@article{7908,
  abstract     = {Volatile anesthetics are widely used for surgery, but neuronal mechanisms of anesthesia remain unidentified. At the calyx of Held in brainstem slices from rats of either sex, isoflurane at clinical doses attenuated EPSCs by decreasing the release probability and the number of readily releasable vesicles. In presynaptic recordings of Ca2+ currents and exocytic capacitance changes, isoflurane attenuated exocytosis by inhibiting Ca2+ currents evoked by a short presynaptic depolarization, whereas it inhibited exocytosis evoked by a prolonged depolarization via directly blocking exocytic machinery downstream of Ca2+ influx. Since the length of presynaptic depolarization can simulate the frequency of synaptic inputs, isoflurane anesthesia is likely mediated by distinct dual mechanisms, depending on input frequencies. In simultaneous presynaptic and postsynaptic action potential recordings, isoflurane impaired the fidelity of repetitive spike transmission, more strongly at higher frequencies. Furthermore, in the cerebrum of adult mice, isoflurane inhibited monosynaptic corticocortical spike transmission, preferentially at a higher frequency. We conclude that dual presynaptic mechanisms operate for the anesthetic action of isoflurane, of which direct inhibition of exocytic machinery plays a low-pass filtering role in spike transmission at central excitatory synapses.},
  author       = {Wang, Han Ying and Eguchi, Kohgaku and Yamashita, Takayuki and Takahashi, Tomoyuki},
  issn         = {15292401},
  journal      = {Journal of Neuroscience},
  number       = {21},
  pages        = {4103--4115},
  publisher    = {Society for Neuroscience},
  title        = {{Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms}},
  doi          = {10.1523/JNEUROSCI.2946-19.2020},
  volume       = {40},
  year         = {2020},
}

@article{7339,
  abstract     = {Cytoskeletal filaments such as microtubules (MTs) and filamentous actin (F-actin) dynamically support cell structure and functions. In central presynaptic terminals, F-actin is expressed along the release edge and reportedly plays diverse functional roles, but whether axonal MTs extend deep into terminals and play any physiological role remains controversial. At the calyx of Held in rats of either sex, confocal and high-resolution microscopy revealed that MTs enter deep into presynaptic terminal swellings and partially colocalize with a subset of synaptic vesicles (SVs). Electrophysiological analysis demonstrated that depolymerization of MTs specifically prolonged the slow-recovery time component of EPSCs from short-term depression induced by a train of high-frequency stimulation, whereas depolymerization of F-actin specifically prolonged the fast-recovery component. In simultaneous presynaptic and postsynaptic action potential recordings, depolymerization of MTs or F-actin significantly impaired the fidelity of high-frequency neurotransmission. We conclude that MTs and F-actin differentially contribute to slow and fast SV replenishment, thereby maintaining high-frequency neurotransmission.},
  author       = {Piriya Ananda Babu, Lashmi and Wang, Han Ying and Eguchi, Kohgaku and Guillaud, Laurent and Takahashi, Tomoyuki},
  issn         = {15292401},
  journal      = {Journal of neuroscience},
  number       = {1},
  pages        = {131--142},
  publisher    = {Society for Neuroscience},
  title        = {{Microtubule and actin differentially regulate synaptic vesicle cycling to maintain high-frequency neurotransmission}},
  doi          = {10.1523/JNEUROSCI.1571-19.2019},
  volume       = {40},
  year         = {2020},
}