Two distinct mechanisms for experience-dependent homeostasis.

Abstract

Models of firing rate homeostasis such as synaptic scaling and the sliding synaptic plasticity modification threshold predict that decreasing neuronal activity (e.g. by sensory deprivation) will enhance synaptic function. Manipulations of cortical activity during two forms of visual deprivation (dark exposure (DE) and binocular lid suture (BS)) revealed that, contrary to expectations, spontaneous firing in conjunction with loss of visual input is necessary to lower the threshold for Hebbian plasticity and increases mEPSC amplitude. Blocking activation of GluN2B receptors, which are up-regulated by DE, also prevents the increase in mEPSC amplitude, suggesting that DE potentiates mEPSCs primarily through a Hebbian mechanism, not through synaptic scaling. Nevertheless, NMDAR-independent changes in mEPSC amplitude consistent with synaptic scaling could be induced by extreme reductions of activity. Therefore, two distinct mechanisms operate within different ranges of neuronal activity to homeostatically regulate synaptic strength.