The James L. O'Leary Prize recognizes outstanding research performed by a predoctoral or postdoctoral student in the Washington University Program in Neuroscience. 

2005 O'Leary Prize Recipients:

Post Doctorate Category:  Botir Sagdullaev PhD (Peter Lukasiewicz lab)

Pre Doctorate Category: shared by Ethan Graf (Anne Marie Craig lab) and John Fryer (David Holtzman lab)

The official award presentations will take place at the Bishop lecture, May 19th 2005 at 4pm

Abstracts of Presentations:

Asymmetric modulation of glutamate release in the retina.   Botir Sagdullaev, PhD. A popular concept in neurobiology is that sensory information is processed in the CNS over parallel channels of neurons that encode separate stimulus attributes. For example, in olfactory system different odorant receptors sense a particular type of odorants and send their signals to specific targets in the brain. Auditory signals are separated based on their frequency components in the inner ear; nociceptve and tactile information is conveyed from body surface to spinal cord over different populations of somatosensory afferents. Similarly, the separation of visual cues into parallel circuits is a dominant organizing theme of the visual system .

The separation of visual signals occurs at the very first retinal synapse. The light-evoked photoreceptor signals diverge onto separate bipolar cells via distinct synapses, giving rise to ON and OFF visual channels.   Physiologically, this translates into one's ability to encode either increments or decrements of light in the visual scene. After the initial separation, these two pathways are thought to be symmetric with equal and opposite light responses.   However, our findings suggest that ON and OFF pathways display significant functional asymmetries. We found that transmission to retinal ganglion cells in the second synaptic layer of the retina was differentially modulated by GABA C receptor-mediated inhibition.   Inhibitory input via GABA C receptors selectively modulates glutamate release from ON bipolar cells, limiting ‘spillover' activation of NMDA receptors at ON, but not OFF, retinal ganglion cells. We show that this mediates wider dynamic response ranges in ON, compared to OFF retinal ganglion cells and, hence, underlies the asymmetries in certain output characteristics of ON and OFF channels.

The Neurexin-Neuroligin Link Mediates Both GABAergic and Glutamatergic Synaptogenesis by Ethan Graf.  Formation of synaptic connections between nerve cells in the brain requires alignment of neurotransmitter receptors on postsynaptic dendrites opposite matching transmitter release sites on presynaptic axons. b -Neurexins and neuroligins are thought to form a trans-synaptic link at glutamate synapses, initiating the formation of the synapse by actively aligning glutamate pre- and post- synaptic components. Previously, neuroligins were shown to induce vesicle clustering in glutamatergic axons, but the ability of neurexin to induce clustering of postsynaptic proteins remained unexplored. We have now shown that neurexin alone is sufficient to induce glutamate postsynaptic differentiation in contacting dendrites. Surprisingly, and most unexpectedly, neurexin also induces GABA postsynaptic differentiation. This is the first demonstration of the ability of any protein to cluster GABA receptors and postsynaptic scaffolding proteins. Similarly, neuroligins induce presynaptic differentiation in both glutamate and GABA axons. Neuroligin-1 had previously been localized to glutamate synapses, suggesting an obvious link to glutamatergic postsynaptic differentiation, but the mechanism mediating GABAergic postsynaptic induction in particular remained elusive. We showed that while neuroligins-1, -3, and -4 localize to glutamate postsynaptic sites, neuroligin-2 localizes primarily to GABA synapses. Direct aggregation of neuroligins revealed a linkage of neuroligin-2 to GABA and glutamate postsynaptic proteins, but the other neuroligins only to glutamate postsynaptic proteins. Furthermore, mislocalized expression of neuroligin-2 disperses postsynaptic proteins and disrupts synaptic transmission. Our findings indicate that the neurexin-neuroligin link is a core component mediating both GABAergic and glutamatergic synaptogenesis, and differences in isoform localization and binding affinities may contribute to appropriate differentiation and specificity.