MAR 19, 2014 09:00 AM PDT

Age-Dependent Responses of Dendrite Structure to Hippocampal Synaptic Plasticity

Presented At Neuroscience
  • Associate Chair, Department of Neuroscience, Professor of Neuroscience , Fellow Center for Learning and Memory, University of Texas at Austin
      Dr. Harris's goal is to elucidate the structural components involved in the cell biology of learning and memory. She has quantified the basic ultrastructure of synapses in several brain regions using reconstruction from serial section transmission electron microscopy (ssTEM). Her focus has been on dendritic spines because they are the major postsynaptic targets of excitatory axons throughout the brain and because their structure and composition serve both synaptic plasticity and stabilizing homeostatic mechanisms. She has developed and maintains an NIH-supported educational website on the ultrastructure of synapses. Dr. Kristen Harris received her PhD in Neuroscience in 1982 from the Northeastern Ohio Universities College of Medicine in Rootstown Ohio with Dr. Timothy Teyler, when she established postnatal day 15 as the earliest age to express enduring long-term potentiation. In 1984 she completed postdoctoral research in serial section transmission electron microscopy with Dr. Dennis Landis at Harvard Medical School and Dr. John Stevens at the University of Toronto. She then became a member of the faculty in Neurology at the Harvard Medical School and Children's Hospital, Boston where she remained until 1999. In 1999 she moved as tenured full professor to Boston University where she helped to establish an inter-departmental Program in Neuroscience. In 2002 she became a Georgia Research Alliance Eminent Scholar at the Medical College of Georgia where she established the Synapses and Cognitive Neuroscience Center and initiated the Human Brain Laboratory and recruited Dr. Sergei Kirov as its director. In 2006, she was recruited to the new Center for Learning and Memory at the University of Austin at Texas where she is currently Professor in Neurobiology.


    Dendritic spine shape enables sequestering of subcellular components needed for synaptic plasticity, including polyribosomes for local protein synthesis, smooth endoplasmic reticulum (SER) to regulate calcium and glutamate receptor trafficking, endosomes for redistribution of proteins and membrane, and the Golgi-like spine apparatus. In hippocampus and elsewhere, synapse size correlates with presynaptic vesicle numbers, which are greater in the presence of sparsely distributed mitochondria and perisynaptic astroglial processes. Diversity in composition signifies synapse-specific structural plasticity. Long-term potentiation (LTP) is a cellular model of learning well-suited to the investigation of structural synaptic plasticity. Hippocampal LTP in the rat has an abrupt onset at postnatal day 12 (P12) that is associated with the first occurrence of dendritic spines. In mature hippocampus, LTP results in loss of small dendritic spines with compensatory enlargement of remaining spine synapses, leading to a balanced sum total of synaptic surface area per dendritic segment (i.e. structural synaptic scaling). This structural scaling occurs as presynaptic vesicles are recruited to vesicle free zones, with pre-existing postsynaptic densities at the edges of synapses, thereby enlarging the synaptic active zone of potentiated synapses. A similar form of scaling occurs in the mature dentate gyrus in vivo, where dendritic spines and synapses enlarge with LTP in the middle molecular layer, but shrink in the inner and outer molecular layers that have concurrent long-term depression. At P15, LTP results in more dendritic spines without compensatory scaling in synapse size. Polyribosomes show differential dynamics at both young and mature ages depending on whether LTP was induced by tetanic or theta-burst stimulation. At P15, endosomes are rapidly recruited to enlarge spines. At immature and adult ages, the dendritic shaft contains SER that forms bridges where glutamate receptor trafficking is slowed in regions of high spine density. The SER becomes more tubular during LTP, a configuration that facilitates glutamate receptor trafficking. At both immature and adult ages, presynaptic vesicle counts are reduced with LTP, a phenomenon related to the presence of presynaptic recycling endosomes and mitochondria. In contrast to LTP, the response of mature dendrites to blocked synaptic transmission involves proliferation of spines, which does not occur on immature dendrites until after postnatal day 21. Thus, hippocampal synapses have unequal and sometimes opposite responses to plasticity-inducing activity depending on age and paradigm.

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