Tuning into diversity of homeostatic synaptic plasticity.

Neurons are endowed with the remarkable ability to integrate activity levels over time and tune their excitability such that action potential firing is maintained within a computationally optimal range. These feedback mechanisms, collectively referred to as "homeostatic plasticity", enable neurons to respond and adapt to prolonged alterations in neuronal activity by regulating several determinants of cellular excitability. Perhaps the best-characterized of these homeostatic responses involves the regulation of excitatory glutamatergic transmission. This homeostatic synaptic plasticity (HSP) operates bidirectionally, thus providing a means for neurons to tune cellular excitability in response to either elevations or reductions in net activity. The last decade has seen rapid growth in interest and efforts to understand the mechanistic underpinnings of HSP in part because of the theoretical stabilization that HSP confers to neural network function. Since the initial reports describing HSP in central neurons, innovations in experimental approaches have permitted the mechanistic dissection of this cellular adaptive response and, as a result, key advances have been made in our understanding of the cellular and molecular basis of HSP. Here, we review recent evidence that outline the presence of distinct forms of HSP at excitatory glutamatergic synapses which operate at different sub-cellular levels. We further present theoretical considerations on the potential computational roles afforded by local, synapse-specific homeostatic regulation. This article is part of the Special Issue entitled 'Homeostatic Synaptic Plasticity'.