Input-specific homeostatic regulation of AMPA receptor accumulation at central synapses

Neurons are able to restore their activity to a set-point level when challenged by external or internal perturbations. This type of homeostatic plasticity is important in the maintenance of neuronal or network stability during development and normal brain function. One of the major cellular events underlying the expression of homeostatic regulation is the alteration of glutamatergic AMPA receptor (AMPAR) accumulation and thus, synaptic strength. Traditional global homeostatic plasticity is believed to adjust the input strength of all synapses. Since each individual synapse receives different input with varied levels of activity and distinct history of synaptic plasticity, an input-specific homeostatic regulation is necessary to restrain synaptic activity within a physiological range. Our studies suggest that at the single synapse level, homeostatic plasticity is expressed via input-specific alterations of AMPAR amounts. This homosynaptic homeostatic regulation is expected to play an important role in preventing the deleterious situations imposed by Hebbian plasticity to secure long-term synaptic stability.