Activity based checkpoints ensure circuit stability in the olfactory system

Olfactory circuits function at birth, yet are continuously remodeled through the integration of adult-born interneurons into the olfactory bulb in a manner that preserves olfactory perceptual stability throughout adult life. The mechanisms that ensure appropriate circuit stability in this dynamic context remain poorly understood. Since interneurons sculpt the excitatory output of mitral and tufted (MT) neurons to the olfactory cortex, we predicted that MT neurons might instruct interneuron wiring in the adult brain. By blocking synaptic transmission from MT neurons we show that MT neuronal activity is critical to maintain olfactory bulb integrity and interneuron survival. Blocking interneuron death uncovered a second activity-dependent checkpoint regulating dendrite branching. In contrast, cortical circuits and MT neurons remain stable in the face of these silent and degenerating olfactory circuits. These studies identify a circuit-specific role for non-sensory activity in regulating integration of neurons into the adult brain, as predicted by previous computational models.