title: Stellate and pyramidal neurons in goldfish telencephalon respond differently to anoxia and GABA receptor inhibition.
abstract: With oxygen deprivation, the mammalian brain undergoes hyper-activity and neuronal death while this does not occur in the anoxia-tolerant goldfish (Carassius auratus). Anoxic survival of the goldfish may rely on neuromodulatory mechanisms to suppress neuronal hyper-excitability. As γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, we decided to investigate its potential role in suppressing the electrical activity of goldfish telencephalic neurons. Utilizing whole-cell patch-clamp recording, we recorded the electrical activities of both excitatory (pyramidal) and inhibitory (stellate) neurons. With anoxia, membrane potential (Vm) depolarized in both cell types from -72.2 mV to -57.7 mV and from -64.5 mV to -46.8 mV in pyramidal and stellate neurons, respectively. While pyramidal cells remained mostly quiescent, action potential frequency (APf) of the stellate neurons increased 68-fold. Furthermore, the GABAAreceptor reversal potential (E-GABA) was determined using the gramicidin perforated-patch-clamp method and found to be depolarizing in pyramidal (-53.8 mV) and stellate neurons (-42.1 mV). Although GABA was depolarizing, pyramidal neurons remained quiescent asEGABAwas below the action potential threshold (-36 mV pyramidal and -38 mV stellate neurons). Inhibition of GABAAreceptors with gabazine reversed the anoxia-mediated response. While GABABreceptor inhibition alone did not affect the anoxic response, co-antagonism of GABAAand GABABreceptors (gabazine and CGP-55848) led to the generation of seizure-like activities in both neuron types. We conclude that with anoxia,Vmdepolarizes towardsEGABAwhich increases APfin stellate neurons and decreases APfin pyramidal neurons, and that GABA plays an important role in the anoxia tolerance of goldfish brain.
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, 25 Harbord St, Toronto, ON, Canada M5S 3G5.
authors.forename: Nariman
authors.initials: N
authors.lastname: Hossein-Javaheri
authors.affiliation: Department of Biology, Wilfred Laurier University, 75 University Avenue West, Waterloo, ON, Canada N2L 3C5.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Wilkie
authors.affiliation: Department of Neurobiology, University of Alabama at Birmingham, 1825 University Blvd, Birmingham, AL 35294-2182, USA.
authors.forename: Wudu E
authors.initials: WE
authors.lastname: Lado
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, 25 Harbord St, Toronto, ON, Canada M5S 3G5 les.buck@utoronto.ca.
authors.forename: Leslie T
authors.identifier: 0000-0002-2637-7821
authors.initials: LT
authors.lastname: Buck
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000693:Anaerobiosis; D000818:Animals; D029941:Fish Proteins / Q000378:metabolism*; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D006054:Goldfish / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology / Q000502:physiology
chemical_list: D029941:Fish Proteins; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D010100:Oxygen
keywords: Action potential; Action potential frequency; EGABA; Membrane potential; Spike frequency; Whole-cell conductance