Most people probably take it for granted that our brains rarely experience extreme activity conditions such as epilepsy (hyperactivity) or catatonia (hypoactivity). But to neuroscientists this stability is quite puzzling, because our brain activity is constantly perturbed by both changes in the external world and by internal changes that result from learning and development. Over the past two decades, research pioneered by Brandeis neuroscientists has suggested that our brains solve this stability problem by using a set of “homeostatic” plasticity mechanisms that stabilize neural excitability. One of the best documented such mechanisms is known as homeostatic synaptic scaling, in which synaptic strengths are up- or down-regulated to compensate for external fluctuations in drive. This form of plasticity acts like a “synaptic thermostat” to maintain neural excitability within an optimal operational range. However, the molecular mechanisms by which changes in activity lead to bidirectional adjustments in synaptic strength are not fully understood. Now a recent paper published in the Journal of Neuroscience by Brandeis graduate student Qian Sun (PhD ’11) and Professor Gina Turrigiano shows that two abundant and well-studied synaptic proteins, PSD-95 and PSD-93 (or Postsynaptic Density-95 and 93), are critical for the expression of synaptic scaling.

PSD-95/PSD-93 are rock stars of the synaptic world. They are important synaptic proteins that act as “scaffolds” to organize other synaptic proteins, and are known to contribute to several non-homeostatic forms of synaptic plasticity such as long term potentiation and long term depression. This new study adds an additional critical function to the already complex role that the PSD-95 protein family plays in synaptic plasticity, by showing that PSD-95 mediates both scaling up and scaling down, but that these two directions of plasticity are mediated by distinct aspects of PSD-95 function. Taken together with other work, this study suggests that PSD-95/PSD-93 serve as critical synaptic organizers ~ synaptic conductors, if you will ~ that can mediate many forms of synaptic plasticity through distinct protein-protein interactions within the synapse. This study provides a glimpse into the complexity of the synaptic machinery, and sheds important new light into the mechanisms of homeostatic synaptic scaling.