Novel mechanisms regulating NMDAR-dependent synaptic plasticity: anion channels and presynaptic NMDARs

B_04_Hyungju Park(photo)
Hyungju Park
Korea Brain Research Institute

Abstract :

Presynaptic glutamate released by the certain type of neural activities can activate N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) in postsynaptic dendrites, leading to induction of long-term potentiation (LTP) at many excitatory synapses. However, recent studies have also suggested possible actions of glutamate released from astrocytes in regulating synaptic functions, but the exact mechanisms are remained to be elucidated. Furthermore, NMDARs expressed at presynaptic axons are also thought to be involved in the process of LTP formation, but how presynaptic NMDARs regulate LTP induction remains to be clarified.

Our recent studies provide key evidence for mechanisms of long-term synaptic plasticity regulated by astrocytic glutamate and presynaptic NMDARs. Our first study showed that glutamate could be released from hippocampal CA1 astrocytes through Ca2+-activated anion channel, Bestrophin 1 (Best1), and this Best1 channel-mediated astrocytic glutamate is able to elevate synaptic glutamate concentration, resulting in both GluN2A-containing NMDAR activation and NMDAR-dependent synaptic potentiation. These results suggest an additional mechanism for NMDAR-dependent synaptic plasticity mediated by astrocytic anion channel-dependent glutamate.

On the other hand, we also demonstrated that activation of presynaptic NMDARs at corticostriatal synapses by LTP-inducing stimuli can trigger activity-dependent secretion of brain-derived neurotrophic factor (BDNF), a member of a small family of secreted growth factor family protein. Both sustained axonal Ca2+ elevation and BDNF secretion were observed in response to the LTP-inducing stimuli, and these events were dependent on expression of functional NMDARs at presynaptic axons. These results demonstrate an equally important role of presynaptic NMDARs as that of postsynaptic NMDARs in LTP induction.



  • 2000~2007 Ph.D. (Biological Science/Neurobiology) Seoul National University, Seoul, Korea (advisor: Dr. Bong-Kiun Kaang)
  • 1996~2000 B.S. (Biological Science) Seoul National University, Seoul, Korea


Professional Activities

  • 2015-present Senior Researcher / Principal Investigator,Molecular Neurobiology Lab, Department of Structure & Function of Neural Networks, Korea Brain Research Institute (KBRI), Daegu, South Korea
  • 2015- present Adjunct Professor, Department of Brain & Cognitive Sciences, Daegu Gyeongbuk Institute of Science & Technology (DGIST), Daegu, South Korea
  • 2015-Present Reviewer for Molecular Brain
  • 2014-Present Reviewer for Developmental Neurobiology
  • 2013-2015 Regular member of Bay Area Korean-American Scientist in Biotech and Pharmaceutical (BAKAS)
  • 2012-2015 Associate Specialist (advisor: Dr. Mu-ming Poo), Department of Molecular & Cell Biology, UC Berkeley, Berkeley, CA, USA.
  • 2012 President, Korean Life Scientists in the bay area (KOLIS)
  • 2010-Present Reviewer for Journal of Physiology
  • 2009-2012 Postdoctoral fellow (advisor: Dr. Mu-ming Poo), Department of Molecular & Cell Biology, UC Berkeley, Berkeley, CA, USA.2007-2009 Postdoctoral fellow (advisor: Dr. C Justin Lee), Center for Neural science, Korea Institute of Science & Technology (KIST), Seoul, South Korea
  • 2004-Present Regular member of Society for Neuroscience


Awards & Honors

  • 2007-2009 STAR-Postdoctoral Fellowship(KIST, South Korea)
  • 2000-2005 Brain Korea 21 Research Fellowship(Korea Ministry of Education & Human Resources Development)