Place Cells in the Hippocampal Formation

Work in our laboratory attempts to understand the flow of information through the hippocampal formation and the computations performed by the various subfields of the hippocampus. To address these issues, we use multi-electrode arrays to record the extracellular action potentials from scores of well-isolated hippocampal neurons in freely moving rats. These neurons have the fascinating property of being selectively active when the rat occupies restricted locations in its environment. They are termed “place cells,” and it has been suggested that these cells form a cognitive map of the environment (O’Keefe and Nadel, The hippocampus as a cognitive map). The animal uses this map to navigate efficiently in its environment and learn and remember important locations. It is also hypothesized that these cells play a major role in the formation of episodic (autobiographical) memories. Place cells thus constitute a tremendous opportunity to investigate the mechanisms by which the brain transforms sensory input into an abstract, cognitive representation of the world “out there” and then stores this representation in memory.

Although place cells have been studied for over 30 years, we are still in the initial stages of exploring and understanding these cells. The large majority of studies of place cells have concentrated on the CA1 region of the hippocampus. Comparatively little is known about the other areas of the hippocampus (CA3, dentate gyrus) or the entorhinal cortex. It is a guiding tenet of this laboratory that further progress in understanding how place cells are generated and utilized requires a deeper understanding of the other parts of the hippocampus and the structures that transmit information into the hippocampus. By recording many of these area simultaneously and performing various manipulations on the environment and the animal’s own internal state, we hope to decipher how these areas differ in their information processing functions and ultimate roles in guiding behavior and constructing memories. The major projects currently ongoing in the laboratory include the following:

(1) Are there attractor networks in the hippocampus? A number of computational theories have postulated that the hippocampal circuitry contains attractor neural network architecture and dynamics. Such properties would help explain phenomena such as the stability of place field firing patterns in the absence of sensory input; they would also serve as a possible substrate for associative memory and recall. The recurrent collateral system of CA3 makes it a more likely candidate to contain this attractor circuitry than CA1, and we have recently published a paper showing that CA3 cells show greater evidence than CA1 cells of being part of strong attractor networks (Lee et al. Nature 430:456-459, 2004).

(2) Are head direction cells parts of attractor networks? Even more so than place cells, current modeling and theoretical work suggest that the head direction cell circuit may form an attractor neural network. We are currently recording CA1 place cells and anterior thalamic head direction cells to test whether the head direction cell system shows evidence of stronger attractor dynamics than does the CA1 place cell system.

(3) What is the relationship between the hippocampal place cell system and the limbic Head Direction Cell system? Head direction cells, which serve as an internal compass for directional orientation, are a major input into the hippocampus and may be the major source of information that sets the orientation of the cognitive map relative to the external environment. We are investigating more closely the interactions between place cells and head direction cells in order to understand how they influence each other more precisely.

(4) Can hippocampal remapping be interpreted in terms of pattern separation/pattern completion processes? A number of investigators have hypothesized that the function of the dentate gyrus may be to perform pattern separation (orthogonalization) on hippocampal inputs, in order to make the subsequent representations in the hippocampus more independent and thus less susceptible to interference. Conversely, the function of CA3 has been postulated to be pattern completion, the ability to output a stored memory pattern when only a partial input (or a slightly modified input) is given to the system. The phenomenon of hippocampal remapping may be the result of a competition between these two processes in the hippocampus. By recording simultaneously from neurons in the CA1, CA3, and dentate gyrus regions of the hippocampus, we are studying quantitatively the patterns of remapping that occur with different environmental manipulations in order to test these long-held, but never rigorously investigated, theories of hippocampal function.

(5) What are the basic firing characteristics of the entorhinal cortex cells that form the major neocortical input to the hippocampus? Little is known about the spatial firing characteristics of the neurons in the superficial layers of the entorhinal cortex, even though these cells are the major cortical input into the hippocampus. We are investigating some key questions such as whether these cells are more tightly bound to the external sensory environment than are CA1 place cells, and whether there exist differences in the properties of cells in the Medial Entorhinal Area and the Lateral Entorhinal Area.