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Updated: Aug 6, 2025
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Induction of an Isoelectric Brain State to Investigate the Impact of Endogenous Synaptic Activity on Neuronal Excitability In Vivo
Published on: March 31, 2016
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Interplay between biochemical processes and network properties generates neuronal up and down states at the
Shubhada N Joshi1, Aditya N Joshi2, Narendra D Joshi3
1National Center for Adaptive Neurotechnologies (NCAN), David Axelrod Institute, Wadsworth Center, New York State Department of Health, 120 New Scotland Ave., Albany, New York 12208, USA.
Physical Review. E
|March 18, 2023
Summary
Cellular resource availability, like ATP and glutamate, at the tripartite synapse drives neuronal up and down states. Resource limitation causes "down states," while recovery enables "up states" and network transitions.
Area of Science:
- Neuroscience
- Computational Biology
- Biochemistry
Background:
- Neuronal up and down states are observed in vitro and in vivo, with proposed functions and mechanisms lacking clear connections.
- Existing models do not fully integrate cellular biochemistry with network-level dynamics for state generation.
Purpose of the Study:
- To investigate the contribution of cellular-level biochemistry to network-level mechanisms underlying neuronal up and down states.
- To explore function-mechanism links for up and down states using a neurochemical model of the tripartite synapse.
Main Methods:
- Developed a neurochemical model of a single tripartite synapse within a network context.
- Characterized model behavior across parameter space, focusing on resource limitation (ATP, glutamate).
- Validated model against six disparate experimental systems (in vitro and in vivo).
Main Results:
- Resource limitation at the tripartite synapse leads to signal transmission failure and "down states."
- Recovery of resources facilitates signal transmission and enables "up states" or "reignition."
- Model demonstrates distinct operational "regimes" based on ATP and glutamate availability, matching experimental data without parameter changes.
Conclusions:
- Cellular ATP and glutamate availability are critical for neuronal state transitions, acting as ignition and extinction phenomena at the network level.
- The model highlights a "final common pathway" at the tripartite synapse driven by resource scarcity, potentially explaining "local sleep."
- Sleeplike behavior may be an emergent property of networks of tripartite synapses.
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