of the entorhinal cortex rely on other brain regions to function, potentially expanding our list of regions to investigate when we study memory. These findings advance our knowledge of how the brain regions supporting memory work together, and give us new insights into how these critical regions function. With this publication, I found myself in a competitive position to apply for an academic position to lead my own laboratory, and I now live in Galway, Ireland where I lead my own research team, still studying learning and memory. I collaborate with H. Craig Heller at Stanford to study a mouse model of Down Syndrome, and I am now able to expand my research to study a long-held interest of mine: the link between disorders of eating and disorders of mood. I’m pretty sure the answer is in the hippocampus (although I admit I am biased!). I am extremely grateful to the Neurological Foundation and its generous supporters that enabled me to work on this project, and to succeed in my academic career. I hope that my research advances the aims of both the Foundation and its supporters, and I am confident that the investment made in my early career will pay off as my group makes new discoveries.