Synaptic circuitry of the retina and olfactory bulb

Steven H. DeVries and Denis A. Baylor Department of Neurobiology Fairchild Science Center Stanford University School of Medicine Stanford, California 94305 The retina and olfactory bulb offer unique windows on the synaptic mechanisms of the brain. The wiring of both struc- tures is known in detail and the sensory input can be quan- titatively controlled. Synaptic operations can be examined in a clear functional context, for the nature of the informa- tion being processed is well-defined. The performance of the networks is remarkable. Rod photoreceptors in the dark adapted retina respond to single quanta of light en- ergy, while a flash causing five quantal absorptions makes itself felt in consciousness. Retinal circuits compute the contrast, motion, and color of visual scenes, adjusting their sensitivity and time resolution in accord with widely chang- ing conditions. The olfactory epithelium and olfactory bulb transduce small numbers of airborne odorant molecules into signals that produce sensations * of smell and allow thousands of odors to be distinguished. Messages exiting the olfactory bulb specify the identity and intensity of odor sources in the outside world. We examine the circuitry and synaptic mechanisms of the retina and olfactory bulb, concentrating on recent advances and emphasizing themes that may illuminate the workings of other regions of the nervous system. Circuits and Signal Flow in the Retina and Olfactory Bulb The anatomical relations between some of the principal cells in the retina and olfactory epithelium/bulb are shown in Figure 1. In the retina (Figure 1A), the photoreceptor cells--rods and cones--convert light energy into graded membrane hyperpolarizations. The molecular mechanism that generates the hyperpolarization has recently been reviewed (Kaupp and Koch, 1992; Lagnado and Baylor, 1992). The rods mediate vision at low light levels, while the cones mediate vision in ordinary daylight and provide for sensations of color. At the synaptic endings of rods and cones, the hyperpolarization lowers the rate of release of the transmitter, glutamate. Gap junctions allow voltage changes generated in one photoreceptor to spread to otl~ Rods and cones make synapses on retinal bipolar and horizontal cells. The horizontal cells, laterally extended interneurons of the outer plexiform layer, regulate signal flow from photoreceptors to bipolar cells. The decrease in glutamate release from photoreceptors causes the hori- zontal cells to hyperpolarize. This response is generated by a reduction in the activity of glutamate receptors, which, in the presence of ligand, partially depolarize the hori- zontal cell membrane. Horizontal cells are interconnected by electrical junctions and release 7-aminobutyric acid (GABA) at feedback synapses on photoreceptor terminals. Bipolar cells relay messages from photoreceptors to reti- nal ganglion cells, whose axons form the optic nerve, as well as to amacrine cells, interneurons of the inner plexi- form layer. One type of bipolar cell hyperpolarizes when light falls on the photoreceptors contacting it, while a sec- ond type depolarizes. The hyperpolarizing response is generated by a mechanism similar to that in horizontal cells, while the depolarizing response is triggered by a different mechanism, which, when glutamate is bound, closes channels that would otherwise depolarize the cell. In some animals, the depolarizing response to cone input appears to be generated by a third mechanism in which glutamate opens channels that hyperpolarize the cell (Saito et al., 1979; Nawy and Copenhagen, 1987). Both hyperpolarizing and depolarizing bipolar cells release glu- tamate at their synaptic terminals (Tachibana and Okada, 1991). Whereas photoreceptor, horizontal, and bipolar cells re- spond only with slow, graded changes in membrane poten- tial, ganglion bells and some amacrine cells generate spikes. The amacrine cells are a diverse group of laterally oriented interneurons that control information flow from bipolars to retinal ganglion cells at the inner plexiform layer. Ganglion cells transmit visual information through the optic nerve to the thalamus or midbrain. One common type of ganglion cell (ON in Figure 1A) is excited by a local cluster of depolarizing bipolar cells. It encodes the brightness of a small region relative to the surround. An- other type (OFF) is excited by a cluster of hyperpolarizing bipolars and encodes the darkness of a small region rela- tive to the surround. Olfactory receptors (Figure 1B) are located in the olfac- tory epithelium, which lines the nasal cavity. Here they are exposed to airborne odorants. Projecting from each receptor cell is a series of long cilia embedded in the mu- cus next to the airstream. These cilia bear odorant recep- tors, which, upon binding odor molecules, trigger enzy- matic events that cause cationic channels to open and depolarize the membrane. The depolarization spreads passively over the soma to the axon hillock, where it initi- ates action potentials. The molecular mechanism of olfac- tory transduction has recently been reviewed (Lancet, 1992; Reed, 1992). Several enzymatic cascades have been implicated. In the best established, the receptor acti- vates a GTP-binding protein (G~f), which activates adenyl- ate cyclase. Cyclic AMP levels in the cell rise, and cyclic AMP directly opens nucleotide-gated cationic channels. Axons from olfactory receptors enter the olfactory nerve and terminate in spherical neuropils just below the surface of the bulb. In these neuropils, the olfactory glomeruli, terminals of olfactory receptor cells are presynaptic to den- drites of mitral and tufted cells, neurons whose axons pro- ject out of the bulb, and periglomerular cells. This wiring is strongly convergent, mitral/tufted cells being three or- ders of magnitude less numerous than receptor neurons. Periglomerular cells make reciprocal synapses with mitral cell dendrites in the glomeruli. Just central to the glomeruli