GABA receptor inhibition and severe hypoxia induce a paroxysmal depolarization shift in goldfish neurons.

Nariman Hossein-Javaheri, Leslie Thomas Buck

Journal of neurophysiology 2021 Feb 01

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Mammalian neurons undergo rapid excitotoxic cell death when deprived of oxygen; however, the common goldfish (Carassius auratus) has the unique ability of surviving in oxygen-free waters, under anoxia. This organism utilizes γ-amino butyric acid (GABA) signaling to suppress excitatory glutamatergic activity during anoxic periods. Although GABAA receptor antagonists are not deleterious to the cellular survival, coinhibition of GABAA and GABAB receptors is detrimental by abolishing anoxia-induced neuroprotective mechanisms. Here we show that blocking the anoxic GABAergic neurotransmission induces seizure-like activity (SLA) analogous to a paroxysmal depolarization shift (PDS), with hyperpolarization of action potential (AP) threshold and elevation of threshold currents. The observed PDS was attributed to an increase in excitatory postsynaptic currents (EPSCs) that are normally attenuated with decreasing oxygen levels. Furthermore, for the first time, we show that in addition to PDS, some neurons undergo depolarization block and do not generate AP despite a suprathreshold membrane potential. In conclusion, our results indicate that with severe hypoxia and absence of GABA receptor activity, telencephalic neurons of C. auratus manifest a paroxysmal depolarization shift, a key feature of epileptic discharge.NEW & NOTEWORTHY This work shows that the combination of anoxia and inhibition of GABA receptors induces seizure-like activities in goldfish telencephalic pyramidal and stellate neurons. Importantly, to prevent seizure-like activity, an intact GABA-mediated inhibitory pathway is required.

Citation

Nariman Hossein-Javaheri, Leslie Thomas Buck. GABA receptor inhibition and severe hypoxia induce a paroxysmal depolarization shift in goldfish neurons. Journal of neurophysiology. 2021 Feb 01;125(2):321-330