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Systems Biology Meets Single-Cell Physiology: Role of a Positive-Feedback Signal Transduction Network in Cerebellar Long-Term Synaptic Depression

  • Keiko Tanaka
  • George J. Augustine

It is widely assumed that persistent changes in the brain, such as those occurring during learning, memory, development, and various pathological conditions, are mediated by long-lasting, plastic changes in synaptic efficacy [1]. Long-term depression (LTD) of excitatory transmission at cerebellar Purkinje cells is an attractive system for studies of such long-lasting synaptic plasticity [2]. LTD arises from interaction of the two excitatory synaptic inputs that innervate Purkinje cells: climbing fibers (CF) and parallel fibers (PF). Simultaneous activation of these inputs causes a LTD of the efficacy of PF synapses [2].

The signals generated by the activity of these synapses are well understood. CF activation depolarizes the Purkinje cell and produces a rise in the intracellular Ca2+ This rise in [Ca2+]i is necessary and sufficient to account for the CF contribution to LTD [3–5]. PF synapses produce several signals that are important for LTD. PF activity produces two messengers within Purkinje cells: diacylglycerol (DAG) and inositol trisphosphate (IP3). DAG is important for LTD induction, via its well-known ability to activate protein kinase C (PKC) [6–8], while IP3 contributes to LTD signaling by releasing Ca2+ from intracellular stores and thereby elevating [Ca2+]i [9–12]. PF activity also appears to activate nitric oxide synthase in the presynaptic terminals of PFs, generating the membrane-permeant gas, nitric oxide (NO), that is also involved in LTD [13–17].

Keywords

Purkinje Cell Parallel Fiber Climbing Fiber Cerebellar Purkinje Cell Cerebellar Purkinje Neuron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer 2009

Authors and Affiliations

  • Keiko Tanaka
    • 1
    • 2
  • George J. Augustine
    • 3
  1. 1.Department of Biophysics and Biochemistry, Graduate School of ScienceUniversity of TokyoTokyoJapan
  2. 2.PRESTO, Japan Science and Technology AgencyTokyoJapan
  3. 3.Department of NeurobiologyDuke Medical CenterDurhamUSA

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