The Journal of Neuroscience, September 1, 1999, 19(17):7326-7333
Entire Course and Distinct Phases of Day-Lasting Depression of
Miniature EPSC Amplitudes in Cultured Purkinje Neurons
Miho
Murashima1 and
Tomoo
Hirano1, 2
1 Department of Biophysics, Graduate School of Science,
Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan, and
2 Core Research for Evolutional Science and Technology,
Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, Japan
The cerebellar long-term depression (LTD) is the long-lasting
reduction of transmission efficacy at the granule neuron-Purkinje neuron (G-P) synapses and is a candidate mechanism for the motor learning. Despite extensive studies on its induction and expression mechanisms, it has not been known how long the LTD lasts. The LTD is
accompanied by the decrease in the postsynaptic responsiveness to
glutamate, the transmitter at G-P synapses. Therefore, during the LTD,
the amplitude of miniature EPSCs (mEPSCs) at G-P synapses should decrease. We studied the depression of mEPSC amplitudes (DME) as
a possible contributing factor for the LTD and found that the
conditioning treatment of cultured cerebellar neurons with 50 mM K+ and 100 µM
glutamate, an analogous condition used to induce the LTD, induced the
long-lasting DME. The mEPSC amplitudes recovered to the original level
48 hr after the 5 min conditioning treatment. Changing the duration of
the conditioning revealed that the DME consisted of two distinct
phases: the early phase lasting for a few hours and the late phase for
>1 d. The latter was distinguished from the former by its requirement
of prolonged conditioning treatment and syntheses of mRNA and protein
for the induction. There were critical periods for mRNA and protein
syntheses. The critical period for protein synthesis was much longer
than that for mRNA synthesis. These results demonstrate that the DME
lasts for 1-2 d and that it consists of two phases, whose induction
and maintenance mechanisms are distinct.
Key words:
synaptic plasticity; miniature EPSCs; culture; cerebellum; Purkinje neuron; long-term depression; late phase; critical
period; mRNA synthesis; protein synthesis
Copyright © 1999 Society for Neuroscience 0270-6474/99/19177326-08$05.00/0