ArticleCerebral cortex (New York, N.Y. : 1991)2014
DOC2B and Munc13-1 differentially regulate neuronal network activity.
Article in Cerebral cortex (New York, N.Y. : 1991), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Schizophrenia is associated with altered DNA methylation variance.Molecular psychiatry · 2025Pooled it
- Biochemical and neurophysiological effects of deficiency of the mitochondrial import protein TIMM50.eLife · 2024Article
- Compromised transcription-mRNA export factor THOC2 causes R-loop accumulation, DNA damage and adverse neurodevelopment.Nature communications · 2024Article
- Brain-Targeted Liposomes Loaded with Monoclonal Antibodies Reduce Alpha-Synuclein Aggregation and Improve Behavioral Symptoms in Parkinson's Disease.Advanced materials (Deerfield Beach, Fla.) · 2023Article
- Article
- Linking α-synuclein-induced synaptopathy and neural network dysfunction in early Parkinson's disease.Brain communications · 2022Review
- Disrupted Excitatory Synaptic Contacts and Altered Neuronal Network Activity Underpins the Neurological Phenotype in PCDH19-Clustering Epilepsy (PCDH19-CE).Molecular neurobiology · 2021Article
- Phosphatidylinositol (4, 5)-bisphosphate targets double C2 domain protein B to the plasma membrane.Traffic (Copenhagen, Denmark) · 2017Article
- Shaping Neuronal Network Activity by Presynaptic Mechanisms.PLoS computational biology · 2015Article
- Munc13-1 Translocates to the Plasma Membrane in a Doc2B- and Calcium-Dependent Manner.Frontiers in endocrinology · 2013Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Alterations in the levels of synaptic proteins affect synaptic transmission and synaptic plasticity. However, the precise effects on neuronal network activity are still enigmatic. Here, we utilized microelectrode array (MEA) to elucidate how manipulation of the presynaptic release process affects the activity of neuronal networks. By combining pharmacological tools and genetic manipulation of synaptic proteins, we show that overexpression of DOC2B and Munc13-1, proteins known to promote vesicular maturation and release, elicits opposite effects on the activity of the neuronal network. Although both cause an increase in the overall number of spikes, the distribution of spikes is different. While DOC2B enhances, Munc13-1 reduces the firing rate within bursts of spikes throughout the network; however, Munc13-1 increases the rate of network bursts. DOC2B's effects were mimicked by Strontium that elevates asynchronous release but not by a DOC2B mutant that enhances spontaneous release rate. This suggests for the first time that increased asynchronous release on the single-neuron level promotes bursting activity in the network level. This innovative study demonstrates the complementary role of the network level in explaining the physiological relevance of the cellular activity of presynaptic proteins and the transformation of synaptic release manipulation from the neuron to the network level.
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