Prazosin is effective for combat-related PTSD with trauma nightmares in active-duty soldiers, and benefits are clinically meaningful. Substantial residual symptoms suggest that studies combining prazosin with effective psychotherapies might demonstrate further benefit.

A retinal ganglion cell commonly expresses two spatially overlapping receptive field mechanisms. One is the familiar "center/surround," which sums excitation and inhibition across a region somewhat broader than the ganglion cell's dendritic field. This mechanism responds to a drifting grating by modulating firing at the drift frequency (linear response). Less familiar is the "nonlinear" mechanism, which sums the rectified output of many small subunits that extend for millimeters beyond the dendritic field. This mechanism responds to a contrast-reversing grating by modulating firing at twice the reversal frequency (nonlinear response). We investigated this nonlinear mechanism by presenting visual stimuli to the intact guinea pig retina in vitro while recording intracellularly from large brisk and sluggish ganglion cells. A contrast-reversing grating modulated the membrane potential (in addition to the firing rate) at twice the reversal frequency. This response was initially hyperpolarizing for some cells (either ON or OFF center) and initially depolarizing for others. Experiments in which responses to bars were summed in-phase or out-of-phase suggested that the single class of bipolar cells (either ON or OFF) that drives the center/surround response also drives the nonlinear response. Consistent with this, nonlinear responses persisted in OFF ganglion cells when ON bipolar cell responses were blocked by L-AP-4. Nonlinear responses evoked from millimeters beyond the ganglion cell were eliminated by tetrodotoxin. Thus, to relay the response from distant regions of the receptive field requires a spiking interneuron. Nonlinear responses from different regions of the receptive field added linearly.

In the classic "What the frog's eye tells the frog's brain," Lettvin and colleagues showed that different types of retinal ganglion cell send specific kinds of information. For example, one type responds best to a dark, convex form moving centripetally (a fly). Here we consider a complementary question: how much information does the retina send and how is it apportioned among different cell types? Recording from guinea pig retina on a multi-electrode array and presenting various types of motion in natural scenes, we measured information rates for seven types of ganglion cell. Mean rates varied across cell types (6-13 bits . s(-1)) more than across stimuli. Sluggish cells transmitted information at lower rates than brisk cells, but because of trade-offs between noise and temporal correlation, all types had the same coding efficiency. Calculating the proportions of each cell type from receptive field size and coverage factor, we conclude (assuming independence) that the approximately 10(5) ganglion cells transmit on the order of 875,000 bits . s(-1). Because sluggish cells are equally efficient but more numerous, they account for most of the information. With approximately 10(6) ganglion cells, the human retina would transmit data at roughly the rate of an Ethernet connection.

The potential and actual connections between rod and rod bipolar arrays in the area centralis of the cat retina were studied by electron microscopy of serial ultrathin sections. In the region studied there were about 378,000 rods/mm2 and 36,000-47,000 rod bipolars/mm2. The tangential spread of rod bipolar dendrites was 11.2 microns in diameter, and the "coverage factor" for the rod bipolar cell was 3.5-4.6. We estimate that about 37 rods potentially converge on a rod bipolar cell and that one rod potentially diverges to about four rod bipolar cells. The actual connections, however, are less than this by about half: 16-20 rods actually converge on a bipolar cell and one rod actually diverges to slightly less than two rod bipolar cells. The degree of convergence appears to reflect a compromise between the need to signal graded stimulus intensities (requiring wide convergence) and the need to maintain a good signal/noise ratio (requiring narrow convergence). Amacrine varicosities that provide reciprocal contact at the rod bipolar dyad were studied in serial electron microscopic autoradiograms following intraocular administration of 3H-GABA or 3H-glycine. More that 90% of the reciprocal amacrine processes accumulated GABA in a specific fashion. This information, in conjunction with Nelson's recordings from the rod bipolar and amacrine cells postsynaptic at the dyad (Nelson et al: Invest. Ophthalmol. 15:946-953, '76; Kolb and Nelson: Vision Res. 23:301-312, '83), suggests that feedback at the rod bipolar output might be positive.

GABA and glycine provide excitatory action during early development: they depolarize neurons and increase intracellular calcium concentration. As neurons mature, GABA and glycine become inhibitory. This switch from excitation to inhibition is thought to result from a shift of intracellular chloride concentration ([Cl-]i) from high to low, but in retina, measurements of [Cl-]i or chloride equilibrium potential (ECl) during development have not been made. Using the developing mouse retina, we systematically measured [Cl-]i in parallel with GABA's actions on calcium and chloride. In ganglion and amacrine cells, fura-2 imaging showed that before postnatal day (P) 6, exogenous GABA, acting via ionotropic GABA receptors, evoked calcium rise, which persisted in HCO3- -free buffer but was blocked with 0 extracellular calcium. After P6, GABA switched to inhibiting spontaneous calcium transients. Concomitant with this switch we observed the following: 6-methoxy-N-ethylquinolinium iodide (MEQ) chloride imaging showed that GABA caused an efflux of chloride before P6 and an influx afterward; gramicidin-perforated-patch recordings showed that the reversal potential for GABA decreased from -45 mV, near threshold for voltage-activated calcium channel, to -60 mV, near resting potential; MEQ imaging showed that [Cl-]i shifted steeply around P6 from 29 to 14 mM, corresponding to a decline of ECl from -39 to -58 mV. We also show that GABAergic amacrine cells became stratified by P4, potentially allowing GABA's excitatory action to shape circuit connectivity. Our results support the hypothesis that a shift from high [Cl-]i to low causes GABA to switch from excitatory to inhibitory.