Cellular and Molecular Neurobiology, Vol. 19, No. 5, 1999 Synaptic Potentiation Induced by a Protein Factor in Cultured Cerebral Neurons Suguru N. Kudoh, 1 Kazuyuki Kiyosue, 1 Michiki Kasai, 2 and Takahisa Taguchi 1,3 Received April 27, 1998; accepted November 13, 1998 SUMMARY 1. We reported in a previous paper that long-lasting enhancement of spontaneous excitatory post synaptic currents (SEPSCs) in cultured chick cerebral neurons was induced by exposure to a conditioned medium (CM) prepared by Mg 2+ -free treatment of neurons. This suggested that the CM contained a diffusible factor(s) for the potentiation. 2. In this paper, the factor(s) was shown to be a protein(s) by heat and trypsin treatment of the CM. 3. The factor induced the potentiation within 5 min, but it was not required for maintenance of increased SEPSCs. 4. The factors in CM induced the potentiation without protein synthesis. 5. Protein synthesis at least in postsynaptic neurons, was indispensable to induce the potentiation by the Mg 2+ -free condition. KEY WORDS: cell culture; long-term potentiation; neuronal signaling. INTRODUCTION The brain performs important functions such as learning and memory by modulating synaptic activities in the neuronal network. Long-term potentiation (LTP) is the most thoroughly investigated phenomenon of activity-dependent synaptic plasticity. Although LTP is commonly induced by high-frequency stimuli (Bliss and Lomo, 1973) or pairing protocol (Gustafsson et al., 1987), it can also be induced by removal of Mg 2+ from the extracellular medium in an active neuronal circuit (Neuman et al., 1987). The removal of Mg 2+ permits an N-methyl-D-aspartate-type glutamate receptor (NMDA-R) to be activated at a weakly depolarized membrane potential. The high-frequency stimuli and pairing protocol can activate NMDAR by largely depolarizing the membrane potential to remove the Mg 2+ blocking channel in the 1 Department of Organic Materials, Osaka National Research Institute, 1-8-31, Midorigaoka, Ikeda 563- 8577, Japan. 2 Division of Biophysical Engineering, Faculty of Systems and Human Science, Osaka University Gradu- ate School of Engineering Science, Toyonaka 560-0043, Japan. 3 To whom correspondence should be addressed. Fax: (+81) 727-51-9628. e-mail: taguchi@onri.go.jp 575 0272-4340/99/1000-0575$16.00/0  1999 Plenum Publishing Corporation