Dr. Kristen M. Harris, chief of the Synapses and Cell Signaling Program at the Medical College of Georgia, has received the National Institute of Neurological Disorders and Stroke's Javits Neuroscience Investigator Award for her studies of anatomical changes that occur at synapses, the sites of communication between brain cells.
Congress established the Senator Jacob Javits Award in the Neurosciences in 1983 to honor the late New York senator with amyotrophic lateral sclerosis who was an advocate for research of the brain and nervous system. Nearly 480 awards have been made to date.
The award recognizes investigators who have made substantial contributions to the neurological science field and likely will continue being highly productive for the seven-year term of award funding.
Dr. Harris, Georgia Research Alliance Eminent Scholar in Synapses and Cell Signaling, was nominated for the award by Dr. Yuan Liu, program director in Channels, Synapses and Circuits; Technology Development at the National Institute of Neurological Disorders and Stroke of the National Institutes of Health. She was selected by the National Advisory Neurological Disorders and Stroke Council.
A total dollar amount has not yet been determined for the funding, which will support studies to document in living animals the changes in synapses that likely enable learning and memory. However, Dr. Harris requested nearly $1.4 million over the original five-year period.
"This is a terrific honor for Dr. Harris and for the university," said Dr. David M. Stern, dean of the MCG School of Medicine. "In her near 30-year career, Dr. Harris and her team have made fundamental discoveries about anatomic changes in synapses that likely will not only help us better understand how we learn and remember but also pave the way for better treatments of diseases that disrupt these processes. Her latest grant helps take critical forward steps, from studying slices of brain tissue to intact, living models."
Dr. Harris' studies focus on synapses where brain cells share chemical messengers called neurotransmitters and how these synapses change in size and number so information can be learned and remembered.
"There have been a lot of people working hard together to develop the tools to investigate at the submicron level how the structure of the brain changes; we have to look at the submicron level because that is the size of synapses," says Dr. Harris who came to MCG in 2002 from Boston University. She has assembled a team at MCG that includes Dr. Bitao Shi, research assistant professor of neuroinformatics; Dr. Jennifer Bourne, postdoctoral fellow in neuroscience; Robert Smith and Elizabeth Perry, electron microscopists; Jim Parkerson, Mark Witcher and Anusha Mishra, who contribute to various aspects of the project; and Wendy Cline Paschal, research project coordinator.
At this submicron level, she focuses on how synapses change in response to stimulation, a process called long-term potentiation, which scientists believe is a basic mechanism for learning and memory. They also believe long-term potentiation, or LTP, can be a model for studying whether experimental treatments have affected the brain. "You can apply a drug or manipulate genes in study animals, then look and see whether it was involved in the cellular mechanisms of learning," Dr. Harris says. "If it was, then you would take the same animal and test it to see if it learns as well as its litter mates."
She uses three-dimensional images of synapses, where the threadlike extensions called axons of one neuron meet up with branch-like structures called dendrites of the next to learn more about changes at this critical juncture. Most excitatory synapses occur at tiny thorn-like protrusions from the dendrites called dendritic spines.
LTP requires new protein synthesis that enables consolidation and preservation of changes at the synapse; after LTP, dendritic spines undergoing protein synthesis increases from 10 percent to 40 percent. "This also is a new area of understanding in the brain. You don't have to go down to the nucleus to initiate new protein synthesis," Dr. Harris says. "We are finding that it can be induced and it can be targeted very specifically to a subset of the spines that have undergone LTP." In fact, when protein synthesis is blocked, 'long-term' potentiation does not last.
She isn't sure that the changes she is finding enable learning and memory in humans. "That is two steps beyond this grant," says Dr. Harris, who already is working with MCG colleagues to apply for an NIH Program Project grant that may take at least one of those steps. "Right now, we only know that it would explain the amount of LTP that we get in the cell."
The Javits Award will enable study of the cellular mechanisms of learning and short-term memory in living laboratory animals to see whether what they have found in brain slices translates to an intact animal brain. "We are going to work across a timeframe, after induction of long-term potentiation, and find out when the different molecules change, whether the synapses remain enlarged, start to fall off, fall off with LTP or something else."
Dr. Cliff Abraham, neuroscientist and chief of the Psychology Department at the University of Otago in Dunedin, New Zealand, who is known for his electrophysiology studies of LTP in the intact brain, will work with Dr. Harris on the grant.
As she was putting that grant application to bed, Dr. Harris remembers thinking reviewers might consider it too much ground to cover in the five years she originally requested. Instead, the application was given a high score by reviewers and subsequently nominated for the seven-year Javits Award. "I was really happy that they thought Javits instead of over-ambitious," Dr. Harris says.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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