Arc function in homeostatic plasticity
LTP and LTD are self-reinforcing mechanisms and might push synaptic strength to one extreme or another if left unchecked. This can reduce the capacity of the system to respond to additional changes in activity and might also make the network unstable, leading to conditions such as epilepsy. To prevent such extremes, a neuron responds to long-term increases or decreases in activity by scaling its response to activity down or up, respectively, to maintain the same average firing rate. This cell-wide form of plasticity, termed homeostatic scaling, is highly sensitive to levels of Arc. Normal scaling responses to manipulations of neuronal activity in vitro are lost in Arc KO neurons, as well as in neurons overexpressing Arc [65]. Arc is also necessary for a more synapse-specific form of homeostasis, in which the strength of a synapse is increased in response to a reduction in the firing rate of the presynaptic neuron [66].