Differences in amplitude-voltage relations between minimal and composite mossy fibre responses of rat CA3 hippocampal neurons support the existence of intrasynaptic ephaptic feedback in large synapses.

Computer simulations and electrophysiological experiments have been performed to test the hypothesis on the existence of an ephaptic interaction in purely chemical synapses. According to this hypothesis, the excitatory postsynaptic current would depolarize the presynaptic release site and further increase transmitter release, thus creating an intrasynaptic positive feedback. For synapses with the ephaptic feedback, computer simulations predicted non-linear amplitude-voltage relations and voltage dependence of paired-pulse facilitation. The deviation from linearity depended on the strength of the feedback determined by the value of the synaptic cleft resistance. The simulations showed that, in the presence of the intrasynaptic feedback, recruitment of imperfectly clamped synapses and synapses with linear amplitude-voltage relations tended to reduce the non-linearity and voltage dependence of paired-pulse facilitation. Therefore, the simulations predicted that the intrasynaptic feedback would particularly affect small excitatory postsynaptic currents induced by activation of electrotonically close synapses with long synaptic clefts. In electrophysiological experiments performed on hippocampal slices, the whole-cell configuration of the patch-clamp technique was used to record excitatory postsynaptic currents evoked in CA3 pyramidal cells by activation of large mossy fibre synapses. In accordance with the simulation results, minimal excitatory postsynaptic currents exhibited "supralinear" amplitude-voltage relations at hyperpolarized membrane potentials, decreases in the failure rate and voltage-dependent paired-pulse facilitation. Composite excitatory postsynaptic currents evoked by activation of a large amount of presynaptic fibres typically bear linear amplitude-voltage relationships and voltage-independent paired-pulse facilitation. These data are consistent with the hypothesis on a strong ephaptic feedback in large mossy fibre synapses. The feedback would provide a mechanism whereby signals from large synapses would be amplified. The ephaptic feedback would be more effective on synapses activated in isolation or together with electrotonically remote inputs. During synchronous activation of a large number of neighbouring inputs, suppression of the positive intrasynaptic feedback would prevent abnormal boosting of potent signals.

Horizontal cell dynamics: what are the main factors?

The factors potentially determining the dynamics of horizontal cell (HC) responses are: (1) the rate of transmitter release (including its transient component) and removal; (2) the voltage non-linearity of HC non-synaptic membrane combined with its capacitance; and (3) the dynamics of feedback from HCs to photoreceptors. Using, in consecutive order, the models of an isolated HC, a HC with one or two synaptic inputs and a HC of chromatic type, we have analysed the relative importance of three factors in shaping HC responses to the light and electrical current. The most prominent effect on the shape of HC ON responses derives from the voltage-dependency of the non-synaptic membrane. The dynamics of synaptic transmission plays a leading role in shaping the OFF light responses. For depolarizing responses of C-type HCs, the key factor is the electrical feedback from L-type HCs, which provides not only the response of opposite polarity (to red light), but also the typical feedback delay.

Spread of potentials along the network of horizontal cells in the retina of the turtle.

The spread of potentials along electrically-coupled horizontal cell networks in the turtle retina was studied at different levels of illumination. The mean values of the stationary space constant, lambda st, measured by the steady-state responses to a bar of light moved along the retina, is about 0.13 mm for the LII horizontal cell response and 0.35 mm for the LI response. lambda st is quite stable in the physiological range of membrane potentials. The dynamic space constant, lambda (t), measured at different intervals after the onset of the light bar, transiently increased during the rising phase of the on-response. Such a transient change of lambda (t) is absent or less apparent for depolarizing responses to the offset of the light bar. Ba2+ ions strongly enhanced the transient increase of lambda (t) for hyperpolarizing responses without affecting lambda (t) for depolarizing responses. Possible mechanisms of the transient increase of the dynamic space constant are discussed.

Electrical feedback mechanism in the processing of signals in the outer plexiform layer of the retina.

In any chemical synapse there is an electrical feedback initiated by the electrical current generated by the postsynaptic neurone. We argue that this feedback can be rather effective in the case of invaginating synapses in the retina. A model of a dyad synapse (cone-horizontal cell-bipolar cell) is developed, in which the transfer function between the cone and bipolar cell is modulated by the synaptic current of the horizontal cell. This modulation originates by the change of the potential drop along the intercellular gap between the cone and the horizontal cell. The model takes into account the electrical coupling between the horizontal cells as well as the nonlinearity of their nonsynaptic (somatic) membrane. The model reproduces qualitatively the steady-state responses of an hyperpolarizing bipolar cell to the light spot and an annulus. It gives also the adaptational (with a light background) shift of the cone-bipolar cell transfer function. The model can be applied to depolarizing bipolar cells and to C-type horizontal cells.

Photoreceptor coupling and boundary detection.

Electrical coupling between photoreceptors results in the extensive spreading of output potentials along the syncytium of photoreceptor terminals. This smoothing of output potentials seems to make spatial resolution worse. However, the photoreceptor noise that is considered to be non-correlated both in space and time is smoothed to the greater extent than the correlated potential difference across the boundaries between areas of different brightness. This improves the signal-to-noise ratio more for more extended boundaries and favours lowering the threshold so that they can be detected more easily during the subsequent processing. The results have a striking parallel with a well known dependence of contrast threshold on stimulus size as measured psychophysically.

Spectral characteristics of photoreceptors and horizontal cells in the retina of the Siberian sturgeon Acipenser baeri Brandt.

In the retina of Siberian sturgeon, three spectral classes of photoreceptors were identified by microspectrophotometry. These were rods, oil drop-containing and oil drop-free cones possessing P549, and oil drop-containing cones possessing P613 and P465. With intracellular recordings, rod-driven, cone-driven, and mixed horizontal cells of luminosity type were found, as well as color-opponent horizontal cells of, at least, 6 kinds. Biphasic R/G cells received hyperpolarizing input either from rods or from green cones; in R/B cells, it was from blue cones. Other three types comprised biphasic G/B (or Y/B), RG/B, and triphasic G/BR cells. So the Chondrostean retina has the color-processing circuitry common for all ray-finned fishes.

[Model of electrical feedback mechanisms through chemical synapses]. / Model' mekhanizma obratnoi sviazi cherez élektricheskii tok v khimicheskom sinapse.

The model of excitatory chemical synapse is proposed in which the feed-back between the post- and presynaptic neurones is carried out by means of synaptic current generated by postsynaptic neurone. In the model, the potential drop generated by this current along the intercellular gap near the activated synapse (RIII) evokes additional depolarization of presynaptic membrane and thus stimulates the additional release of transmitter (fig. 1, A and B). The feed-back, which increases the steepness of transfer function between pre- and postsynaptic neurones is the more effective the higher the resistance of intercellular gap (fig. 2 and 3, B). is very low, so that activation of synapse is unable to change significantly its membrane potential (V2), the feed-back is the most effective, as revealed in additional depolarization of presynaptic membrane (VII in fig. 3, A). In inhibitory synapse the feed-back by electrical current is negative one.

[Model of a neuron-regulator of the effectiveness of synaptic transmission]. / Model' neirona-reguliatora éffektivnosti sinapticheskoi peredachi.

In diad and triad synapses of vertebrate retina the transmitter released from one and the same presynaptic membrane can act simultaneously on two (or even three) postsynaptic neurones. The model of such a diad synapse is proposed, in which the positive electrical feed-back is caried out between one of postsynaptic and presynaptic neurones. The feed-back appears because of potential drop across the longitudinal resistance of intercellular gap (RIII) near the activated synapse (see [1]). It is shown that if the input resistance of this postsynaptic neurone (N3) is low (low R3 in fig. 1,), it can operate as a regulator of effectiveness of synaptic transmission between the presynaptic (N1) and the second postsynaptic (N2) neurones. The effectiveness of synpatic transmission (e. g. the steepness of transfer function) is the more, the higher the membrane potential in the neurone acting as a regulator (fig. 2), and the higher the resistance of intercellular gap (RIII) (fig. 2). The model reproduces the effect of polarization of horizontal cells (by means of light or current) on the membrane potential in bipolars of the turtle and fish retina (fig. 3). The analysis of the model also shows that one of the functions of horizontal cells, as regulators of synaptic transmission between photoreceptors and bipolars, may be the detection of small objects and borders of image against uniform background.

[Voltage dependence of the cobalt-induced blockage of synaptic transmission between the photoreceptors and horizontal cells of the retina]. / Potentsialozavisimost' blokirovaniia kobal'tom sinapticheskoi peredachi mezhdu fotoretseptorami i gorizontal'nymi kletkami setchatki.

Synaptic transmission between photoreceptors and horizontal cells (HC) in the turtle retina blocked by Co2+ ions can be restored by constant radial current passed through the retina and depolarizing presynaptic receptor terminals. This result is not related with the action of current on horizontal cells themselves because their depolarization through the intracellular microelectrode did not restore the response to light. The restoring effect of presynaptic depolarization consists of two components: the opening of additional Ca-channels not blocked by Co2+ in the presynaptic membrane, and the voltage-dependence of Co2+ blockade. The latter component can explain such a paradoxical phenomenon as an increase of the horizontal cell response to moderate light stimuli when synaptic transmission is partly blocked by Co2+ ions.