Data for Cell Reports manuscript (Jan 2025)

Neocortical circuits maintain network stability through homeostatic plasticity mechanisms that use negative feedback to adjust excitation/inhibition balance, but how various forms of homeostatic plasticity operate <i>in vivo</i> is not well-understood. To examine whether excitatory synaptic scaling and intrinsic homeostatic plasticity (IHP) are engaged in a hierarchical or modular manner, we perturbed different aspects of neocortical circuit activity both <i>in vitro</i> and <i>in vivo</i>, and found that synaptic scaling and IHP are independently induced by sensing altered spiking and NMDA receptor (NMDAR) signaling, respectively. Despite this initial separation, their expression mechanisms bear similarities in time course, requirement of tumor necrosis alpha (TNFa) signaling, and ion channel trafficking pathways. Sensory experiences that affect NMDAR but not spiking activity selectively trigger IHP in visual cortex without recruiting synaptic scaling, supporting a modular model where synaptic and intrinsic mechanisms serve distinct functions.