The Department of Biomedicine

BBB seminar: Margaret Lin Veruki

Glutamate transporters: a novel mechanism for presynaptic inhibition of neurotransmitter release in the central nervous system

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Margaret Lin Veruki
Neuroscience Research Group, Department of Biomedicine, University of Bergen

The goal of our laboratory is to understand and characterize the repertoire of synaptic and cellular mechanisms utilized by specific microcircuits in the central nervous system. This means that we study the activation and function of specific ion channel proteins that are involved in signal processing within small networks of neurons. We have recently focused on a retinal microcircuit that processes visual signals generated in twilight or dark-adapted conditions. This microcircuit involves three neurons, the glutamatergic rod bipolar cell and its two postsynaptic partners, the AI and the AII amacrine cells. Using patch-clamp recording of visually identified neurons in an in vitro slice preparation of the rat retina, we have discovered a unique role for a presynaptic glutamate transporter as an inhibitor of synaptic transmission (Nature Neurosci, 2006, 9: 1388-96). This transporter is located on the axon terminals of rod bipolar cells and has a large anionic conductance that is activated by synaptically released glutamate. Additionally, we found that glutamate can escape the synaptic cleft and activate glutamate transporters on neighboring cells ("spillover"). Through this mechanism, glutamate released from one bipolar cell can inhibit the release of glutamate from neighboring bipolar cells, generating a mechanism of lateral inhibition. Combining these recent results with previous studies, a picture emerges of a synaptic microcircuit where a complex and dynamic microenvironment extends the repertoire of available mechanisms used for signal processing. The functional role of a glutamate transporter as an ion channel involved in presynaptic inhibition may have general implications for signal transmission in the central nervous system.