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The Department of Biomedicine

BBB seminar: Maximiliano L. Suster

Human-specific loss of GLRA4 reveals specialized roles of inhibitory glycine receptors in vertebrate startle and motility

Maximiliano L. Suster
Neural Circuits and Behaviour Group, Uni Research AS, Bergen

Glycine receptors (GlyRs) are pentameric ion channels made of α and β subunits critical for inhibitory neurotransmission in the brainstem and spinal cord. Mutations in GlyRα1 result in startle disease, consisting of noise or touch-induced neonatal seizures, resulting in muscle stiffness. Although the function of GlyRα1,2 and 3 subunits has received much attention, the role of GlyRα4 remains unclear. A premature stop codon found in the human GLRA4 sequence is predicted to truncate the last transmembrane domain of α4 rendering it inactive. I will present our study aimed to clarify the biological roles of α4 using a combination of molecular, physiological and behavioural data from human, chimp and zebrafish. We have found that α4 indeed plays essential roles in neuronal circuits that regulate startle and motility; however, our evidence firmly demonstrates that GlyRα4 has been selectively lost in the human lineage. This raises the possibility that specialization of inhibitory glycine receptors might have contributed to changes in reflex circuits between humans and our closest ancestors.

Chairperson: Clive R. Bramham , Department of Biomedicine