Thomas R. Clandinin
Making Connections in the Central Nervous System
My laboratory has two main interests. First, we would like to understand how genetically hard-wired mechanisms specify remarkably precise patterns of inter-neuronal connections during development. Second, using genetic approaches, we would like to functionally dissect the neuronal circuits that underlie visual processing tasks like flow-field motion detection, object approach and color perception. To address these questions, we use the fruit fly visual because it displays both an extremely precise pattern of neuronal connections and because it mediates a rich behavioral repertoire.
As in any other visual system, photoreceptors in the fly eye that see the same point in space converge onto a common set of neuronal targets. However, because of the unusual optics of the compound eye, photoreceptors that see the same point in space are distributed over the retinal surface. As a result, a complex pattern of connections between photoreceptors and their primary targets is required to reconstruct visual space within the fly brain. Remarkably, this complex pattern of connections appears to be genetically hard-wired and is entirely independent of visual input. An ongoing forward genetic screen aimed at identifying the molecular pathways required for these targeting events has identified two members of the cadherin superfamily as well as a protein tyrosine phosphatase as playing critical roles. We anticipate that interactions between these proteins, as well as many as-yet unidentified components, will ultimately define a core set of mechanisms important for determining how a growth cone chooses amongst alternate synaptic partners.
Flies have a rich visual experience, perceiving color and motion, recognizing objects and detecting the polarization state of light. Reflecting these perceptual capabilities, the fly optic lobe contains a wealth of neuron types connected in complex (and poorly defined) circuits. Electrophysiological studies in other insects have identified neurons whose response properties, such preferences for horizontal back-to-front motion, reflect complex integration of visual cues. Our goal is to identify sets of neurons required for a number of distinct visual behaviors, trace their connection patterns and, using genetic methods to prevent neurotransmission in these cells, determine their specific role in each behavior. We are currently developing a forward genetic screen to identify sets of neurons based on their behavioral function.