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P Witkovsky

Publications and source records attributed to P Witkovsky.

93 records · Page 6Linked to original sources

The organization of dopaminergic neurons in vertebrate retinas.

A survey of the shapes of dopaminergic (DA) neurons in the retinas of representative vertebrates reveals that they are divisible into three groups. In teleosts and Cebus monkey, DA cells are interplexiform (IPC) neurons with an ascending process that ramifies to create an extensive arbor in the outer plexiform layer (OPL). All other vertebrates studied, including several primate species, have either DA amacrine cells or IPCs with an ascending process that either does not branch within the OPL or does so to a very limited degree. DA neurons of non-teleosts exhibit a dense plexus of fine caliber fibers which extends in the distal most sublamina of the inner plexiform layer (IPL). Teleosts lack this plexus. In all vertebrates, DA cells are distributed more or less evenly and at a low density (10-60 cells/mm2) over the retinal surface. Dendritic fields of adjacent DA neurons overlap. Most of the membrane area of the DA cell is contained within the plexus of fine fibers, which we postulate to be the major source of dopamine release. Thus, dopamine release can be modeled as occurring uniformly from a thin sheet located either in the OPL (teleosts) or in the distal IPL (most other vertebrates) or both (Cebus monkey). Assuming that net lateral spread of dopamine is zero, the fall of dopamine concentration with distance at right angles to the sheet (i.e. in the scleral-vitreal axis) will be exponential. The factors that influence the rate of fall-diffusion in extracellular space, uptake, and transport--are not yet quantified for dopamine, hence the dopamine concentration around its target cells cannot yet be assessed. This point is important in relation to the thresholds for activation of D1 and D2 dopamine receptors that are found on a variety of retinal cells.

Animals↗

Contributions of AMPA- and kainate-sensitive receptors to the photopic electroretinogram of the Xenopus retina.

The effects of kainate receptor-preferring glutamate ligands were tested on the electroretinogram (ERG) of the Xenopus retina. Kainate, domoic acid, and 5-iodowillardiine (20-100 microM) acted similarly in every respect. They increased peak amplitudes of the ERG a-, b-, and d-waves significantly over controls. The AMPA-specific antagonist, GYKI 53655, prevented a kainate-induced increase in ERG a- and d-waves, but was without effect on an increase in the b-wave. Once the effect of agonist on the b-wave had peaked, the ERG began to subside, leading to its nearly complete disappearance within 20 min. Prior exposure to GYKI followed by a combination of GYKI + agonist did not significantly slow the rate of b-wave disappearance. Our results indicate that (1) AMPA receptors contribute to ERG a- and d-waves. (2) The kainate-evoked increase in ERG a-, b-, and d-waves probably results, in part, from an excitotoxic swelling of inner retinal processes. (3) The inner retina has a population of GYKI-resistant, kainate-sensitive receptors which may contribute to b-wave generation.

Alanine↗

Sub-millimolar cobalt selectively inhibits the receptive field surround of retinal neurons.

Recent work has indicated that cobalt, at sub-millimolar concentrations, blocks horizontal cell (HC) to cone feedback, without attenuating direct cone to second-order cell synaptic transmission. We utilized low concentrations (0.25-0.5 mM) of cobalt to test the contribution of the feedback circuit, and other possible cobalt-sensitive mechanisms, to the receptive-field surrounds of retinal neurons. In the great majority of cases, low cobalt blocked ganglion cell surrounds, and it invariably blocked driving the ganglion cell by extrinsic current injected into the HC network. Although low cobalt reduced the integrating area of the HC network, dopamine, which similarly constricted the HC receptive area, did not block ganglion cell surrounds. Low cobalt reduced a late depolarizing wave in the HC light-evoked waveform and selectively suppressed the depolarizing component of chromatic HCs, both signs of HC to cone feedback. Low cobalt also reduced or blocked completely the receptive-field surrounds of a small sample of bipolar and amacrine cells. These results implicate the HC to cone feedback synapse in the formation of the receptive-field surround of retinal neurons.

Animals↗