Highly correlated neural activity in the form of spontaneous waves of action potentials is present in the developing retina weeks before vision. Optical imaging revealed that these waves consist of spatially restricted domains of activity that form a mosaic pattern over the entire retinal ganglion cell layer. Whole-cell recordings indicate that wave generation requires synaptic activation of neuronal nicotinic acetylcholine receptors on ganglion cells. The only cholinergic cells in these immature retinas are a uniformly distributed bistratified population of amacrine cells, as assessed by antibodies to choline acetyltransferase. The results indicate that the major source of synaptic input to retinal ganglion cells is a system of cholinergic amacrine cells, whose activity is required for wave propagation in the developing retina.

1. Intracellular and extracellular recordings were made from rat olfactory bulb mitral and tufted cells during odor stimulation and during electrical stimulation of the olfactory nerve. Neurons were identified by horseradish peroxidase injections and/or antidromic activation. The presentation of multiple concentrations of at least one odorant in a cyclic artificial sniff paradigm, as reported previously (10), allowed the study of odor responses. This approach was extended to multiple odorants to compare their concentration-response profiles. This procedure avoids the problems of interpretation resulting from nonequivalence of the effective concentrations of different odorants used as stimuli that have characterized previous studies of odor quality effects. Comparisons of intracellular events and responses to electrical stimulation with the odor-induced spike train activity allow us to begin to delineate the local circuitry involved in generating odor-induced responses. 2. The concentration-response profiles of the 72 cells in the present study are comparable to those previously reported for output neurons of the olfactory bulb, showing ordered changes in the temporal patterning of spike activity with step changes in odor concentration. However, eight of the neurons exhibited inhibitory responses to lower concentrations, but excitation, at similar latency, to higher concentrations of the same odorant. These data emphasize that to study pattern changes induced by changing odor quality the influence of stimulus intensity must also be carefully examined. The data also provide evidence that the temporal pattern evoked by an odorant is probably not in itself the code for odor quality recognition. 3. Complete concentration-response profiles, including subthreshold concentrations, to more than one odorant show that, although responses to the different odorant can evolve systematically with concentration, the responses to different odorants can evolve through very different patterns. For example, in some cells, the response patterns to different odors were complementary in form. These results demonstrate that the patterned responses of olfactory bulb neurons can reflect changes in odor quality as well as intensity. 4. Intracellular recording was employed to compare the temporal patterning of spikes during odor stimulation with membrane potential changes. In some cases, the spike pattern was closely correlated with apparent postsynaptic potentials. However, there were several clear exceptions. In five cells, a prominent hyperpolarization, seen in the first sniff of a series of 10 consecutive sniffs, was associated with pauses in spike activity. In the following

1. Intracellular recordings were made from 28 granule cells and 6 periglomerular cells of the rat olfactory bulb during odor stimulation and electrical stimulation of the olfactory nerve layer (ONL) and lateral olfactory tract (LOT). Neurons were identified by injection of horseradish peroxidase (HRP) or biocytin and/or intracellular response characteristics. Odorants were presented in a cyclic sniff paradigm, as reported previously. 2. All interneurons could be activated from a wide number of stimulation sites on the ONL, with distances exceeding their known dendritic spreads and the dispersion of nerve fibers within the ONL, indicating that multisynaptic pathways must also exist at the glomerular region. All types of interneurons also responded to odorant stimulation, showing a variety of responses. 3. Granule cells responded to electrical stimulation of the LOT and ONL as reported previously. However, intracellular potential, excitability, and conductance analysis suggested that the mitral cell-mediated excitatory postsynaptic potential (EPSP) is followed by a long inhibitory postsynaptic potential (IPSP). An early negative potential, before the EPSP, was also observed in every granule cell and correlated with component I of the extracellular LOT-induced field potential. We have interpreted this negativity as a "field effect," that may be diagnostic of granule cells. 4. Most granule cells exhibited excitatory responses to odorant stimulation. Odors could produce spiking responses that were either nonhabituating (response to every sniff) or rapidly habituating (response to first sniff only). Other granule cells, while spiking to electrical stimulation, showed depolarizations that did not evoke spikes to odor stimulation. These depolarizations were transient with each sniff or sustained across a series of sniffs. These physiological differences to odor stimulation correlated with granule cell position beneath the mitral cell layer for 12 cells, suggesting that morphological subtypes of granule cells may show physiological differences. Some features of the granule cell odor responses seem to correlate with some of the features we have observed in mitral/tufted cell intracellular recordings. Only one cell showed inhibition to odors. 5. Periglomerular (PG) cells showed a response to ONL stimulation that was unlike that found in other olfactory bulb neurons. There was a long-duration hyperpolarization after a spike and large depolarization or burst of spikes (20-30 ms in duration). Odor stimulation produced simple bursts of action potentials, Odor stimulation produced simple bursts of action potentials, suggesting that PG cells may simply follow input from the olfactory nerve.(ABSTRACT TRUNCATED AT 400 WORDS)

Pulse-like currents resembling miniature postsynaptic currents were recorded in patch-clamped isolated cones from the tiger salamander retina. The events were absent in isolated cones without synaptic terminals. The frequency ofevents was increased by either raising the osmotic pressure or depolarizing the cell. It was decreased by the application of either glutamate or the glutamate-transport blockers dihydrokainate and D,L-threo-3-hydroxyaspartate. The events required external Na+ for which Li' could not substitute. The reversal potential of these currents followed the equilibrium potential for Cl-when internal Cl-concentration was changed. Thus, these miniature currents appear to represent the presynaptic activation of the glutamate receptor with glutamate transporter-like pharmacology, caused by the photoreceptor's own vesicular glutamate release. Using a noninvasive method to preserve the intracellular Cl-concentration, we showed that glutamate elicits an outward current in isolated cones. Fluorescence of the membrane-permeable form of fura-2 was used to monitor Ca2+ entry at the cone terminal as a measure of membrane depolarization. The increase in intracellular Ca2+ concentration, elicited by puff application of 30 mM KCI, was completely suppressed in the presence of 100 ,iM glutamate. Puff application of glutamate alone had no measurable depolarizing effect. These results suggest that the equilibrium potential for Cl1, Ecl, was more negative than the activation range for Ca2+ channels and that glutamate elicited an outward current, hyperpolarizing the cones.