A better understanding of inhibitory synapses in the mammalian retina
September’s featured paper is "Synaptic Vesicle Exocytosis at the Dendritic Lobules of an Inhibitory Interneuron in the Mammalian Retina" published in Neuron. The paper is by a team from the von Gersdorff Lab.
The leading cause of blindness in American adults comes from what might be a surprising source – complications from diabetes. Diabetic eye disease can cause severe vision loss or blindness and is caused by damage to the retina.
Recent studies have found that malfunctioning neurons and synapses in the retina can lead to loss of vision. This month’s highlighted paper sheds further insight onto the mechanisms of retinal function and provides hope that in the future, researchers can gain a deeper understanding of damage that may be incurred in pre-diabetic patients.
“Understanding how neurons talk to each other is key to understanding how our brains work,” said Mary Heinricher, Ph.D., associate dean for basic research in the OHSU School of Medicine. “But it's incredibly hard to tease out what is happening in the neuron that is sending the signal versus the neuron receiving the signal."
“We wanted to investigate the function and properties of inhibitory synapses in the retina,” said Henrique von Gersdorff, Ph.D., senior scientist at the Vollum Institute. “Work by a group in Norway found that diabetes can lead to loss of vision because of malfunctioning neurons and synapses in the retina. In order to develop treatment strategies for prevascular diabetic retinopathy, a better understanding of the inhibitory synapses in the retina is needed because these synapses are some of the first to go awry.”
“Although we know that loss of proper synaptic strength in inhibitory synapses leads to excessive synaptic excitation via the release of too much glutamate, little is known about the properties of inhibitory synapses in the mammalian retina," said Dr. von Gersdorff.
“The von Gersdorff laboratory used a challenging technique to focus in on exactly what is happening on the presynaptic side in a specific population of retinal inhibitory neurons,” said Dr. Heinricher. Their work was recently published in the journal Neuron.
“We were able to investigate the properties of neurotransmitter release from a particular class of small inhibitory interneurons in the retina that regulate visual responses,” said Dr. von Gersdorff. “We studied these neurons during early postnatal development and during stimulation of the retina with different light levels. This was only possible because of our close collaboration with the labs of Drs. Puthussery and Taylor, who are experts in measuring light responses from retinal neurons. We studied a specific sub-class of inhibitory interneuron using an exquisitely sensitive technique that measures minute changes in the surface area of neurons that reflect the release of neurotransmitters. We were able to measure changes of less that 1 percent in the neuron’s surface area for the first time.”
The results from the Puthussery, Taylor and von Gersdorff labs reveal that interneurons release glycine in small and graded amounts when weak light is applied to the retina, and that these neurons are capable of surprisingly robust and sustained glycine release when exposed to a bright flash of light. “This group of interneurons is thus able to inhibit excessive glutamate release from nearby excitatory neurons,” said Dr. von Gersdorff.
“Diabetic retinopathy is known to disrupt these inhibitory interneurons,” added Dr. von Gersdorff. “Our new recording techniques will allow researchers to directly test new drugs that modulate glycine release from these interneurons and may lead to exciting new avenues for treatment of diabetic retinopathy at an early stage, before it has caused major damage.”
The von Gersdorff laboratory is now poised to test several drugs that modulate the release of neurotransmitter from inhibitory cells in the retina. “We hope some of these drugs will prove promising in modulating the inhibitory synapses,” said Dr. von Gersdorff. “This may lead to treatment strategies that reduce excessive glutamate release in the retina, which can lead to some of the early effects of diabetic retinopathy and perhaps also glaucoma, two devastating diseases of the retina.”
CitationSynaptic Vesicle Exocytosis at the Dendritic Lobules of an Inhibitory Interneuron in the Mammalian RetinaNeuron. 2015 Aug 5;87(3):563-75. doi: 10.1016/j.neuron.2015.07.016.Veera Balakrishnan, Teresa Puthussery, Mean-Hwan Kim, W. Rowland Taylor, and Henrique von Gersdorff
Pictured above: (clockwise from top left) Veera Balakrishnan, Teresa Puthussery, Rowland Taylor, Henrique von Gersdorff, Mean-Hwan Kim.
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About the School of Medicine Paper of the Month
The OHSU School of Medicine spotlights a recently published faculty research paper each month. The goals are to describe to the public the exceptional research happening at OHSU as well as inform our faculty of the innovative work underway across the school’s departments, institutes and disciplines. The monthly paper is selected by Associate Dean for Basic Research Mary Heinricher, Ph.D.