Research Interests and Publications:

What are memories made of?

Neuropsychologists divide memory into two main types:   explicit, or declarative memory, the conscious recollection of facts, events, and places; and the several kinds of   implicit memory (e.g. classical conditioning, motor learning) which do not require conscious awareness for recall.   Ever since the tragic case of H.M., it has been clear that the hippocampal formation is crucial to the acquisition of explicit memories.   Following bilateral lesion of his hippocampal formation, H.M. never again formed new explicit memories that lasted more than a few minutes.      

Our laboratory is interested in elucidating the cellular and molecular basis of hippocampus-based memory.   We utilize two complementary sets of techniques to achieve this end:   long-term extracellular recordings of neurons from the hippocampal formation of actively behaving rodents, and the generation of transgenic mice specifically designed for such recordings.  

When one records hippocampal neurons from behaving mammals, they act as "place" cells... that is, they fire when the animal occupies a particular region of its environment, termed the cell's firing field.   These firing fields form in minutes when the animal is put into a novel environment, and are specific to that environment.   In subsequent reintroductions to a given environment, the firing fields are generally stable (i.e. the cells have the same firing fields).   This place field stability is perhaps the most compelling reason to think that place cells are, in fact, neural correlates of spatial memories. Just like behavioral memory, place fields form based upon experience, and they are recalled in response to the appropriate stimuli.   A major focus of the laboratory is therefore the investigation of the determinants of place field stability, on both the molecular and cognitive levels.   For instance, earlier work found that molecular cascades implicated in in vitro hippocampal plasticity (i.e LTP) are also involved in place field stability.  On the more cognitive level, we have found that place field stability correlates with both performance in a spatial task and increased attention to (and indeed awareness of) the animal's spatial context.   This is precisely how one would expect neural correlates of spatial memory to behave.  Ultimately, the goal of the lab is to determine how these higher-order cognitive processes affect place field stability on a molecular level.

In parallel with these studies, we are also taking advantage of the anatomical specificity inherent to enhancer elements to dissect out the relative roles played by distinct elements of neural circuits.   This is being accomplished by inducibly expressing dominant negative transgenes in specific neuronal populations and recording upstream and downstream of the molecular lesion, both before and after transgene induction.   In this way we can learn the relative contribution of different elements of a neural circuit to the firing patterns of neurons within that circuit.

Selected Publications:

Kentros C., Agnihotri, NT, Streater, S., Hawkins RD., Kandel ER   (2004) "Increased Attention to Spatial Context Increases Both Place Field Stability and Spatial Memory."   Neuron (In Press for April 22nd Issue)

Agnihotri NT, Hawkins RD, Kandel ER, Kentros C. (2004) "The long-term stability of new hippocampal place fields requires new protein synthesis."   Proc Natl Acad Sci U S A . Mar 9; 101 (10):3656-61.

Kentros C, Hargreaves E, Hawkins RD, Kandel ER, Shapiro M, Muller RV. (1998)   "Abolition of long-term stability of new hippocampal place cell maps by NMDA receptor blockade." Science Jun 26; 280 (5372):2121-6.