Neuronal networks are capable of undergoing rapid structural and functional changes called plasticity, which are essential for shaping circuit function during nervous system development. These changes range from short-term modifications on the order of milliseconds, to long-term rearrangement of neural architecture that could last for the lifetime of the organism. Neural plasticity is most prominent during development, yet also plays a critical role during memory formation, behavior, and disease. Therefore, it is essential to define and characterize the mechanisms underlying the onset, duration, and form of plasticity. Astrocytes, the most numerous glial cell type in the human nervous system, are integral elements of synapses and are components of a glial network that can coordinate neural activity at a circuit-wide level. Moreover, their arrival to the CNS during late embryogenesis correlates to the onset of sensory-evoked activity, making them an interesting target for circuit plasticity studies. Technological advancements in the last decade have uncovered astrocytes as prominent regulators of circuit assembly and function. Here, we provide a brief historical perspective on our understanding of astrocytes in the nervous system, and review the latest advances on the role of astroglia in regulating circuit plasticity and function during nervous system development and homeostasis.
Critical 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..
22Critical periods -brief intervals where neural circuits can be modified by sensory input -are 23 necessary for proper neural circuit assembly. Extended critical periods are associated with 24 neurodevelopmental disorders, including schizophrenia and autism; however, the mechanisms 25 that ensure timely critical period closure remain unknown. Here, we define the extent of a 26 critical period in the developing Drosophila motor circuit, and identify astrocytes as essential 27 for proper critical period termination. During the critical period, decreased activity produces 28 larger motor dendrites with fewer inhibitory inputs; conversely, increased motor neuron 29 activity produces smaller motor dendrites with fewer excitatory inputs. Importantly, activity 30 has little effect on dendrite morphology after critical period closure. Astrocytes invade the 31 neuropil just prior to critical period closure, and astrocyte ablation prolongs the critical period. 32Finally, we use a genetic screen to identify astrocyte-motor neuron signaling pathways that 33 close the critical period, including Neuroligin-Neurexin signaling. Reduced signaling 34 destabilizes dendritic microtubules, increases dendrite dynamicity, and impairs locomotor 35 behavior, underscoring the importance of critical period closure. Previous work defines 36 astroglia as regulators of plasticity at individual synapses; here, we show that astrocytes also 37 regulate large-scale structural plasticity to motor dendrite, and thus, circuit architecture to 38 ensure proper locomotor behavior. 39 40 41 2 Main 42 43 Critical periods are brief windows where neural circuit activity can modify the morphological 44 properties of neurons 1,2 . Critical periods integrate two opposing forces of plasticity to modify 45 neural circuits. Hebbian plasticity alters the function of individual synapses 3 , whereas 46 homeostatic plasticity encompasses changes to synaptic number, structure (homeostatic 47 structural plasticity), and function (homeostatic synaptic plasticity) across an entire neuron, as 48 well changes to local and long-range connectivity 1 . While homeostatic plasticity can occur in 49 some areas of the adult brain, dramatic activity-dependent remodeling is largely restricted to 50 early development 3-6 . Indeed, failure to terminate critical period plasticity is linked to a 51 number of neurodevelopmental and neuropsychiatric disorders, such as autism and 52 schizophrenia 2,7-10 . Although critical period closure must be tightly regulated, the molecular 53 mechanisms involved are poorly understood.54 55 A critical period of motor circuit plasticity 56 57To investigate critical period closure, we focused on two well-characterized Drosophila motor 58 neurons (MNs), aCC and RP2 11,12 . These MNs are segmentally repeated in the embryonic and 59 larval CNS (Fig. 1a), and are susceptible to activity-induced remodeling, but these pioneering 60 studies used chronic activity manipulations and did not define an end-point for homeostatic 61 plasticity 12-15 . Here, we expr...
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