Astrocytes close a critical period of motor circuit plasticity

Abstract

AbstractCritical periods – brief intervals where neural circuits can be modified by sensory input – are necessary for proper neural circuit assembly. Extended critical periods are associated with neurodevelopmental disorders, including schizophrenia and autism; however, the mechanisms that ensure timely critical period closure remain unknown. Here, we define the extent of a critical period in the developing Drosophila motor circuit, and identify astrocytes as essential for proper critical period termination. During the critical period, decreased activity produces larger motor dendrites with fewer inhibitory inputs; conversely, increased motor neuron activity produces smaller motor dendrites with fewer excitatory inputs. Importantly, activity has little effect on dendrite morphology after critical period closure. Astrocytes invade the neuropil just prior to critical period closure, and astrocyte ablation prolongs the critical period. Finally, we use a genetic screen to identify astrocyte-motor neuron signaling pathways that close the critical period, including Neuroligin-Neurexin signaling. Reduced signaling destabilizes dendritic microtubules, increases dendrite dynamicity, and impairs locomotor behavior, underscoring the importance of critical period closure. Previous work defines astroglia as regulators of plasticity at individual synapses; here, we show that astrocytes also regulate large-scale structural plasticity to motor dendrite, and thus, circuit architecture to ensure proper locomotor behavior.