The Effects of L(+), D(-), and DL-2-amino-4-phosphonobutyrate (APB) on Electroretinogram and Ganglopn Cell Activity in the Cat Retina

L(+)-, D(-)-, or DL-2-amino-4-phosphonobutyric acid (APB; 2.5- 16 μmol) were injected into the vitreous body of anesthetized adult cats. The retina was stimulated by diffuse square wave light flashes (10- 60 ms). The flash-induced electroretinogram (ERU) and responses of single retinal ganglion cells (RGC) were recorded simultaneously. Intravitreal injection of L(+)APB led to a decrease in the ERG b-wave amplitude and the unmasking of the a-wave. The magnitude and rate of the b-wave reduction were different for the two enantiomers. The threshold dose of D(-)APB was 6 times higher than for L(+)APB. L(+)APB (8.2 ± 1.6 μmol; n=7) decreased the b-wave with an average time constant r = 88.5 min, D(-)APB (13.2 ± 1.1 μmol; n=6) with r = 357.1 min, and DL-APB (8.35 ± 1.1 μmol; n=5) with r = 101.0 min. Concomitant with the reduction of the b-wave, L(+)APB (2.7μmol) inhibited both the spontaneous and light-evoked firing in ON-center ganglion cells. The threshold doses of L(+), D(-) and DL-APB for inhibition of spontaneous adivity and the light response in ON-center cells paralleled those in reducing the ERU h-wave. Low doses of L(+)APB or DL-APB that were effective in blockng ON-center cell activity caused only very small changes in the activity of OFF-center ganglion cells. However, high doses of L(+)APB (≥8.2μmol) or DL-APB (≥13.7 μmol) also decreased the spontaneous and light-evoked activity in OFF-center RGC and first shortened than prolonged the light-induced inhibition of OFF-center RGC.Whitehall Foundation (S93-24

Hardware Coupled Nonliear Oscillators as a Model of Retina

An electronic circuit consisting of coupled nonlinear oscillators⁴＇⁵ simulates the spatiotemporal processing in retina. Complex behavior recorded in vivo from ganglion cells in the cat retina 6 in response to flickering light spots is matched by setting the coupling parameters in the hardware oscillators. An electronic neuron (c-neuron) is composed of four coupled oscillators: three representing the light driven generator potential of the ganglion cell, the other representing membrane spiking. A 1-D ring of e-neurons reflects the connectivity in the retina: strong neighborhood excitation, and wider inhibition. E-neurons, like retinal ganglion cells, exhibit spontaneous spiking. Driving more than one e-neuron with a sinusoidally modulated input increases regularity in the e-neurons responses, as is found in the retina. We encoded c-neuron activity into single-bit spike trains and found chaotic spontaneous oscillations using close return histograms. The model's behavior gives a new understanding of neurophysiological findings.Whitehall (S93-24); Air Force Office of Scientific Research (F49620-92-J-0499, F49620-92-J-0334); Office of Naval Research (N00014-89-J-1377, N00014-95-I-0409); MIT Undergraduate Research Oppurtunities Progra

Nonlinearity and oscillations in X-type ganglion cells of the cat retina

Intracellularly recorded light-responses of X-type ganglion cells in the cat retina were separated, with the help of a wavelet method, into "slow" membrane ("G")-potentials and the corresponding spike trains. In response to sinusoidally modulated high intensity light spots with different sizes and frequencies, X-type ganglion cells show both oscillations correlated with the stimulus frequency and other, faster, oscillations that were not always locked to the stimulus. A forced van der Pol oscillator model with stimulus-dependent coefficients proved to describe the empirical findings quite well. A linearity-coefficient of the equations indicates strong nonlinearity at a temporal frequency of 8 Hz with spot sizes on the order of 0.5-0.7 deg and decreasing nonlinearity at lower temporal frequencies or smaller spot sizes, while the faster oscillations become more prominent. We could not determine whether the oscillations are intrinsic to the cell-membrane or generated by (or in interaction with) the preganglionic retinal meshwork. The results show that X-cell spike-trains can contain oscillations that are not phase-locked to the stimulus and that are therefore virtually invisible after stimulus synchronous averaging. It is not likely that these retinal oscillations directly induce the well described oscillations in cat visual cortex, since they usually fall in a different frequency range.</p

On the complex dynamics of intracellular ganglion cell light responses in the cat retina

We recorded intracellular responses from cat retinal ganglion cells to sinusoidal flickering lights, and compared the response dynamics with a theoretical model based on coupled nonlinear oscillators. Flicker responses for several different spot sizes were separated in a "smooth" generator (G) potential and corresponding spike trains. We have previously shown that the G-potential reveals complex, stimulus-dependent, oscillatory behavior in response to sinusoidally flickering lights. Such behavior could be simulated by a modified van der Pol oscillator. In this paper, we extend the model to account for spike generation as well, by including extended Hodgkin-Huxley equations describing local membrane properties. We quantified spike responses by several parameters describing the mean and standard deviation of spike burst duration, timing (phase shift) of bursts, and the number of spikes in a burst. The dependence of these response parameters on stimulus frequency and spot size could be reproduced in great detail by coupling the van der Pol oscillator and Hodgkin-Huxley equations. The model mimics many experimentally observed response patterns, including non-phase-locked irregular oscillations. Our findings suggest that the information in the ganglion cell spike train reflects both intraretinal processing, simulated by the van der Pol oscillator, and local membrane properties described by Hodgkin-Huxley equations. The interplay between these complex processes can be simulated by changing the coupling coefficients between the two oscillators. Our simulations therefore show that irregularities in spike trains, which normally are considered to be noise, may be interpreted as complex oscillations that might carry information.</p

The lateral spread of light adaptation in cat horizontal cell responses

To investigate the sites of light adaptation processes in the mammalian distal retina, we studied the lateral spread of adaptation signals in cone-driven cat horizontal (H-) cell responses. The size of the adaptation pool is compared to the receptive field for H-cell responses. H-cell activity was recorded intracellularly in the optically intact, in vivo eye. It is demonstrated that light adaptation as measured in H-cells is not a strictly local process. Background light falling outside a central test region effectively modulates the responses to a small test light, flashed on the receptive field center. The integration area for adaptation signals was quantitatively compared to the H-cell receptive field size by measuring the desensitizing effect of background light on the responses to a small centered test spot, as a function of background spot size. The area-adaptation function is comparable to the area-response function but has a slightly smaller length constant. Light adaptation in H-cell responses, therefore, reveals spread of adaptation over a large distance and is probably mediated through lateral interactions in the H-cell network rather than in the cones.</p

Spatial asymmetries in cat retinal ganglion cell responses

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