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].


Purkinje Cell Parallel Fiber Climbing Fiber Cerebellar Purkinje Cell Cerebellar Purkinje Neuron 
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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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