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 GABAA receptor 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 as EGABA was below the action potential threshold (-36 mV pyramidal and -38 mV stellate neurons). Inhibition of GABAA receptors with gabazine reversed the anoxia-mediated response. While GABAB receptor inhibition alone did not affect the anoxic response, co-antagonism of GABAA and GABAB receptors (gabazine and CGP-55848) led to the generation of seizure-like activities in both neuron types. We conclude that with anoxia, Vm depolarizes towards EGABA which increases APf in stellate neurons and decreases APf in pyramidal neurons, and that GABA plays an important role in the anoxia tolerance of goldfish brain.

• Authors: Nariman Hossein-Javaheri, Michael P Wilkie, Wudu E Lado, Leslie T Buck
• Journal: The Journal of experimental biology (J Exp Biol) Vol. 220 Issue Pt 4 Pg. 695-704 (02 15 2017) ISSN: 1477-9145 [Electronic] England
• PMID: 27923876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017. Published by The Company of Biologists Ltd.

Chemical References

• Fish Proteins
• GABA-A Receptor Antagonists
• GABA-B Receptor Antagonists
• Receptors, GABA-A
• Receptors, GABA-B
• Oxygen

Topics

• Action Potentials (drug effects)
• Anaerobiosis
• Animals
• Fish Proteins (metabolism)
• GABA-A Receptor Antagonists (pharmacology)
• GABA-B Receptor Antagonists (pharmacology)
• Goldfish (physiology)
• Humans
• Hypoxia (metabolism)
• Oxygen (metabolism)
• Patch-Clamp Techniques
• Pyramidal Cells (cytology, drug effects, metabolism)
• Receptors, GABA-A (metabolism)
• Receptors, GABA-B (metabolism)
• Telencephalon (cytology, physiology)