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The Journal of Neuroscience, 2001, 21:RC170:1-6

RAPID COMMUNICATION
Postsynaptic Depolarization Scales Quantal Amplitude in Cortical Pyramidal Neurons

Kenneth R. Leslie, Sacha B. Nelson, and Gina G. Turrigiano

Department of Biology and Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454

Pyramidal neurons scale the strength of all of their excitatory synapses up or down in response to long-term changes in activity, and in the direction needed to stabilize firing rates. This form of homeostatic plasticity is likely to play an important role in stabilizing firing rates during learning and developmental plasticity, but the signals that translate a change in activity into global changes in synaptic strength are poorly understood. Some but not all of the effects of long-lasting changes in activity on synaptic strengths can be accounted for by activity-dependent release of the neurotrophin brain-derived neurotrophic factor (BDNF). Other candidate activity signals include changes in glutamate receptor (GluR) activation, changes in firing rate, or changes in the average level of postsynaptic depolarization. Here we combined elevated KCl (3-12 mM) with ionotropic receptor blockade to dissociate postsynaptic depolarization from receptor activation. Chronic (48 hr) depolarization, ranging between 62 and 36 mV, parametrically reduced the quantal amplitude of excitatory synapses in a BDNF-independent manner. This effect of depolarization did not depend on AMPA, NMDA, or GABA_A receptor signaling, action-potential generation, or metabotropic GluR activation. Together with previous work, these data suggest that there are two independent signals that regulate activity-dependent synaptic scaling in pyramidal neurons: low levels of BDNF cause excitatory synapses to scale up in strength, whereas depolarization causes excitatory synapses to scale down in strength.

Key words: BDNF; synaptic scaling; activity-dependent; synaptic plasticity; KCl; depolarization; mEPSC

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Copyright © Society for Neuroscience  0270-6474//$05.00/0

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