91破解版 College of Optometry Professor John O鈥橞rien, a leading expert on retinal neuroscience, has received $2.6 million from the National Eye Institute to continue more than 20 years of research on electrical synapses and gap junction plasticity, which affects not just the retina, but also a wide range of other neurological functions.
In the interconnected web of information that flows through the brains of humans and other species, the little tunnels called gap junctions do a lot of heavy lifting, speedily transferring electrical signals from one neuron to the next and profoundly influencing how the retina extracts and processes a visual scene. Forming a type of synapse called an 鈥渆lectrical synapse,鈥� the plasticity of gap junctions allows them to change synapse strength as directed by a brain signal.
Reduced function of electrical synapses has been proposed to underlie autism, while their hyperfunction may lead to seizure.
鈥淥f 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,鈥� said O鈥橞rien.
Despite the progress made in understanding how plasticity of conventional synapses works, knowledge of the equivalent processes in electrical synapses is remarkably limited.
鈥淭his 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.鈥� said O鈥橞rien.
O鈥橞rien and team will examine the dense assembly of proteins that are associated with electrical synapses and control electrical synapse strength.
鈥淥ur 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,鈥� said O鈥橞rien.
The team will identify the proteins and examine how each of them impacts electrical synapses.
O鈥橞rien鈥檚 expertise in the field is well noted:
- He showed that plasticity is an intrinsic property of Cx36, with implications for the function of most electrical synapses throughout the brain
- He showed how this plasticity is essential for night and day vision, allowing the retina to adjust sensitivity and sharpen images
- He has started to build a catalog of the core set of proteins surrounding electrical synapses that are conserved across species