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August 4, 2003
Neuroimaging at the MBL: Moving the Field Forward
Calcium Imaging Suggests Dendrite Plasticity
Woods Hole--The idea that changes in the strength in a synapse, or junction between nerve cells, underlies learning and memory is a cornerstone of modern neuroscience. Work related to 'synaptic plasticity' even won the Nobel Prize in Physiology or Medicine in 2000. "But that's clearly not the whole story," says Dr. Daniel Johnston, a summer researcher at the Marine Biological Laboratory in Woods Hole, Mass., and a member of the Laboratory's Neuroimaging Cluster, new this year. Based on work using a sophisticated research technique known as 'calcium imaging,' Johnston and colleagues believe that there may be a parallel and complementary plasticity within dendrites, the parts of neurons to first receive information from the synapses.
"We have found a lot of ion channels in the dendrites," says Johnston, "which no one thought were there." These channels appear to control the flow of sodium, potassium and calcium ions within the neurons. Increases in calcium concentrations inside the neuron lead to changes in synaptic strength. Molecules known to be important for learning and memory, such as cyclic AMP and protein kinases, also regulate these ion channels. Changes in the channels and the resulting flow of ions in dendrites may be as important to learning and memory as are changes at the synapses.
To investigate the dendrites, Johnston and fellow researchers inject dyes into individual living rat hippocampal neurons, and then illuminate the cell with light of a certain wavelength. The dyes, which bind available calcium ions, rapidly emit light of a different wavelength when the concentration of calcium ions increases inside the cell. Digital cameras and sensitive photodetectors record the emitted light hundreds of times per second, and allow researchers to see changes in calcium concentrations over very short periods of time and in very precise locations within the cell.
Johnston believes that his imaging work on the cellular mechanisms of neuroplasticity may also lead to a better understanding of neurological disorders such as aging and epilepsy as well as certain types of psychiatric and cognitive dysfunction. "We're just touching the tip of the iceberg of knowing how dendrites work in normal and abnormal brain activity," he says. "New methods in neuroimaging are what make these types of studies possible."
About the Neuroimaging Research Cluster at the MBL
The Neuroimaging Cluster at the Marine Biological Laboratory is a new collaboration of internationally distinguished researchers who image living tissues to understand basic mechanisms of nervous systems. Bringing together visiting summer investigators, the Cluster provides dedicated laboratory space and equipment and a critical but rare opportunity for sustained personal interaction between some of the best researchers and imagers in the world.
Research topics for members of the Cluster include recognition and remembrance of odors; calcium regulation of neurotransmitter release; signal integration in single vertebrate dendrites; basic mechanisms of neuronal communication; transmitter release in the squid giant synapse, and mechanisms of short-term memory.
The Laboratory's investment in the Cluster should yield dividends of better understanding of epilepsy and Alzheimer's Disease, as well as psychological diseases such as depression and schizophrenia. According to Dan Johnston, a professor of neuroscience at Baylor College of Medicine and one of the leaders of the new program, the Cluster provides an environment for scientists to not only collaborate on projects, but, perhaps more importantly, to transfer neuroimaging technology to other researchers. "You're not going to find a place anywhere else in the world with this concentration of expertise in neuroimaging," says Johnston. "The sharing of technical ideas will move this field forward."
One imaging method used in the cluster is the recently developed 2 Photon microscope. This microscope is the most powerful imaging tool available for looking at very small parts of single neurons embedded in brain tissue. It uses short pulses from an infrared laser to excite fluorescent molecules inside neurons. The neurons can be up to 1 mm below the surface, as infrared light penetrates brain tissue to a greater depth than does visible light. Light emitted by the fluorescent molecules creates images that allow researchers to follow the movement or changes in concentrations of important molecules or ions within or between neurons. The MBL has recently acquired a new 2 Photon microscope and installed it in the Cluster.
The current members of the cluster are George Augustine, Duke University Medical Center; Bob Baker, New York University School of Medicine; Larry Cohen, Yale University School of Medicine; Barbara Ehrlich, Yale University School of Medicine; David Glanzman, University of California Los Angeles; Dan Johnston, Baylor College of Medicine; Arthur Konnerth, Physiologisches Institut of the University of Saarlandes (Germany); Eileen Lafer, University of Texas; Matt Larkum, Max Planck Institute for Medical Research (Germany); Rodolfo Llinas, New York University School of Medicine; Jeff Magee, Lousiana State University; Bill Ross, New York Medical College; Mutsuyuki Sugimori, New York University Medical Center; David Tank, Princeton University, and Dejan Zecevic, Yale University School of Medicine.
The Marine Biological Laboratory is an internationally known, independent, nonprofit research and educational institution. It conducts the highest level of original research and education in biology, including the biomedical and environmental sciences. MBL hosts research programs in cell and developmental biology, ecosystems studies, molecular biology and evolution, neurobiology, behavior, global infectious diseases and sensory physiology. Its intensive graduate-level educational program is renowned throughout the life sciences. Founded in 1888, the MBL is the oldest private marine laboratory in the western hemisphere.