101: Volatile anesthetic effects on inhibitory synaptic transmission in rat cerebral cortex

Topic: Basic Science
Subtopic: Non-specific to any diagnosis (including studies in healthy animals), Electrophysiology

Background and Aims: The mechanisms underlying anesthetic-induced loss of consciousness are not yet fully understood. In this study, we compared the modulatory effects of the volatile anesthetic isoflurane on inhibitory synaptic transmission between inhibitory and excitatory neurons.

Methods: Experiments were conducted using VGAT-Venus rats aged postnatal day 17–30. Acute cortical brain slices were prepared using standard procedures, and simultaneous whole-cell patch-clamp recordings were obtained from multiple neurons. Cells were classified as fast-spiking interneurons (FSNs) or pyramidal neurons (PNs) based on Venus expression and electrophysiological properties in response to square current injections. Paired recordings were established in which presynaptic FSNs formed inhibitory synaptic connections with nearby FSNs or PNs. We assessed the effects of 3% isoflurane on unitary inhibitory postsynaptic currents (uIPSCs) evoked by presynaptic action currents and recorded from postsynaptic neurons.

Results: In FSN-to-FSN connections, isoflurane decreased uIPSC amplitude, whereas the half-width of the uIPSCs was not significantly altered. As a result, overall charge transfer in FSN-to-FSN connections remained unchanged. In contrast, in FSN-to-PN connections, isoflurane reduced uIPSC amplitude. However, it significantly prolonged the half-width of the uIPSCs, leading to increased charge transfer. These results demonstrate that isoflurane differentially modulates inhibitory synaptic transmission depending on the postsynaptic neuron type.

Conclusions: Isoflurane exhibited distinct modulatory effects on inhibitory synaptic transmission depending on the type of postsynaptic neuron, suggesting that it may suppress the activity of excitatory PNs more strongly than that of inhibitory FSNs.

References: Koyanagi Y, Oi Y, Yamamoto K, Koshikawa N, Kobayashi M (2014) Fast-spiking cell to pyramidal cell connections are the most sensitive to propofol-induced facilitation of GABAergic currents in rat insular cortex. Anesthesiology 121, 68-78.

Presenting Author: Yuko Koyanagi
Submitting Author: Yuko Koyanagi

Senior Author: Masayuki Kobayashi

IASP 2026 Global Year theme of Neuropathic Pain: No

• Keisuke Kaneko: DDS, PhD - Nihon University School of Dentistry
• Eiko Yokota: DDS, PhD - Nihon University School of Dentistry
• Mie Kajiwara: DDS, PhD - Nihon University School of Dentistry
• Takashi Hitosugi: DDS, PhD - Nihon University School of Dentistry
• Masayuki Kobayashi: DDS, PhD - Nihon University School of Dentistry