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Research:
Synaptic circuits and experience-dependent plasticity
The vast capacity of the brain to process and store information arises from the large number of neurons and their synaptic connectivity. Research in my laboratory is motivated by general questions of how synapses operate and how they contribute to information processing and adaptation in circuits. While much of our past research has been in simple and accessible model systems in vitro, our current and future work centers on intact circuits in the rodent brain.
We continue to investigate mechanisms underlying activity-dependent synaptic plasticity in the rodent hippocampus, with an emphasis on inhibitory synapses. We are particularly interested in a phenomenon called homeostatic synaptic plasticity, which acts to compensate for chronic imbalances in neural activity. Our experiments aim to uncover rules and mechanisms by which persistent changes in activity alter different classes of inhibitory synapses.
The rodent olfactory brain (the olfactory bulb and piriform cortex) is now a target of significant effort in my lab. We develop and use novel optical and physiological methods in the living animal to seek answers to the following general questions:
- How is odor information represented in the early stages of the olfactory system?
- What is the logic of functional synaptic circuits in the early stages of the olfactory system?
- How is information processing affected by different brain states - sleep, wakefulness and neuromodulation?
- How are functional circuits in the olfactory system regulated by odor experience?
Selected Publications:
Olfaction
Tyler WJ, Petzold GC, Pal SK and Murthy VN. 2007. Experience-dependent modification of primary sensory synapses in the mammalian olfactory bulb. J. Neurosci. (in press).
Dietz SB and Murthy VN 2005. Contrasting short-term plasticity at two sides of the mitral-granule cell reciprocal synapse in mammalian olfactory bulb. J. Physiol. 569:475-488.
Synaptic Plasticity
Hartman KN*, Pal SK*, Burrone J and Murthy VN. 2006. Activity-dependent regulation of inhibitory synaptic transmission in hippocampal neurons. Nature Neuroscience. 9:642-649. * - equal contributors.
Samuel ADT, Silva RA and Murthy VN. 2003. Synaptic activity of the AFD neuron in Caenorhabditis elegans correlates with thermotactic long-term memory. J. Neurosci. 23:373-376.
Burrone J, O'Byrne M and Murthy VN. 2002. Multiple forms of synaptic plasticity triggered by selective suppression of activity in single neurons. Nature 420:414-418
Star EN, Kwiatkowski DJ. and Murthy VN. 2002. Rapid turnover of actin in dendritic spines and its regulation by activity. Nature Neuroscience, 5:239-246.
Murthy VN, Schikorski T, Stevens CF & Zhu, Y. 2001. Inactivity produces increase in transmitter release and synapse size. Neuron 32:673-682.
Cell Biology of the Synapse
Newton AJ, Kirchhausen T. and Murthy VN. 2006. Inhibition of dynamin completely blocks compensatory synaptic vesicle endocytosis. Proc. Natl. Acad. Sci. USA. 103:17955-17960.
Star EN, Newton, AJ and Murthy VN. 2005. Real-time imaging of Rab3a and Rab5a reveals differential roles in presynaptic function. J. Physiol. 569:103-117.
Li Z, Burrone J, Tyler WJ, Hartman KN, Albeanu DF and Murthy VN. 2005. Synaptic vesicle recycling studied using transgenic mice expressing synaptopHluorin. Proc. Natl. Acad. Sci. USA. 102:6131-6136.
Dertinger SKW, Jiang X, Li Z, Murthy VN and Whitesides GW. 2002. Gradients of substrate-bound laminin orient axonal specification of neurons. Proc. Natl. Acad. Sci. USA. 99:12542-12547.
Li Z and Murthy VN. 2001. Visualizing post-endocytic traffic of synaptic vesicles at hippocampal synapses. Neuron 31:593-605.
Reviews and Technical Papers
Burrone J*, Li Z* and Murthy VN. 2006. Studying vesicle recycling in presynaptic terminals using the genetically-encoded probe synaptopHluorin. Nature Protocols 1:2970-2978. * - equal contributors
Tyler WJ and Murthy VN. 2004. Synaptic vesicles. Curr. Biol. 14:R294-R297.
Burrone J and Murthy, VN. 2003. Synaptic gain control and homeostasis. Curr. Opin. Neurobiol. 13:560-567.
Murthy VN and De Camilli P. 2003. Cell biology of the presynaptic terminal. Ann. Rev. Neurosci. 26:701-728.
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