Jon Wilson @jonjwilson@qoto.org

I will start this hippocampal 'history tour' with the contribution from Carolyn Harley. For those of you who did not know Carolyn (who passed away several moths ago) I will preface her thoughts by noting that she was an absolute gem of a scientist and person. Always cheerful, always helpful, and always curious. The past few years I was lucky enough to engage in weekly conversations with her (and recently including a few younger colleagues) to discuss the role of the locus coeruleus in modulating hippocmpal memory dynamics. Sadly our efforts though close to being publishable are now going to have to be finished up without her always thoughtful input.

With that as an introduction, here is what Carolyn had to say in response to the questions I posed:

1. What got you interested in the hippocampus? My supervisor, Dan Kimble, because of Dan’s lectures at the UO decades ago I switched my graduate studies plan from cross-cultural psychology to physiological psychology (as it was then called). His research interest was the hippocampus and he had studied with Bob Isaacson and spent postdoctoral time with Karl Pribram at Stanford. Because of his sojourn there I later had a chance to spend a summer in Chile with Theresa Pinto-Hamuy who had been with Dan at Stanford and who also deepened my interest in the biology of learning and memory more broadly. As a graduate student I spent a lot of time looking at rats with bilateral suction lesions of the hippocampus. We observed their maternal behaviour, sexual behaviour, orienting behaviour, dominance behaviour as well as testing them on various learning and memory tasks. I was struck by how relatively subtle the differences were. I tested the role of the hippocampus in attentional shifting for my PhD thesis but failed to support the hypothesis I was testing. Dan had predicted deficits in inhibiting attention to previously significant cues and I did not see such deficits. My most interesting results, failure to orient to a novel stimulus when competing stimuli were present, and fixated position responding when behavioural shifts were required in difficult learning tasks, could be explained, we then suggested, by subjects being prone to frustrative fixated behaviour patterns because they lacked inhibitory control over energizing hypothalamic systems. At a later time in my career as I turned to experiments involving the role of the locus coeruleus in modulating hippocampal input and in learning and memory I was struck by how similar the deficits after hippocampal lesions were to deficits after LC lesions. There is a link there somewhere. In any event by the end of my PhD thesis I thought the only way forward was to record from hippocampal neurons in behaving rats. I didn’t have the opportunity at that time for various personal reasons, but you will know from that observation what were the findings in the past 50 years that most excited me.

2. Aside from your own work, what findings about hippocampus (and related brain parts) in the past 50 years most excited you, and why? The findings showing that the hippocampus provides spatial, and likely, temporal structures to frame our episodic memories have most excited me. The idea of the transfer of individual life events to cortical encoding semantic records also had a revelatory quality for me.

3. Can you relate one personal story about interactions with colleagues that most exemplifies the world of hippocampal research? As a relatively young researcher in a relatively isolated university, the most amazing thing that happened to me, which I think exemplifies the world of hippocampal research, was when my husband wanted me to go to London for my sabbatical as he was interested in the poetry community there. By that time, the O’Keefe and Nadel book has appeared to revolutionize our thinking. With a friend, I had organized a senior seminar around that book and related findings. I had met John O’Keefe briefly at conferences but never had a real conversation with him. Of course that would have been my own dream sabbatical. So with spousal encouragement I phoned his UK lab (the Cerebral Functions Group as he had grandly named it) from Newfoundland to ask if I might spend a year there. He was so immediately encouraging (even seeming to know who I was) and welcoming that I was at lost for words. I spent a wonderful year in the UK and the very first experimental results he showed me were his first evidence that a hippocampal map provides a look at what the rat is thinking. He could predict the choices that would be made in a cue-less environment based on the map that had been called up earlier in the presence of cues (O’Keefe and Speakman Exp Brain Res. 1987;68(1):1-27). Andrew was still in the lab working on the data when I arrived. It was a glorious time and no experiment has ever made more of an impression on me than that did. Imagine looking at the brain and inferring accurately what another species is thinking and feeling that you understand why they do what they do subsequently. Listening to cells that year was all that I had hoped it would be. Despite John’s best efforts to design a poor lady’s Microdrive for me to take home, we only carried out a few experiments with stereotrode technology at my home University. (It did lead to an MSc thesis for John Huxter, who returned to John’s lab to work on phase precession.) But I think the poor lady’s Microdrive became the basis for the drives used by Kate Jeffries and Axona. Pat Wall and Clifford Woolf were also in the group at that time. They all shared as generously of their thoughts and their time as John and I also brought home new methods acquired from Cliff that led me to a better understanding of brain compartments and the suite of brain metabolic responses. Alan Ainsworth, John’s electrophysiological technician, was also wonderfully helpful. It was such a welcoming small group from top to bottom. I would run into Bernard Katz in the library and attended a rich assortment of local and visiting lectures, but it is the time in the informal (sneakers hung on the wall) environment of continual thought and discussion that has stayed with me most. It was so exciting. It is still my impression that the world of hippocampal researchers is a most welcoming one.

4. What would tell a young researcher interested in the hippocampus to focus on now?

I guess I see two rather different directions that would be exciting as foci for me if I were again a young researcher. One is to go in a network direction and look at what conversations are being held between the hippocampus and its subfields and other brain regions. The other is to ask more focused questions about the creation and support of hippocampal memories of varying durations. There are terrific new tools to investigate in both those directions or in any direction that captures your imagination. I began my studies of locus coeruleus/hippocampal interactions with the idea that I would come to include all the neuromodulatory hippocampal inputs and define their interactions as well as their roles in ‘isolation’ (if that ever happens). I am still finding new depths in that single input so must leave the larger conversation to others. It is an endlessly fascinating topic.