Postsynaptic depolarization scales quantal amplitude in cortical pyramidalneurons

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 l ikely to play an important role in stabilizing firing rates during learning and developmental plasticity, but the signals that translate a change in a ctivity into global changes in synaptic strength are poorly understood. Som e but not all of the effects of long-lasting changes in activity on synapti c strengths can be accounted for by activity-dependent release of the neuro trophin 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 depolarizatio n. Here we combined elevated KCl (3-12 mM) with ionotropic receptor blockad e to dissociate postsynaptic depolarization from receptor activation. Chron ic (48 hr) depolarization, ranging between -62 and -36 mV, parametrically r educed the quantal amplitude of excitatory synapses in a BDNF-independent m anner. This effect of depolarization did not depend on AMPA, NMDA, or GABA( A) receptor signaling, action-potential generation, or metabotropic GluR ac tivation. Together with previous work, these data suggest that there are tw o 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 do wn in strength.