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The Anoxic Reduction of Mitochondrial ROS Production Leads to Increased GABAergic Interneuron Activity and Electrical Suppression in Turtle Cerebral Cortex
Author(s) -
Hawrysh Peter,
Hogg David,
Buck Les
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.760.18
Subject(s) - gabaergic , excitatory postsynaptic potential , glutamate receptor , depolarization , interneuron , inhibitory postsynaptic potential , membrane potential , mitochondrion , biology , reactive oxygen species , mitochondrial ros , neurotransmission , patch clamp , chemistry , neuroscience , biophysics , microbiology and biotechnology , electrophysiology , biochemistry , receptor
The anoxia‐tolerant western painted turtle ( Chrysemys picta bellii) has uniquely adapted to surviving extended periods of low O 2 by reducing the activity of energy‐consuming pathways. The largest such pathway is the re‐establishment of neuronal ionic gradients following excitatory transmission. We hypothesize that the mitochondria serve as the initiator of neuronal silencing by sensing changes in O 2 and triggering increased GABA release with the goal of reducing overall energetic demand. Here, we show that the reduction of mitochondrial O 2 consumption during anoxia limits the production of reactive oxygen species (ROS), as evidenced by a fluorescence reduction of the ROS‐sensitive dye DCF during anoxia. Whole‐cell patch clamp recordings demonstrate that this reduction in ROS enhances both tonic and phasic post‐synaptic GABA A receptor currents. To determine how the reduction in ROS affects GABA release, we first determined the location of neurons that produce and release GABA. Fast‐spiking GABA‐releasing stellate interneurons were found to sparsely reside in the molecular and subcellular layers of the turtle cortex, based in immunohistochemical staining for glutamate decarboxylase and the voltage‐sensitive K + channel subunit Kv3.1. These neurons fire action potential bursts at a frequency of 0.09 ± 0.01 Hz, which is the same frequency that GABAergic phasic currents occur in pyramidal neurons. Following the transition to anoxia or during pharmacological ROS scavenging with N‐acetylcysteine, stellate interneurons depolarize and become more excitable, as evidenced by the increased prevalence of action potentials between and during bursts. These results suggest that mitochondrial ROS signaling in stellate interneurons controls widespread GABAergic signaling in the turtle cortex. Support or Funding Information Research was supported by an Ontario Graduate Scholarship to Peter Hawrysh and a Discovery Accelerator Supplements NSERC grant to Les Buck.