Abstract
Activity-regulated genes sculpt neural circuits in response to sensory experience. These calcium-sensitive genes generally fall into two categories: transcription factors and proteins that function at synapses. Yet little is known about activity-regulated, cytosolic proteins that transduce signals between the neuronal membrane and the nucleus. Using the visual system as a model, we investigated the role of the activity-regulated, non-canonical Ras-like GTPase Rem2 in vivo . We demonstrate that Rem2 -/- mice fail to exhibit normal ocular dominance plasticity during the critical period. At the circuit level, cortical layer 2/3 neurons in Rem2 -/- mice show deficits in both postsynaptic scaling up of excitatory synapses and misregulation of intrinsic excitability. Further, we reveal that Rem2 plays a novel, cell-autonomous role in regulating neuronal intrinsic excitability. Thus, Rem2 is a critical regulator of neural circuit function and distinct homeostatic plasticity mechanisms in vivo . HIGHLIGHTS Rem2 is required in excitatory cortical neurons for normal ocular dominance plasticity Rem2 regulates postsynaptic homoeostatic synaptic scaling up Rem2 alters the intrinsic excitability of neurons in a cell-autonomous manner.