My laboratory focuses on the study of synaptic transmission in the mammalian central nervous system. Synapses are the sites at which electrical signals in presynaptic neurons are converted to chemical signals (neurotransmitter release), and the released neurotransmitter induces postsynaptic responses in the form of electrical and chemical signals (such as an increase in the intracellular Ca2+ concentration). The efficiency of this two-step information flow during synaptic transmission is important to the control of neural network activity. The long-term goal of our research is to understand how the efficiency of synaptic transmission is regulated, and how its disruption contributes to neurological and psychiatric disorders, such as brain ischemia, dystonia, post-traumatic stress disorder and autism.
We are currently focusing on two major aspects of synaptic transmission. In one project, we are analyzing fundamental parameters of neurotransmitter release: the amount of neurotransmitter loaded into synaptic vesicles, the likelihood of neurotransmitter release under particular conditions, and variability in the amount of released neurotransmitter. A second focus is on Ca2+ dynamics in postsynaptic neurons. In the dendrites of these neurons, the Ca2+ concentration rises locally and transiently in response to neurotransmitter, and the resulting highly concentrated Ca2+ can propagate as a wave along the dendrites toward the cell body. We are investigating the precise roles of such Ca2+ waves, as well as the mechanisms that underlie their generation and propagation.
Through these studies on both pre- and postsynaptic components of synaptic transmission, we expect to reveal the basic mechanisms of neural signaling, and the modes of their modulation under physiological and pathological conditions. For these studies, we are using live, cultured rodent neurons and astrocytes as a model system. This is a wonderful time for us, as fluorescence imaging, electrophysiological technology and electron microscopy are at stages where they can be combined in new ways, and used to look at processes at new, molecular levels of detail. Our studies should provide fresh insights into an old, but ever fascinating, field of research.
1. Harata NC, Choi S, Pyle JL, Aravanis AM, and Tsien RW. Frequency-dependent kinetics and prevalence of kiss-and-run and reuse at hippocampal synapses studied with novel quenching methods. Neuron 49: 243-256, 2006.
2. Harata NC, Aravanis AM, and Tsien RW. Kiss-and-run and full-collapse fusion as modes of exo-endocytosis in neurosecretion. J Neurochem 97: 1546-1570, 2006.
3. Harata NC, Ryan TA, Smith SJ, Buchanan J, and Tsien RW. Visualizing recycling synaptic vesicles in hippocampal neurons by FM 1- 43 photoconversion. Proc Natl Acad Sci U S A 98: 12748-12753, 2001
4. Harata NC, Pyle JL, Aravanis AM, Mozhayeva M, Kavalali ET, and Tsien RW. Limited numbers of recycling vesicles in small CNS nerve terminals: implications for neural signaling and vesicular cycling. Trends Neurosci 24: 637-643, 2001.