The Center for Learning and Memory was established in May 1994 as an interdepartmental research center between the Department of Brain and Cognitive Sciences and Department of Biology. The Center's primary research interest is to study the mechanisms underlying learning and memory using multifaceted approaches. Susumu Tonegawa was appointed as the first Director of the Center in May 1994. Matthew A. Wilson joined as an Assistant Professor on July 1, 1994. William G. Quinn who has been a faculty member in Department of Brain and Cognitive Sciences since July 1, 1994 joined the Center on April 1, 1995. Guosong Liu and Earl Miller joined as Assistant Professors on September 1, 1996.
RESEARCH BY CENTER SCIENTISTS
Dr. Susumu Tonegawa's laboratory developed a novel genetic technology with which researchers can knockout a gene in specific neurons in the hippocampus, namely CA1 pyramidal cells. They applied this technology to an NMDA receptor gene and produced a mutant mouse strain in which this gene is deleted exclusively in the CA1 pyramidal cells. By analyzing these mice by brain slice electrophysiology and by behavioral methods, they obtained strong evidence for the notion that synaptic plasticity underlies spatial learning.
Dr. Matthew A. Wilson's laboratory analyzed the CA1-specific NMDAR1 knockout mice by their multiple electrode recording technology applicable to freely moving rodents. They discovered that in these mutant mice, the coordinated activity of ensembles of CA1 neurons specific to the animal's locations (called place fields or place cells) is drastically impaired. These findings, when combined with the findings made in Tonegawa's laboratory (see above), constitute the first cohesive description of molecular, cellular, and neuron ensemble mechanisms for a specific cognitive function, namely spatial memory.
Dr. Earl K. Miller's laboratory made an important discovery regarding our ability to integrate the "what" and "where" information of objects. What and where are known to be processed separately in the visual system. Dr. Miller's laboratory identified prefrontal neurons that respond to both types of information of an object. These neurons may comprise a crucial link that allows actions to be directed toward objects.
Dr. William G. Quinn's laboratory has made substantial progress on two major projects - molecular cloning of the radish gene and development of a strong selection scheme for new learning mutants.
The radish mutation is crucial to the understanding of memory storage processes because it eliminates one of two forms of long-term memory -- consolidated or amnesia-resistant memory -- while sparing the other (protein-synthesis dependent memory). Dr. Quinn's laboratory has positionally mapped the radish gene to a 140-kb interval on the Drosophila X chromosome, and they have cloned the DNA in this interval. They are currently isolating and sequencing cDNAs corresponding to mRNA transcripts from this interval. The sequence of one transcript is intriguing -- it encodes an mRNA binding protein, possibly a splicing factor. Other sequenced transcripts have high homology to mouse mRNA, currently unknown of function.
Selecting learning and memory mutants is currently tedious and unreliable. It requires breeding and behavioral screening of groups of identical, mutagenized flies. However, Quinn's laboratory has selected new (clonable) alleles of one learning mutant based on partial suppression of the female sterile phenotype of another learning mutant, dunce. Aberrant cyclic AMP signaling in mutant dunce flies apparently affects both behavior and ability. The memory mutation amnesiac partially suppresses the female sterility of dunce, apparently by metabolic compensation. They are now engineering a more pronounced aberration in the cyclic AMP metabolic pathway to produce more severe female sterility for tighter selection screens. Initial engineering results on this project are very encouraging.
In Dr. Guosong Liu's laboratory, the overall research objective is to study how synaptic activities regulate the strength of interconnections between neurons in the central nervous system and what role activity plays in the process of synapse formation, elimination, and consolidation. Previously, they have studied the mechanism of synaptic transmission and synaptic plasticity in single synapses, as well as synapse formation and regulation during early development, using gene knockout animals and transfection in cultured neurons.
INTERACTION WITH OTHER DEPARTMENTS
Dr. Susumu Tonegawa and Dr. David Baltimore jointly organized a weekly informal discussion group among faculty members from the Department of Biology, the Department of Brain and Cognitive Sciences, and the Whitehead Institute who are interested in neurobiology and neuroscience. Ten to twenty faculty members joined each week and were engaged in very lively discussions on various topics in brain research.
Susumu Tonegawa
MIT Reports to the President 1996-97