Structurally, a synapse is most simply defined as a site of close membrane apposition between two neurons, the presynaptic neuron containing a cluster of vesicles associated with an active zone while the postsynaptic neuron has apposing receptors. In practice, synapses come in a bewildering diversity of shapes and sizes each characteristic of a CNS region. The goal of my work is to understand how the characteristic shape of a synapse determines its function.
In the mammalian retina, cone photoreceptors contact Off bipolar cells at sites called basal junctions (Fig. 1). At these junctions, the membranes of pre- and postsynaptic cells come into close apposition, but there are no presynaptic docked vesicles and no active zones. Rather, it appears that transmitter is released only at synaptic ribbons and must diffuse extracellularly over a long and tortuous course to reach receptors at the basal contact. In order to study transmission at the cone synapse while preserving its structure, I have developed a slice preparation from the cone-dominant retina of the ground squirrel (Fig. 2). In this preparation, two voltage clamps are used to simultaneously control the membrane voltages of the cone and a postsynaptic Off bipolar cell. By voltage clamping both cells, it is possible to study rapid synaptic events such as transmitter diffusion in the cleft, receptor activation, and receptor desensitization. The results indicate that a long diffusion path may serve to reduce the noise inherent in the quantization of transmitter release. Noise reduction is important since cones signal light intensity with graded changes in membrane potential.
Fig. 1 Diagram of the cone pedicle showing basal contacts (BC), an invaginating contact (IC), horizontal cell processes (H), and a synaptic ribbon (Rb).
Fig. 2 Cone to On bipolar cell synaptic transmission. a. The fluorescence in the bipolar cell is superimposed onto a Nomarski micrograph of the retinal slice. b. The fluorescence of sulforhodamine 101 (red) in the bipolar cell and of BODIPY 492/515 in the cone (green) are superimposed. c. Postsynaptic response produced when the coneÍs membrane voltage was stepped from -70 to 0 mV. Bipolar cell held at -70 mV. Ganglion cells, GC; inner plexiform layer, IPL; inner nuclear layer, INL; outer plexiform layer, OPL; photoreceptors, PR.