Q&A with Lynn Nadel
Over the last several decades, research led by cognitive neuroscientists has led to new understanding of the hippocampus and its core role in human memory. “The attention the hippocampus has received, and the progress that has been made in understanding it, has been nothing short of astounding in the 50+ years since I first worked on it as a graduate student,” says Lynn Nadel of the University of Arizona.
Nadel’s work in particular has established how the hippocampus creates “cognitive maps” to represent context, allowing us to take actions even when distanced by time or space. His work has also led to new explorations of how hippocampal dysfunction may manifest in various neurological disorders, as well as new pathways for treatment through psychotherapy. For this body of work, Nadel is receiving the George A. Miller Prize in Cognitive Neuroscience at the CNS 2024 meeting this April in Toronto. We spoke with Nadel about his start in this research field, new findings on the hippocampus, and the translational aspects of the work, as well as what he’s looking forward to at the CNS annual meeting.
CNS: How did you first get started studying the hippocampus?
Nadel: As a graduate student at McGill University in the mid 1960s, it was impossible to avoid the hippocampus and memory. Brenda Milner at the Neuro (the Montreal Neurological Institute – MNI) and her Psychology PhD student Sue Corkin were studying the patient H.M., and Psychology Department Head D.O. Hebb had proposed his famous notions of cell assemblies, phase sequences, and what has become known as Hebbian learning at the synaptic level. Almost all of the graduate students in my cohort were interested in memory, and many were working on the hippocampus. My dissertation was focused on the possibility that there were differences in function between the dorsal and ventral hippocampus in rats – a possibility that has been borne out in recent decades.
CNS: What is a good example of how “cognitive maps” work in real life?
Nadel: In explaining the notion of cognitive maps I remind people of a time when they first visited and explored a new city, and how, over time, they acquired knowledge of where various important places were located in relation to one another. I point out that this knowledge is acquired slowly, over multiple episodes, and that they then use it to find their way around, even to take novel routes when detours are required because of construction, or traffic. If pushed, I point out that because these maps are developed in the hippocampus across multiple episodes this brain structure also seems central to episodic memory – that is, to storing knowledge about the sequence of things that happened in a particular location on a specific occasion.
CNS: What new findings are you most excited by and why?
Nadel: In my own work, I’m particularly excited about our current projects on memory updating, and the mechanisms driving this adaptive function. We are currently looking at the updating of memory “scripts”, and the possible role that the locus coeruleus plays in driving the dynamics behind memory updating. In a related sense, we are also looking at the importance of details in episodic memory, and why dysfunction in the hippocampal system typically results in a loss of access to details from episodes in the recent and remote past. One piece of this work involves asking what kinds of details lend credibility to the stories one tells about one’s past. Along with my former student and now collaborator Kate Simon we have determined that certain kinds of details make stories more believable.
CNS: Are there translational aspects of your work you can discuss?
Nadel: Indeed there are. The hippocampal system undergoes significant postnatal maturation, and many of its functions emerge only after months or years, depending on the species In particular, learning about places and contexts develops late.
Many years ago I started looking into the implications of this late maturation, focusing on what it means to start life without these capabilities. This led me to the idea that prolonged development might make the hippocampus particularly susceptible to perturbations caused either by atypical experiences or atypical genetics early in life. And this in turn led me to speculate, in the 1980s, that the mental retardation observed in Down syndrome (trisomy 21) might partly result from impaired hippocampal development. Work in both my lab and others subsequently supported this idea.
Another facet of my focus on early development was an exploration of the implications of early learning being relatively unbound to context, given the delayed maturation of its neural substrate – the hippocampal system. Jake Jacobs and I speculated that this early learning might re-emerge later in life in a particularly strong fashion, as it was untethered to specific contexts, and hence would generalize broadly. This in turn led us to formulate ideas about various anxiety disorders such as panic attacks, generalized anxiety disorder, and PTSD.
On a separate note, my more recent work on memory reconsolidation and updating has led to ideas, developed in collaboration with Richard Lane, Les Greenberg and Lee Ryan, about why and how psychotherapy might bring about enduring change. And finally, the work I alluded to concerning believability of stories has potential implications for navigating the world of disinformation we are now living in.
CNS: What do you most want cognitive neuroscientists to understand about the work you are doing?
Nadel: That paying attention to concepts and theories is critical to making progress, and sets the stage for doing meaningful experiments.
CNS: What do you most want the public to understand about what you are doing?
Nadel: That the work we do as scientists is relevant to their everyday life, and critically so in the world we now live in.
CNS: What are you most excited about for the CNS 2024 meeting in Toronto?
Nadel: Hearing about the latest work in the field is bound to be a highlight, especially when it provides an opportunity to meet younger colleagues, which in my case means just about everyone. I’m also excited about being able to revisit Toronto, where I have many good friends, including my long-time collaborator Morris Moscovitch. And I can’t help mentioning the fact that Toronto is an incredible international city with fabulous food and good museums.
CNS: Anything else you’d like to add that I did not ask about?
Nadel: You didn’t ask what it felt like to receive the George A. Miller Prize. The short answer is that it felt like, and is, a great honor to be associated with Miller, whose contributions to our field were immense. I first met him in the late 1980s, when our program at Arizona was being considered for one of the initial Cognitive Neuroscience Center grants from the McDonnell-Pew Foundation program that George Miller helped to spearhead. But I of course had known about him for decades, having read his 1960 book Plans and the Structure of Behavior as a graduate student. This book had a strong impact on me, since he and his co-authors (Galanter and Pribram) were clearly talking about the brain in a cognitive way, indeed in a way that linked up to Tolman’s cognitive maps and the expectations they generated. All this came back some years later when the idea that the hippocampus might be the substrate for cognitive maps emerged from O’Keefe’s 1971 discovery of place cells and our creation of the cognitive map theory of hippocampal function. To close that circle now, with this linkage to George Miller, is especially gratifying.
-Lisa M.P. Munoz