Hippocampus最新文献

I have been incredibly fortunate to have worked in the field of hippocampal spatial coding during three of its most exciting decades, the 1990s, 2000s, and 2010s. During this time I had a ringside view of some of the foundational discoveries that were made which have transformed our understanding of the hippocampal system and its role in cognition (especially spatial cognition) and memory. These discoveries inspired me in my own lab over the years to pursue three broad lines of enquiry—3D spatial encoding, context and the sense of direction—which are outlined here. If some of my personal recollections are a little inaccurate (such is the nature of episodic memory!) I apologize in advance.

Two key series of discoveries about the hippocampus are described. One is the discovery of hippocampal spatial view cells in primates. This discovery opens the way to a much better understanding of human episodic memory, for episodic memory prototypically involves a memory of where people or objects or rewards have been seen in locations “out there” which could never be implemented by the place cells that encode the location of a rat or mouse. Further, spatial view cells are valuable for navigation using vision and viewed landmarks, and provide for much richer, vision-based, navigation than the place to place self-motion update performed by rats and mice who live in dark underground tunnels. Spatial view cells thus offer a revolution in our understanding of the functions of the hippocampus in memory and navigation in humans and other primates with well-developed foveate vision. The second discovery describes a computational theory of the hippocampal-neocortical memory system that includes the only quantitative theory of how information is recalled from the hippocampus to the neocortex. It is shown how foundations for this research were the discovery of reward neurons for food reward, and non-reward, in the primate orbitofrontal cortex, and representations of value including of monetary value in the human orbitofrontal cortex; and the discovery of face identity and face expression cells in the primate inferior temporal visual cortex and how they represent transform-invariant information. This research illustrates how in order to understand a brain computation, a whole series of integrated interdisciplinary discoveries is needed to build a theory of the operation of each neural system.

Because imagination activates the same neural circuits used in understanding the present, one can access that imagination even in non-linguistic animals through decoding techniques applied to large neural ensembles. This personal retrospective traces the history of the initial discovery that hippocampal theta sequences sweep forward to goals during moments of deliberation and discusses the history that was necessary to put ourselves in the position to recognize this signal. It also discusses how that discovery fits into the larger picture of hippocampal function and the concept of cognition as computation.

This contribution is part of the special issue on the Hippocampus focused on personal histories of advances in knowledge on the hippocampus and related structures. An account is offered of the author's role in the development of neural ensemble recording: stereo recording (stereotrodes, tetrodes) and the use of this approach to search for evidence of Hebb's “cell assemblies” and “phase sequences”, the holy grail of the neuroscience of learning and memory.

Here I describe how an interest in synaptic plasticity took me from a PhD at McGill, where I worked on activity-dependent plasticity in the responses of single units in the association cortex of anesthetized cats, to a collaboration with Terje Lømo in Per Andersen's laboratory in Oslo in 1968–9. There we followed up on Lømo's discovery of LTP, published as an abstract in 1966, to produce the first detailed description of the phenomenon. Later, in London, Tony Gardner-Medwin and I showed that LTP lasting for days could be obtained in the awake rabbit. The two papers were published together in the Journal of Physiology in 1973. I relate how difficulties in replicating our results in English rabbits, and the failure of the first attempts to obtain LTP in slices of the dentate gyrus, led to my abandoning work on LTP for a few years, returning to the fray in the late 1970s through a collaboration with Graham Goddard at Dalhousie University in Halifax, Canada.

The mandate for this special issue of Hippocampus was to provide a few examples of one's own work in a relatively personal context. Accordingly, I will discuss some of my own work here, but will also provide a broader arc of ideas and discoveries within which the efforts of myself and many others have taken place. This history begins with the associationists, who proposed that the human mind could be understood, in part, as a compounding of simple associations between contiguously occurring items and events. This idea was taken up by the behaviorist traditions, which made significant progress toward refining this simple idea. Subsequently, as interest turned toward neural mechanisms, Donald Hebb provided a foundational proposal for how synaptic changes could provide for this associative learning. The associationist view was, however, challenged by gestaltists who took a more wholistic, cognitive approach. Stunning support was provided for Tolman's cognitive map idea with the discovery of place cells in the hippocampus, and the subsequent treatise provided in O'Keefe and Nadel's The Hippocampus as a Cognitive Map. I propose that, ultimately, this associationist versus cognitive debate was settled by the development of the Parallel Distributed Processing (PDP) approach, which incorporated Hebbian synapses into large, neural-like networks, which could accomplish complex cognitive tasks. My own work took place within the framework provided by O'Keefe and Nadel. One aspect of my work followed Jim Ranck's discovery of Head Direction cells. Tad Blair and others in my lab traced a brainstem circuit, which we proposed could explain the origins of the directional code. In other work, I investigated cells in the subicular region. These provided a contrast to the hippocampal place cells in that each subicular cell kept the same spatial pattern across different environments, whereas the hippocampal cells formed a different map for each context.