The brain has billions of neurons that receive, analyze, and store information about internal and external conditions, and are highly interconnected. To prevent either hyperexcitability (epilepsy) or hyopexcitability (catatonia) of brain circuits, neurons possess an array of “homeostatic” plasticity mechanisms that serve to stabilize average neuronal firing.
Synaptic scaling is one such form of homeostatic plasticity that acts like a synaptic thermostat, and allows neurons to turn up or down the gain of synaptic transmission to stabilize average activity. The signaling pathways that allow neurons to perform this neat trick are incompletely understood, and it has been controversial whether neurons do this in a cell-autonomous manner, or whether synaptic scaling is induced in response to release of soluble factors such as the pro-inflammatory cytokine TNFα.
A study published this week in Journal of Neuroscience by Brandeis postdoctoral fellow Celine Steinmetz and Professor Gina Turrigiano helps to resolve this controversy by showing that TNFα is not instructive for synaptic scaling, but instead is critical for maintaining synapses in a plastic state in which they are able to express synaptic scaling. This study suggests that glial cells serve a permissive role in maintaining synaptic plasticity through release of soluble factors such as TNFα, while neurons actively adjust their synaptic thermostat in response to cell-autonomous changes in their own activity.