Distinct expressions of contrast gain control in parallel synaptic pathways converging on a retinal ganglion cell.

Visual neurons adapt to increases in stimulus contrast by reducing their response sensitivity and decreasing their integration time, a collective process known as 'contrast gain control.' In retinal ganglion cells, gain control arises at two stages: an intrinsic mechanism related to spike generation, and a synaptic mechanism in retinal pathways. Here, we tested whether gain control is expressed similarly by three synaptic pathways that converge on an OFF alpha/Y-type ganglion cell: excitatory inputs driven by OFF cone bipolar cells; inhibitory inputs driven by ON cone bipolar cells; and inhibitory inputs driven by rod bipolar cells. We made whole-cell recordings of membrane current in guinea pig ganglion cells in vitro. At high contrast, OFF bipolar cell-mediated excitatory input reduced gain and shortened integration time. Inhibitory input was measured by clamping voltage near 0 mV or by recording in the presence of ionotropic glutamate receptor (iGluR) antagonists to isolate the following circuit: cone --> ON cone bipolar cell --> AII amacrine cell --> OFF ganglion cell. At high contrast, this input reduced gain with no effect on integration time. Mean luminance was reduced 1000-fold to recruit the rod bipolar pathway: rod --> rod bipolar cell --> AII cell --> OFF ganglion cell. The spiking response, measured with loose-patch recording, adapted despite essentially no gain control in synaptic currents. Thus, cone bipolar-driven pathways adapt differently, with kinetic effects confined to the excitatory OFF pathway. The ON bipolar-mediated inhibition reduced gain at high contrast by a mechanism that did not require an iGluR. Under rod bipolar-driven conditions, ganglion cell firing showed gain control that was explained primarily by an intrinsic property.

Disinhibition combines with excitation to extend the operating range of the OFF visual pathway in daylight.

Cone signals divide into parallel ON and OFF bipolar cell pathways, which respond to objects brighter or darker than the background and release glutamate onto the corresponding type of ganglion cell. It is assumed that ganglion cell excitatory responses are driven by these bipolar cell synapses. Here, we report an additional mechanism: OFF ganglion cells were driven in part by the removal of synaptic inhibition (disinhibition). The disinhibition played a relatively large role in driving responses at low contrasts. The disinhibition persisted in the presence of CNQX and d-AP-5. Furthermore, the CNQX/d-AP-5-resistant response was blocked by l-AP-4, meclofenamic acid, quinine, or strychnine but not by bicuculline. Thus, the disinhibition circuit was driven by the ON pathway and required gap junctions and glycine receptors but not ionotropic glutamate or GABA(A) receptors. These properties implicate the AII amacrine cell, better known for its role in rod vision, as a critical circuit element through the following pathway: cone --> ON cone bipolar cell --> AII cell --> OFF ganglion cell. Rods could also drive this circuit through their gap junctions with cones. Thus, to light decrement, AII cells, driven by electrical synapses with ON cone bipolar cells, would hyperpolarize and reduce glycine release to excite OFF ganglion cells. To light increment, the AII circuit would directly inhibit OFF ganglion cells. These results show a new role for disinhibition in the retina and suggest a new role for the AII amacrine cell in daylight vision.

The effect of the fiber curvature gradient on break excitation in cardiac tissue.

BACKGROUND: Break excitation has been hypothesized as a mechanism for the initiation of reentry in cardiac tissue. One way break excitation can occur is by virtual electrodes formed due to a curving fiber geometry. In this article, we are concerned with the relationship between the peak gradient of fiber curvature and the threshold for break stimulation and the initiation of reentry. METHODS: We calculate the maximum gradient of fiber curvature for different scales of fiber geometry in a constant tissue size (20x20 mm), and also examine the mechanisms by which reentry initiation fails. RESULTS: For small peak gradients, reentry fails because break excitation does not occur. For larger peak gradients, reentry fails because break excitation fails to develop into full-scale reentry. For strong stimuli above the upper limit of vulnerability, reentry fails because the break excitation propagates through the hyperpolarized region and then encounters refractory tissue, causing the wave front to die.

How the spatial frequency of polarization influences the induction of reentry in cardiac tissue.

UNLABELLED: Influences of spatial frequency of polarization. INTRODUCTION: The mechanism by which an electric field induces a rotor during cross-field stimulation of cardiac tissue is not entirely known. Different heterogeneous aspects of cardiac tissue have been offered as possible theories, a prominent one being fiber curvature. The polarization produced when an electric field is applied to a sheet of tissue is varied over many spatial frequencies, depending upon the fiber angle. This article compares the effect of high and low spatial frequencies of polarization on reentry induction. METHODS AND RESULTS: We incorporate a randomized fiber angle geometry into a two-dimensional active cardiac tissue model with unequal anisotropy ratios already exhibiting smooth, curving fibers. We simulate cross-field stimulation to initiate reentry in the tissue model, and compare the electric field thresholds at different S1-S2 intervals for tissue with randomized fiber angles, tissue with a smooth fiber geometry, and tissue with randomized fiber angles plus smooth, curving fibers. The tissue with both small, random fiber angles and curving fibers has a significantly lower threshold for reentry at certain intervals on the strength-interval curve than for the two cases individually. CONCLUSION: Cardiac tissue exhibiting a random fiber geometry in conjunction with a smooth fiber geometry includes high and low spatial frequencies of polarization that may have an effect on the mechanism for reentry at certain S1-S2 intervals. Low spatial frequency regions of hyperpolarization carve out excitable pathways, and high spatial frequency regions provide the large gradient of transmembrane potential required to initiate break excitation.

Effect of plunge electrodes in active cardiac tissue with curving fibers.

OBJECTIVES: Our goal is to determine if plunge electrodes change how the heart responds to electrical stimulation. BACKGROUND: Several experiments designed to study the induction of a rotor in cardiac tissue have used plunge electrodes to measure the transmural potential. It is our hypothesis that these electrodes may have affected the electrical response of the tissue to a shock. METHODS: We previously have shown that a single plunge electrode in two-dimensional, passive cardiac tissue induces a significant transmembrane potential when stimulated by a large shock. In this study, we expand our simulation to include an array of nine electrodes in active tissue with curving fibers. We compare the thresholds for rotor induction in tissue with and without electrodes by initiating a planar S1 wavefront and then stimulating the tissue at different intervals with a uniform S2 electric field perpendicular to S1. In tissue without plunge electrodes, virtual electrode polarization due to the curving fibers is generally widespread over the entire tissue, whereas polarization tends to be localized around the electrodes in tissue including them. RESULTS: Our results show that at some S1-S2 intervals, the presence of plunge electrodes can result in reentry when it otherwise would not be possible. For other S1-S2 intervals, such as during the vulnerable period when the reentry threshold is at a minimum, the induction of reentry is unaffected by the presence of plunge electrodes. CONCLUSIONS: Plunge electrodes can play an important role during the stimulation of cardiac tissue, but this is highly dependent on the chosen S1-S2 interval.