ArticleJournal of neurophysiology2016
Network burst activity in hippocampal neuronal cultures: the role of synaptic and intrinsic currents.
Article in Journal of neurophysiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 91 citations in OpenAlex.
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- A human in vitro neuronal model for studying homeostatic plasticity at the network level.Stem cell reports · 2023Article
- Using Human-Induced Pluripotent Stem Cell Derived Neurons on Microelectrode Arrays to Model Neurological Disease: A Review.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Human-Derived Cortical Neurospheroids Coupled to Passive, High-Density and 3D MEAs: A Valid Platform for Functional Tests.Bioengineering (Basel, Switzerland) · 2023Article
- Third-order motifs are sufficient to fully and uniquely characterize spatiotemporal neural network activity.Scientific reports · 2023Article
- Selective inhibition of excitatory synaptic transmission alters the emergent bursting dynamics ofFrontiers in neural circuits · 2023Article
- Establishment of Neurotoxicity Assessment Using Microelectrode Array (MEA) with hiPSC-Derived Neurons and Evaluation of New Psychoactive Substances (NPS).International journal of stem cells · 2022Article
- Evaluating spatial and network properties of NMDA-dependent neuronal connectivity in mixed cortical cultures.Brain research · 2022Article
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Authors and funding
8 authors at 1 institution in 1 country.
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Abstract
The goal of this work was to define the contributions of intrinsic and synaptic mechanisms toward spontaneous network-wide bursting activity, observed in dissociated rat hippocampal cell cultures. This network behavior is typically characterized by short-duration bursts, separated by order of magnitude longer interburst intervals. We hypothesize that while short-timescale synaptic processes modulate spectro-temporal intraburst properties and network-wide burst propagation, much longer timescales of intrinsic membrane properties such as persistent sodium (Nap) currents govern burst onset during interburst intervals. To test this, we used synaptic receptor antagonists picrotoxin, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonate (CPP) to selectively block GABAA, AMPA, and NMDA receptors and riluzole to selectively block Nap channels. We systematically compared intracellular activity (recorded with patch clamp) and network activity (recorded with multielectrode arrays) in eight different synaptic connectivity conditions: GABAA + NMDA + AMPA, NMDA + AMPA, GABAA + AMPA, GABAA + NMDA, AMPA, NMDA, GABAA, and all receptors blocked. Furthermore, we used mixed-effects modeling to quantify the aforementioned independent and interactive synaptic receptor contributions toward spectro-temporal burst properties including intraburst spike rate, burst activity index, burst duration, power in the local field potential, network connectivity, and transmission delays. We found that blocking intrinsic Nap currents completely abolished bursting activity, demonstrating their critical role in burst onset within the network. On the other hand, blocking different combinations of synaptic receptors revealed that spectro-temporal burst properties are uniquely associated with synaptic functionality and that excitatory connectivity is necessary for the presence of network-wide bursting. In addition to confirming the critical contribution of direct excitatory effects, mixed-effects modeling also revealed distinct combined (nonlinear) contributions of excitatory and inhibitory synaptic activity to network bursting properties.
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