Activity-Dependent Structural Plasticity of Perisynaptic Astrocytic Domains Promotes Excitatory Synapse Stability

Reactive oxygen species (ROS) have been extensively studied as damaging agents associated with ageing and neurodegenerative conditions. Their role in the nervous system under non-pathological conditions has remained poorly understood. Working with the Drosophila larval locomotor network, we show that in neurons ROS act as obligate signals required for neuronal activity-dependent structural plasticity, of both pre- and postsynaptic terminals. ROS signaling is also necessary for maintaining evoked synaptic transmission at the neuromuscular junction, and for activity-regulated homeostatic adjustment of motor network output, as measured by larval crawling behavior. We identified the highly conserved Parkinson’s disease-linked protein DJ-1β as a redox sensor in neurons where it regulates structural plasticity, in part via modulation of the PTEN-PI3Kinase pathway. This study provides a new conceptual framework of neuronal ROS as second messengers required for neuronal plasticity and for network tuning, whose dysregulation in the ageing brain and under neurodegenerative conditions may contribute to synaptic dysfunction.

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TrkB phosphorylation by Cdk5 is required for activity-dependent structural plasticity and spatial memory

Nature Neuroscience ◽

10.1038/nn.3237 ◽

2012 ◽

Vol 15 (11) ◽

pp. 1506-1515 ◽

Cited By ~ 96

Author(s):

Kwok-On Lai ◽

Alan S L Wong ◽

Man-Chun Cheung ◽

Pei Xu ◽

Zhuoyi Liang ◽

...

Keyword(s):

Spatial Memory ◽

Structural Plasticity ◽

Activity Dependent

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Activity dependent structural plasticity in neuromorphic systems

2017 IEEE Biomedical Circuits and Systems Conference (BioCAS) ◽

10.1109/biocas.2017.8325074 ◽

2017 ◽

Cited By ~ 1

Author(s):

Richard George ◽

Giacomo Indiveri ◽

Stefano Vassanelli

Keyword(s):

Structural Plasticity ◽

Neuromorphic Systems ◽

Activity Dependent

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Activity-dependent structural plasticity of Purkinje cell spines in cerebellar vermis and hemisphere

Brain Structure and Function ◽

10.1007/s00429-014-0833-6 ◽

2014 ◽

Vol 220 (5) ◽

pp. 2895-2904 ◽

Cited By ~ 10

Author(s):

P. De Bartolo ◽

F. Florenzano ◽

L. Burello ◽

F. Gelfo ◽

L. Petrosini

Keyword(s):

Purkinje Cell ◽

Structural Plasticity ◽

Cerebellar Vermis ◽

Activity Dependent

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Activity-dependent structural plasticity after aversive experiences in amygdala and auditory cortex pyramidal neurons

Neuroscience ◽

10.1016/j.neuroscience.2016.04.045 ◽

2016 ◽

Vol 328 ◽

pp. 157-164 ◽

Cited By ~ 9

Author(s):

Tina Gruene ◽

Katelyn Flick ◽

Sam Rendall ◽

Jin Hyung Cho ◽

Jesse Gray ◽

...

Keyword(s):

Auditory Cortex ◽

Pyramidal Neurons ◽

Structural Plasticity ◽

Activity Dependent

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Reactive Oxygen Species Regulate Activity-Dependent Neuronal Structural Plasticity in Drosophila

10.1101/081968 ◽

2016 ◽

Cited By ~ 1

Author(s):

Matthew C. W. Oswald ◽

Paul S. Brooks ◽

Maarten F. Zwart ◽

Amrita Mukherjee ◽

Ryan J. H. West ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Structural Changes ◽

Second Messengers ◽

Physiological Role ◽

Reactive Oxygen ◽

Structural Plasticity ◽

Activity Level ◽

Oxygen Species ◽

Network Output ◽

Activity Dependent

AbstractNeurons are inherently plastic, adjusting their structure, connectivity and excitability in response to changes in activity. How neurons sense changes in their activity level and then transduce these to structural changes remains to be fully elucidated. Working with the Drosophila larval locomotor network, we show that neurons use reactive oxygen species (ROS), metabolic byproducts, to monitor their activity. ROS signals are both necessary and sufficient for activity-dependent structural adjustments of both pre- and postsynaptic terminals and for network output, as measured by larval crawling behavior. We find the highly conserved Parkinson’s disease-linked protein DJ-1ß acts as a redox sensor in neurons where it regulates pre- and postsynaptic structural plasticity, in part via modulation of the PTEN-PI3Kinase pathway. Neuronal ROS thus play an important physiological role as second messengers required for neuronal and network tuning, whose dysregulation in the ageing brain and under neurodegenerative conditions may contribute to synaptic dysfunction.

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LRRTM3 regulates activity-dependent synchronization of synapse properties in topographically connected hippocampal neural circuits

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2110196119 ◽

2022 ◽

Vol 119 (3) ◽

pp. e2110196119

Author(s):

Jinhu Kim ◽

Dongseok Park ◽

Na-Young Seo ◽

Taek-Han Yoon ◽

Gyu Hyun Kim ◽

...

Keyword(s):

Neural Circuits ◽

Mossy Fiber ◽

Transmembrane Protein ◽

Long Term Potentiation ◽

Excitatory Synapse ◽

Granule Neurons ◽

Structural And Functional Properties ◽

Ca3 Neurons ◽

Activity Dependent ◽

Deficient Mice

Synaptic cell-adhesion molecules (CAMs) organize the architecture and properties of neural circuits. However, whether synaptic CAMs are involved in activity-dependent remodeling of specific neural circuits is incompletely understood. Leucine-rich repeat transmembrane protein 3 (LRRTM3) is required for the excitatory synapse development of hippocampal dentate gyrus (DG) granule neurons. Here, we report that Lrrtm3-deficient mice exhibit selective reductions in excitatory synapse density and synaptic strength in projections involving the medial entorhinal cortex (MEC) and DG granule neurons, accompanied by increased neurotransmitter release and decreased excitability of granule neurons. LRRTM3 deletion significantly reduced excitatory synaptic innervation of hippocampal mossy fibers (Mf) of DG granule neurons onto thorny excrescences in hippocampal CA3 neurons. Moreover, LRRTM3 loss in DG neurons significantly decreased mossy fiber long-term potentiation (Mf-LTP). Remarkably, silencing MEC–DG circuits protected against the decrease in the excitatory synaptic inputs onto DG and CA3 neurons, excitability of DG granule neurons, and Mf-LTP in Lrrtm3-deficient mice. These results suggest that LRRTM3 may be a critical factor in activity-dependent synchronization of the topography of MEC–DG–CA3 excitatory synaptic connections. Collectively, our data propose that LRRTM3 shapes the target-specific structural and functional properties of specific hippocampal circuits.

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