Stellate and pyramidal neurons in goldfish telencephalon respond differently to anoxia and GABA receptor inhibition.

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 ( V _m ) 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 (AP _f ) of the stellate neurons increased 68-fold. Furthermore, the GABA _A 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 E _GABA was below the action potential threshold (-36 mV pyramidal and -38 mV stellate neurons). Inhibition of GABA _A receptors with gabazine reversed the anoxia-mediated response. While GABA _B receptor inhibition alone did not affect the anoxic response, co-antagonism of GABA _A and GABA _B receptors (gabazine and CGP-55848) led to the generation of seizure-like activities in both neuron types. We conclude that with anoxia, V _m depolarizes towards E _GABA which increases AP _f in stellate neurons and decreases AP _f in pyramidal neurons, and that GABA plays an important role in the anoxia tolerance of goldfish brain.
(© 2017. Published by The Company of Biologists Ltd.)