title: Fast-spiking cell to pyramidal cell connections are the most sensitive to propofol-induced facilitation of GABAergic currents in rat insular cortex.
abstract: BACKGROUND
  Propofol facilitates γ-aminobutyric acid-mediated inhibitory synaptic transmission. In the cerebral cortex, γ-aminobutyric acidergic interneurons target both excitatory pyramidal cells (Pyr) and fast-spiking (FS) and non-FS interneurons. Therefore, the propofol-induced facilitation of inhibitory transmission results in a change in the balance of excitatory and inhibitory inputs to Pyr. However, it is still unknown how propofol modulates γ-aminobutyric acidergic synaptic transmission in each combination of Pyr and interneurons.
  
  
  METHODS
  The authors examined whether propofol differentially regulates inhibitory postsynaptic currents (IPSCs) depending on the presynaptic and postsynaptic cell subtypes using multiple whole cell patch clamp recording from γ-aminobutyric acidergic interneurons and Pyr in rat insular cortex.
  
  
  RESULTS
  Propofol (10 μM) consistently prolonged decay kinetics of unitary IPSCs (uIPSCs) in all types of inhibitory connections without changing paired-pulse ratio of the second to first uIPSC amplitude or failure rate. The FS→Pyr connections exhibited greater enhancement of uIPSC charge transfer (2.2 ± 0.5 pC, n = 36) compared with that of FS→FS/non-FS connections (0.9 ± 0.2 pC, n = 37), whereas the enhancement of charge transfer in non-FS→Pyr (0.3 ± 0.1 pC, n = 15) and non-FS→FS/non-FS connections (0.2 ± 0.1 pC, n = 36) was smaller to those in FS→Pyr/FS/non-FS. Electrical synapses between FS pairs were not affected by propofol.
  
  
  CONCLUSIONS
  The principal inhibitory connections (FS→Pyr) are the most sensitive to propofol-induced facilitation of uIPSCs, which is likely mediated by postsynaptic mechanisms. This preferential uIPSC enhancement in FS→Pyr connections may result in suppressed neural activities of projection neurons, which in turn reduces excitatory outputs from cortical local circuits.
authors.affiliation: From the Department of Anesthesiology (Y.K., Y.O.), and Department of Pharmacology (K.Y., N.K., M.K.), Nihon University School of Dentistry, Tokyo, Japan; Division of Immunology and Pathobiology (Y.K., Y.O.), and Division of Oral and Craniomaxillofacial Research (K.Y., N.K., M.K.), Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan; and Molecular Dynamics Imaging Unit, RIKEN Center for Life Science Technologies, Kobe, Japan (M.K.).
authors.forename: Yuko
authors.initials: Y
authors.lastname: Koyanagi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Oi
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Noriaki
authors.initials: N
authors.lastname: Koshikawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018755:GABA Agonists; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D007395:Interneurons / Q000187:drug effects; D008297:Male; D018408:Patch-Clamp Techniques; D015742:Propofol / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D055647:Rats, Transgenic; D018079:Receptors, GABA / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects
chemical_list: D018686:Anesthetics, Intravenous; D018755:GABA Agonists; D050485:GABA Plasma Membrane Transport Proteins; D018079:Receptors, GABA; D015742:Propofol