A transcriptional constraint mechanism limits the homeostatic response to activity deprivation in mammalian neocortex

Healthy neuronal networks rely on homeostatic plasticity to maintain stable firing rates despite changing synaptic drive. These mechanisms, however, can themselves be destabilizing if activated inappropriately or excessively. For example, prolonged activity deprivation can lead to rebound hyperactivity and seizures. While many forms of homeostasis have been described, whether and how the magnitude of homeostatic plasticity is constrained remains unknown. Here we uncover negative regulation of cortical network homeostasis by PAR bZIP family of transcription factors. In their absence the network response to prolonged activity withdrawal is too strong and this is driven by exaggerated upregulation of recurrent excitatory synaptic transmission. These data indicate that transcriptional activation is not only required for many forms of homeostatic plasticity but is also involved in restraint of the response to activity deprivation. ### Competing Interest Statement The authors have declared no competing interest.