Astrocytes close a critical period of motor circuit plasticity

Sarah D. Ackerman, Nelson A. Perez-Catalan, Marc R. Freeman, Chris Q. Doe

Preprint posted on 16 May 2020

Article now published in Nature at

Showstoppers: Astrocytes and the plastic brain

Selected by Sejal Davla


Brain development in animals, be it humans, cats, or flies, displays a temporal window of heightened synaptic plasticity called a critical period. The critical period is an early postnatal time where the development and maturation of neuronal circuits are heavily sculpted by the sensory cues in response to environmental changes. The timing of the critical period window is precise for individual circuits in brain regions and is crucial for distinct brain functions. Failure to maintain the proper timing of the plasticity window could lead to a range of synaptic and/or circuit-level changes as evident in neurodevelopmental disorders such as autism and schizophrenia1.

What starts and ends the critical period? Many cellular and functional processes such as the imbalance between excitation and inhibition are known to start the critical period. Similarly, closure of the critical period is remarkably shaped by structural changes such as thickening of the extracellular matrix and changes into neurotransmitter receptor types such as NMDA2. As neuronal circuits and synapses transform during the critical period, the neighboring astrocytes become crucial for the development, maintenance, and maturation of synapses. How astrocytes orchestrate plasticity changes during the critical period is vastly understudied.

Sarah Ackerman and colleagues in this preprint demonstrate a key astrocytic mechanism in the early Drosophila larval circuit that enables termination of the critical period.

Key Findings

Critical periods have been described in many contexts such as visual acuity, sound localization, and courtship song learning in a variety of species. The plastic phase lasts from hours to days depending on the circuit in question. The embryonic motor neuron circuit in Drosophila matures within a few hours before the larval hatching. This maturation phase, which first appears around 17 hours after egg laying, acts as a critical period to build a functional locomotion circuit. Disturbances in neuronal activity patterns during this period cause remarkable changes in the structure and function of the nervous system that alter behavior in the hatched larvae.

Structural plasticity – Make it or break it

One of the key mechanisms by which the activity influences circuit development during critical period is via adjustments in the morphology and branching pattern of a neuron’s dendrites. Using the clonal genetic methodology, the authors visualized the arborization pattern of individual motor neurons at a high resolution after changing intrinsic activity patterns using optogenetics or thermogenetic. The silencing of activity in motor neurons during the critical period leads to increased complexity in arborization whereas activation for as little as 15 min leads to a decrease in arborization. The authors elegantly correlate the duration of optogenetic stimulation with structural plasticity. Silencing is required for a longer duration since it leads to increased arborization which demands the synthesis and extension of the new membranes. In opposition, decreased arbor complexity that occurs after a rapid collapse of cytoskeletal machinery and membrane retraction can be achieved with a short stimulation protocol.

Excitatory/Inhibitory balance

It is well established that motor neurons in Drosophila employ homeostatic mechanisms to compensate for changes in synaptic excitation3. The authors first address how homeostatic compensation between excitatory and inhibitory processes in the circuit are linked to arborization changes in motor neurons. The increase in motor neuron activity reduced synaptic inputs from the excitatory cholinergic terminals whereas the reduction in intrinsic motor neuron activity decreases inhibitory GABAergic synapses onto motor neurons.

Astrocytes define the critical window

Astrocytes in Drosophila begin to infiltrate synaptic neuropil and contact synapses right after the onset of the critical period4. The critical period lasts for approximately 12 hours closing by 8 hours after larval hatching. Using live-imaging of the growth of motor neuron dendrites as a measure of synaptic plasticity, the authors report an extension of the critical period in animals where all astrocytes were ablated. Dendrites that normally turn less dynamic after the critical period retained the dynamic filopodia after astrocytic ablation.

What molecular mechanisms define the closure of a critical period? Ackerman and the team discovered several astrocytic molecules from a genetic screen important for the closure of critical period. Among many, the authors highlight neurexin-neuroligin signaling that is important for the timely closure of the critical period and normal locomotor behavior. Astrocyte-specific knockdown of neurologin extends the critical period in animals that show locomotor defects such as deviations in speed, distance, bending angle, with prolonged pauses. Neuroligins on astrocytes bind to its cognate ligand neurexin-1 present on motor neurons. This interaction stabilizes microtubules in motor neurons and confers them stability. The overexpression of neurexin-1 further enhances dendritic stability and leads to a precocious closure of the critical period.

Why this work is important?

The invertebrate nervous system which is often considered hard-wired is in fact plastic during development. While vertebrate visual and auditory circuits are well-established models to study critical period, there is no such model circuit in Drosophila. The authors here describe a model of critical plasticity that lasts only a short 12 hours with clear, visible hallmarks in structural changes and behavior. Coupled with the myriad advantages that Drosophila offers such as easy genetic manipulation, readily visible phenotypes, the availability of detailed connectome of this circuit, and the toolkit to visualize and manipulate individual cells, the authors uncovered new plasticity mechanisms of neuron-glia interaction during the critical period.

Questions for authors:

  1. When does the critical period end in animals that lack all astrocytes?
  2. What proportion of astrocytes needs to be ablated to extend the critical period? For example, will the ablation of a subset of astrocytes in a hemi-segment or a partial loss of astrocytic membranes in the neuropil is sufficient to change the timing of critical period?
  3. What happens to astrocytes’ size and its coverage of synaptic motor neuropil when motor neuron terminals are reduced or enhanced upon optogenetic activation?
  4. Do motor and sensory synaptic areas that normally tile with each other in a hemi-segment lose their target territories when astrocytes are ablated?


  1. Meredith, R.M. (2016). Critical periods and neurodevelopmental brain disorders. In Environmental Experience and Plasticity of the Developing Brain, A. Sale (Ed.).
  2. Sengpiel F. The critical period.Curr Biol. 2007 Sep 4;17(17):R742-3.
  3. Baines RA, Uhler JP, Thompson A, Sweeney ST, Bate M. Altered electrical properties in Drosophila neurons developing without synaptic transmission. J Neurosci. 2001;21(5):1523‐ doi:10.1523/JNEUROSCI.21-05-01523.2001
  4. Stork T, Sheehan A, Tasdemir-Yilmaz OE, Freeman MR. Neuron-glia interactions through the Heartless FGF receptor signaling pathway mediate morphogenesis of Drosophila astrocytes. Neuron. 2014;83(2):388‐ doi:10.1016/j.neuron.2014.06.026

Tags: astrocytes, critical period, drosophila, plasticity

Posted on: 9 June 2020


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