The things that I do well...

  • My work is directed towards understanding the neural basis of learning and memory.
  • As such, I have focused on the hippocampus system.
  • Resting in the medial temporal region, the hippocampal system includes the hippocampus proper, the dentate-gyrus, the subiculum and the overlying entorhinal and perirhinal cortices.
  • These temporal structures first drew the attention of memory researchers with the report of H.M., a then young man, who underwent the surgical removal of large portions of both hippocampi, amygdalae and overlying cortex in the early 1950s and subsequently suffered a permament and severe antergrade amnesia. Today, the hippocampal formation and overlying cortices continue to draw attention as the primary targets of neurodegenerative diseases such as Alzheimer's.
  • The hippocampal formation is one of the most plastic brain regions, attested to by being the primary site for the vast majority of Long-term potentiation (LTP) research as well as the original site of discovery.
  • The hippocampal formation also the primary site for the robust "spatial" signal best represented by place cells.
  • My primary approach uses electrophysiological recording techniques to capture the spontaneous and evoked activity from these structures.
  • Much of my work has also involved the induction of synaptic plasticity phenomena such as Kindling and the many forms of LTP.
  • For the last decade, I have focused on single cell, or "extracellular unit" recording from within the hippocampus and related cortices, exploring the navigational properties exhibited by many of the units or "Place Cells" and most recently by "grid cells".
  • This work culminated in a number of "Multi-site ensemble" recording studies, where I simultaneously captured the individual unit activity of many cells from multiple recording sites. In particular, recording from CA1 and any of the lateral entorhinal cortex and perirhinal cortex, or the medial entorhinal cortex and the pre- and para- subiculum. These cortices are the major inputs and outputs of the hippocampus proper, and thus, I have been tracing the neural spatial signal both forwards to and backwards throughout the hippocampal formation. As such, "Multi-site ensemble" recording is one of the newest, and most powerful techniques to provide insights into brain function.
  • In fact, the scientific publication Nature (download PDF 287KB) has featured this promising technique in one of its news articles as recently as July 2001.
  • As of July 2003, I joined the Suzuki lab at NYU, and have stepped up to recording from the non-human primate medial temporal lobe, primarily the entorhinal cortex, and hippocampus. Here, I have been able to successfully establish tetrode technology, along with local field potentials (LFPs).
  • Regardless of the recording technique, signal being studied, or synaptic phenomena being induced, I have specialized in the use of intact, awake behaving subjects.
  • Many people study synaptic plasticity in much reduced preparations like the hippocampal slice or cultured neurons. Although these methods have the advantage of providing quick initial answers to mechanistic questions, many of these findings will have to be demonstrated in the intact and behaving animal to verify their relevancy.
  • Recording from behaving animals brings with it numerous challenges not easily met or even understood by most. Much of my early work with LTP focused on how to overcome these challenges and avoid the pitfalls that plaqued the initial work relating LTP to learning. In addition to meeting the special needs of recording from behaving animals, I have developed an expertise in general rodent behavior, and specifically learning.
  • Typically this means knowing a bunch of experimental tasks, and I have employed my fair share of radial-arm and water mazes. Yet, I have also taken great care to observe and test many spontaneous behaviors. Overall my behavioral approach is akin to applying a neuropsychological assessment battery.
  • I have used this behavioral approach in a number of purely pharmacological studies that have tested the normalcy of behavior, with an eye to sorting out specific memory impairments from more global performance deficits.
  • In all the labs that I have worked, I have pioneered or established new techniques and analyses. I was the first individual to induce LTP at my graduate institution, which now boasts a number of LTP labs. I was the first individual to implement tetrodes in Canada and the first to establish primed-burst potentiation in the dentate gyrus during my first post-doctoral position in Montreal. I was one of the first three individuals to successfully accomplish multi-site ensemble recording of the entorhinal cortex and CA1, along with Loren Frank at MIT and the Moser group in Norway. Most recently, I was the second individual to establish tetrode recordings in the medial temporal lobe of non-human primates, next to Bill Skaggs of the McNaughton group.
  • To summarize, my goal is to understand the neural basis of learning and memory. In acheiving this goal I induce synaptic plasticity phenomena and employ numerous recording techniques to examine the impact of my manipulations at a systems level. I have concentrated these techniques and phenomena within the hippocampal formation. My work is carried out in intact behaving animals and therefore necessarily rests upon a strong behavioral and ethological foundation.

    Eric L. Hargreaves