Regulation of synaptic mGluR7 by protein interactions with the autism risk gene, Elfn1.

Dr. Tevye Stachniak
Department of Biomedical Sciences 
Memorial University 

Date: March 11, 2024
Time: 1:00 p.m. to 2:00 p.m. 
Room: CSF 1302

Abstract:

Nervous system development involves both activity-dependent and genetically determined processes that match the excitation of nervous tissue with an appropriate balance of inhibition. Disruption to this balance can result in disability, including autism. The autism risk genes, Elfn1 and mGluR7, work together at excitatory synapses onto somatostatin (SOM) interneurons to produce delayed feedback inhibition. SOM inhibition is then robustly recruited by high frequency excitatory activity, serving as an inhibitory “emergency brake” to halt runaway excitation. To create this delayed inhibition, Elfn1 promotes dimerization of mGluR7 to generate constitutive, agonist-independent mGluR7 activity. As a result, Elfn1/mGluR7 protein complexes exhibit atypical pharmacological properties, such as biased g protein signaling. Further, synaptic recruitment of SOM interneurons can be enhanced by the presence of presynaptic kainate receptors, dynamically tuning delayed inhibition to match brain activity levels. Loss of function of Elfn1/mGluR7 complexes may thus contribute to the hyperexcitability, sensory hypersensitivity, and epilepsy risk characteristic of autism spectrum disorders.