Connexins and Electrical Synapses in the Retina and Brain

Many neurons establish electrical synapses, termed. gap junctions, instead of or in addition to chemical synapses.  In the retina, electrical synapses are thought to regulate the transmission of signals from rod photoreceptors although the details of the circuits involved remain controversial.  To define the nature of these circuits, we are using targeted gene ablation to remove connexins from subsets of retinal neurons.  To test the effect on rod signaling, light-evoked responses from genetically altered retinas are characterized using electrophysiological approaches.

A role for electrical synapses has also been suggested in the regulation of neuronal precursor proliferation, differentiation and/or circuit formation.  It is generally accepted that coordinated activity among groups of neurons is critical to the proper establishment of neuronal circuitry.  However, the number of conventional chemical synapses formed  during prenatal development in vertebrate organisms can be <1% of the number found in adults.  Thus, gap junctions, which are abundantly detected in neuronal precursors, provide an attractive mechanism for the coordination of cell activity between cells prior to the widespread development of chemical synapses and action potentials.  For example, a substantial amount of correlative evidence suggests that connexins regulate precuror proliferation during cortical development.  We are directly testing this hypothesis, using a combination of in vivo and in vitro studies to investigate conditional connexin knockout animals that target particular subsets of cells in the developing cortex.



Period of Support: 8/1/04 - 3/31/13