How is neural circuit specificity achieved?
The highly stereotyped synaptic connections found in the nervous system were described over a century ago in the seminal Neuron Theory work by Ramon y Cajal. These “special connectional relationships” between synaptic partners form the basis of all motor movements, the acquisition and retrieval of memories, the processing of visual cues, and even our consciousness. Even though we have connectome data for many circuits, including whole animals (C. elegans), how this connectivity is formed during development remains one of the great challenges in neurobiology. The Carrillo laboratory is focused on understanding how specificity is accomplished during neural circuit formation. In order to gain insights into the wiring specificity, we use the highly tractable genetic system Drosophila melanogaster. Even in a “simple” system like Drosophila, developmental programs must instruct thousands of interneurons in the ventral nerve cord to recognize their appropriate postsynaptic motor neuron targets (Research Topic 1). Similar, but numerically less daunting, specificity challenges are encountered in the Drosophila neuromuscular system where 32 motor neurons in the VNC send their projections to the periphery where they must decide which of the 30 muscle fibers to innervate (Research Topic 2). We seek to identify the genes and mechanisms controlling these hard-wired circuits and to understand how the circuit responds to perturbations in connectivity. Our initial focus is on cell surface proteins, particularly on two subfamilies of the immunoglobulin superfamily: the Dprs and DIPs. Finally, after the proper muscle targets have been innervated, there is an orchestration of pre- and postsynaptic growth that must be regulated in order to maintain synaptic efficacy. We will investigate if/how the same genes which are used for targeting also function in synaptic growth (Research Topic 3). Overall, these studies will shed light on the developmental programs utilized not only in invertebrate systems, but also by higher order organisms that encounter similar challenges in neural circuit formation.