Synchronicity of pyramidal neurones in the neocortex dominates isoflurane-induced burst suppression in mice.
Summary
Using EEG and micro-endoscopic calcium imaging in mice, the authors show that isoflurane-induced burst suppression is dominated by synchronized cortical pyramidal neuron activity. Chemogenetic manipulation of parvalbumin interneurons bidirectionally modulated this synchrony, whereas SST/Vip interneurons and subcortical structures showed minimal correlation.
Key Findings
- Burst suppression under isoflurane closely tracks synchronous activity of cortical excitatory pyramidal neurons (~65% positively correlated).
- Minimal or absent correlation with inhibitory interneuron synchrony and subcortical neuronal activity.
- Chemogenetic activation or inhibition of PV interneurons bidirectionally decreased or increased cortical synchrony (P<0.0001), whereas SST/Vip manipulation had no such effect.
Clinical Implications
Refining EEG depth-of-anesthesia interpretation and exploring PV-interneuron–targeted modulation could enhance brain-state control during deep anesthesia or refractory status epilepticus management.
Why It Matters
This work identifies a neuronal circuit mechanism for a fundamental EEG signature under deep anesthesia, offering targets to monitor or modulate brain states intraoperatively and in critical care.
Limitations
- Mouse model findings may not fully generalize to human anesthesia.
- Detailed sample sizes and replication across anesthetic agents are not provided in the abstract.
Future Directions
Translate findings to human intraoperative EEG-ECog paradigms; test whether targeted modulation of PV interneurons or downstream pathways can prevent or shape burst suppression.
Study Information
- Study Type
- Case-control
- Research Domain
- Pathophysiology
- Evidence Level
- V - Preclinical mechanistic animal study; outside traditional clinical evidence hierarchy.
- Study Design
- OTHER