title: Spike Timing Rigidity Is Maintained in Bursting Neurons under Pentobarbital-Induced Anesthetic Conditions.
abstract: Pentobarbital potentiates γ-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission by prolonging the open time of GABAAreceptors. However, it is unknown how pentobarbital regulates cortical neuronal activities via local circuitsin vivo. To examine this question, we performed extracellular unit recording in rat insular cortex under awake and anesthetic conditions. Not a few studies apply time-rescaling theorem to detect the features of repetitive spike firing. Similar to these methods, we define an average spike interval locally in time using random matrix theory (RMT), which enables us to compare different activity states on a universal scale. Neurons with high spontaneous firing frequency (>5 Hz) and bursting were classified as HFB neurons (n= 10), and those with low spontaneous firing frequency (<10 Hz) and without bursting were classified as non-HFB neurons (n= 48). Pentobarbital injection (30 mg/kg) reduced firing frequency in all HFB neurons and in 78% of non-HFB neurons. RMT analysis demonstrated that pentobarbital increased in the number of neurons with repulsion in both HFB and non-HFB neurons, suggesting that there is a correlation between spikes within a short interspike interval (ISI). Under awake conditions, in 50% of HFB and 40% of non-HFB neurons, the decay phase of normalized histograms of spontaneous firing were fitted to an exponential function, which indicated that the first spike had no correlation with subsequent spikes. In contrast, under pentobarbital-induced anesthesia conditions, the number of non-HFB neurons that were fitted to an exponential function increased to 80%, but almost no change in HFB neurons was observed. These results suggest that under both awake and pentobarbital-induced anesthetized conditions, spike firing in HFB neurons is more robustly regulated by preceding spikes than by non-HFB neurons, which may reflect the GABAAreceptor-mediated regulation of cortical activities. Whole-cell patch-clamp recording in the IC slice preparation was performed to compare the regularity of spike timing between pyramidal and fast-spiking (FS) neurons, which presumably correspond to non-HFB and HFB neurons, respectively. Repetitive spike firing of FS neurons exhibited a lower variance of ISI than pyramidal neurons both in control and under application of pentobarbital, supporting the above hypothesis.
authors.affiliation: Department of Pharmacology, School of Dentistry, Nihon UniversityChiyoda, Japan; Division of Oral and Craniomaxillofacial Research, Dental Research Center, School of Dentistry, Nihon UniversityChiyoda, Japan.
authors.forename: Risako
authors.initials: R
authors.lastname: Kato
authors.affiliation: Department of Physics, College of Science and Technology, Nihon University Chiyoda, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Yamanaka
authors.affiliation: Department of Pharmacology, School of Dentistry, Nihon UniversityChiyoda, Japan; Department of Anesthesiology, School of Dentistry, Nihon UniversityChiyoda, Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Yokota
authors.affiliation: Department of Pharmacology, School of Dentistry, Nihon UniversityChiyoda, Japan; Division of Oral and Craniomaxillofacial Research, Dental Research Center, School of Dentistry, Nihon UniversityChiyoda, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Koshikawa
authors.affiliation: Department of Pharmacology, School of Dentistry, Nihon UniversityChiyoda, Japan; Division of Oral and Craniomaxillofacial Research, Dental Research Center, School of Dentistry, Nihon UniversityChiyoda, Japan; Molecular Dynamics Imaging Unit, RIKEN Center for Life Science TechnologiesKobe, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000758:Anesthesia; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology*; D055724:Electrophysiological Phenomena / Q000187:drug effects* / Q000502:physiology*; D018757:GABA Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D010424:Pentobarbital / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018757:GABA Modulators; D010424:Pentobarbital
keywords: GABAA receptor; barbiturate; insular cortex; interspike interval; unfolding transformation