“Knocking out” a Neural Circuit

Although the visual system occupies nearly half of the mammalian brain, we still do not completely understand its first synaptic stage. One reason is that the dendrites postsynaptic to photoreceptors comprise such a maze of fine processes that doubt remains whether all the second order circuits have been identified—even after 4 decades of electron microscopy. Now advanced functional methods applied to a mammalian rod pathway suggest a circuit previously unsuspected from anatomy. The standard model for two rod circuits is shown in the diagram. The rod terminal contacts a single type of dedicated bipolar cell (left) and also forms an electrical junction with the cone terminal. The rod-to-bipolar circuit is thought to serve starlight, which is so dim that over minutes no rod transduces more than one photon. This single-photon signal requires huge amplification, which renders the circuit vulnerable to saturation in brighter light. The rod-to-cone circuit is thought to serve twilight, which is bright enough that over one second a rod tranduces tens to hundreds of photons. This multi-Two Rod Pathways to Ganglion Cells photon signal can thus " piggyback " onto the cone bipo-lar circuit (Smith et al., 1986). will certainly trigger a search for the anatomical sub-Now, Soucy and colleagues (1998) in the September strate. The diagram suggests a cone bipolar cell that issue of Neuron have used diphtheria toxin controlled also collects from rods, as reported briefly for gray squir-by a cone-selective promoter to produce a coneless rel (West, 1978). Such a connection might explain how mouse. The retina, except for the absence of cones and a human " achromat, " born essentially coneless, never-cone-driven responses, looks essentially normal. Bipo-theless possesses a functional multi-photon rod path-lar cells that normally collect from cones remain intact, way (Stockman et al., 1995). which is somewhat surprising, because neurons com-The present results do not contradict the standard monly degenerate when deprived of their primary input. version of the " twilight circuit " that routes the multi-But most surprising is that the multi-photon rod signal photon rod signal via an electrical synapse to the cone. still reaches ganglion cells. Since this signal cannot take This signal, identified by its rod action spectrum and the expected route, from rod via gap junctions to cone, time course, is recorded in cat and monkey directly from the rod must excite an unknown type of bipolar cell. The simplest experiment conceptually would have Furthermore, since …