Houston Daily

University of Houston College of Optometry Professor John O’Brien has been awarded $2.6 million from the National Eye Institute to continue his research on electrical synapses and gap junction plasticity. This funding supports work that O’Brien has conducted for over two decades, focusing on how these structures impact not only the retina but also broader neurological functions.

Gap junctions are small tunnels that allow electrical signals to pass quickly between neurons, forming what are known as electrical synapses. These connections play a key role in how the retina processes visual information. The ability of gap junctions to adjust their strength, known as plasticity, is directed by brain signals.

Researchers have linked reduced function in electrical synapses to conditions such as autism, while excessive activity may be associated with seizures. “Of particular interest to the vision community, genome-wide association studies repeatedly link differences in DNA sequences near the gene that codes for a protein that forms gap junctions called Connexin 36 or Cx36, with refractive error development, perhaps the largest vision problem facing the world today,” said O’Brien.

Despite advances in understanding conventional synapse plasticity, knowledge about similar processes in electrical synapses remains limited. “This represents a barrier to progress in understanding the physiology that regulates both normal electrical synapse function and dysfunction related to human disorders. The research we propose will significantly advance our understanding of the molecular complexes that control the function of electrical synapses.” said O’Brien.

O’Brien’s team plans to study proteins associated with electrical synapses and analyze their roles in regulating synapse strength. “Our lab has shown that Cx36 phosphorylation (a short-term chemical modification of the protein) is a primary mechanism of plasticity, but that different circuits in the retina employ remarkably different signaling mechanisms to accomplish plasticity. This strongly suggests that electrical synapse density composition is circuit/cell type specific,” said O’Brien.

O’Brien’s contributions include demonstrating that plasticity is an intrinsic property of Cx36 with broad implications for brain function, showing its importance for adapting vision between night and day, and beginning a catalog of proteins surrounding electrical synapses conserved across species.