Johns Hopkins School of Medicine

Neurophysiology of Memory in the Hippocampal Formation

The hippocampus and medial temporal lobe structures are critically involved in episodic memory.  Our laboratory investigates the flow of information through the hippocampal formation and the computations performed by the various subfields of the hippocampus and its inputs from the entorhinal cortex. Our working model is that the lateral entorhinal cortex (LEC) provides the hippocampus with representations of items in the world "out there" from a first-person (egocentric) perspective; these representations convey the content of an episode.  In contrast, the medial entorhinal cortex (MEC) combines external landmarks with path integration to create an allocentric spatial map that conveys the spatiotemporal context of an episode. The hippocampus binds the egocentric content representations of the LEC with the allocentric content information of the MEC to form context-specific, content-addressable memories of the events of an organisms' life.  The various subfields of the hippocampus (the dentate gyrus and CA3, CA2, and CA1 pyramidal layers) each have specific computational roles and neural dynamics that optimize the storage capacity and recall accuracy of this memory system. 

To address how the hippocampal circuitry performs these tasks, we use multi-electrode arrays, silicon probes, optogenetic tagging, imaging techniques, and computational methods to record and analyze the extracellular action potentials and/or Ca++ activity from scores of well-isolated hippocampal and entorhinal neurons in freely moving rats and mice. Hippocampal 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). Medial entorhinal "grid cells" fire in an exquisite, hexagonally arranged spatial pattern.  The discoverers of these 2 cell types earned a Nobel Prize in Physiology or Medicine 2014. These cells constitute a tremendous opportunity to investigate the mechanisms by which the brain transforms sensory input into an internal, cognitive representation of the world "out there" and then uses this representation as the framework that organizes and stores memories of past events and allows the subsequent retrieval of these memories to be brought to consciousness.