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.

[Electrical feedback in the chemical synapses]. / Elektricheskaia obratnaia sviaz' v khimicheskikh sinapsakh.

Electrical feedback in chemical synapses and the efficacy of synaptic transmission grow with the increase in the gap resistance, so they should be higher in invaginated synapses than in the flat ones. So the plastic changes in the invagination depth may provide a morphological basis for long-term changes in synaptic efficacy: long-term potentiation (LTP) in brain and retinal synapses. In retinal photoreceptor triad synapses, the electrical feedback can provide an "operational" (instantaneous) control of synaptic transmission.

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.

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.

Low-calcium-induced enhancement of chemical synaptic transmission from photoreceptors to horizontal cells in the vertebrate retina.

According to the classical calcium hypothesis of synaptic transmission, the release of neurotransmitter from presynaptic terminals occurs through an exocytotic process triggered by depolarization-induced presynaptic calcium influx. However, evidence has been accumulating in the last two decades indicating that, in many preparations, synaptic transmitter release can persist or even increase when calcium is omitted from the perfusing saline, leading to the notion of a "calcium-independent release" mechanism. Our study shows that the enhancement of synaptic transmission between photoreceptors and horizontal cells of the vertebrate retina induced by low-calcium media is caused by an increase of calcium influx into presynaptic terminals. This paradoxical effect is accounted for by modifications of surface potential on the photoreceptor membrane. Since lowering extracellular calcium concentration may likewise enhance calcium influx into other nerve cells, other experimental observations of "calcium-independent" release may be reaccommodated within the framework of the classical calcium hypothesis without invoking unconventional processes.

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.

[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.

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.

[Effect of changes in blood glucose concentration on the standing potential of the rabbit eye]. / Vliianie izmenenii kontsentratsii gliukozy v krovi na postoiannyi potentsial glaza krolika.

The paper deals with the study of the influence of changes of glucose blood concentration in rabbits on the standing potential of the eye, which reflects the functioning of the retinal pigment epithelium and photoreceptors. Recordings of the electrooculogram (EOG), determination of glucose blood level and ophthalmoscopic and histological examinations of the eye were performed in 48 rabbits. Short-term increase of glucose concentration was accompanied by the increase in the standing potential and Arden EOG ratio, with hypoglycemia evoking the opposite effect. A long-term (4 month) hyperglycemia was accompanied by the reversible decrease of both parameters studied. No ophthalmoscopic and histological changes were observed.

[Local nonuniformities in the syncytium of the horizontal cells of the retina in the turtle]. / Lokal'nye neodnorodnosti sintsitiia gorizontal'nykh kletok setchatki cherepakhi.

Electrical coupling between horizontal cells of the turtle retina was investigated by means of two microelectrodes (current and recording ones) penetrating neighbouring cells at a fixed distance from each other. The morphological coupling was revealed by means of fluorescent dye Lucifer Yellow. The electrical coupling was confirmed between elements of similar type (L1--axonal terminals, or L2--cell bodies, or R/G type cells) and no coupling was found between elements of different types, though L1 and L2 are directly connected through thin axons. In the L1 syncytium the electrical coupling at small (less than or equal to 50 microns) but fixed distances between microelectrodes could differ several times depending on the minimal displacement of microelectrodes. This local nonuniformity of coupling can be explained on the basis of structural nonuniformities in the L1 (axon terminal) network. It is unlikely however that the structural nonuniformities can influence the functional properties of horizontal cell network when the retina is stimulated adequately (by light).

[Intracellular recording of potentials of cells of isolated cerebellum in the frog]. / Vnutrikletochnoe otvedenie potentsialov kletok izolirovannogo mozzhechka liagushki.

Intracellular potentials of granular, Purkinje and glial cells were recorded in an isolated frog cerebellum in response to electrical stimulation of cerebellar peduncle. The stimuli inhibited strongly the activity of most granular cells. "Slow" (20-50 ms) and "fast" (1-2 ms) spikes were recorded in Purkinje cells. Glial cell responses consisted of a slow waves of depolarization summated with repetitive stimuli and reached an amplitude of 20 mV.

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 response of frog lingual epithelium to stimulation of the gustatory nerve]. / Elektricheskaia reaktsiia épiteliia iazyka liagushki na razdrazhenie vkusovogo nerva.

Electrical stimulation of the gustatory nerve evoked a positive electrical response of the outer surface of the tongue (relative to its inner layers). The amplitude and the rate of rise of the response grew and the latency fell with increased frequency of stimulation. The response originated in the superficial epithelial layer (30-60 micrometers) and was produced by a decrease of "resting potential" (negative-outside) of this layer. The response was accompanied by a strong decrease of the superficial tongue layer resistance and arose probably as a result of short-circuiting of the epithelial layer by high-conductive nonspecific channels. Similar response accompanied by a decrease of the superficial tongue layer resistance was recorded with adequate stimulation (by acetic acid vapours). The results are compared with the response of the frog skin to the stimulation of cutaneous nerve.

[Ionic metabolism in the horizontal cells of the retina]. / Osobennosti ionnogo obmena v gorizontal'nykh kletkakh setchatki.

According to the experimental data, the membrane potential of L-type horizontal cells in the bright light (i.e. when the input synapses are completely closed) is close to the potassium equilibrium potential. Basing on this fact the intracellular concentrations of K+ and Na+ ions are estimated. The latter proved to be relatively high (several tens mM) and comparable with intracellular concentration of potassium ions. This result in combination with the proximity of the light response equilibrium potential to zero level demonstrates that not only sodium conductance of a synaptic membrane but also potassium one take part in generation of light response. It is shown that stationary sodium and potassium synaptic currents are relatively weak and their variation within a working range of the membrane potentials (from -72 to -16 mV) is rather small. This stabilization of synaptic currents results from nonlinear properties of a nonsynaptic membrane of horizontal cells.

[Ionic mechanisms of the nonlinearity of retinal horizontal cell membranes]. / Ionnye mekhanizmy nelineinosti membrany gorizontal 'nykh kletok setchatki.

Changes in ionic conductivity underlying the nonlinearity a voltage-current curve of the nonsynaptic membrane of horizontal cells were investigated in experiment on goldfish and turtle retina. The measurements were made under conditions when conductivity of a subsynaptic membrane was minimal, i.e. when the retina was illuminated with bright light or synaptic transmission from photoreceptors was blocked with Co2+. An increase in [K+] led to depolarization and diminution os steepness i a hyperpolarizing part of the voltage-current curve; a decrease in K+ evoked an opposite effect. A decrease in [C1-] did not change both the membrane potential and the shape of the voltage-current curve. Substitution of Na+ by tris or choline did not evoke a reliable change in the membrane potential, and produce only a slight change in the shape of he current-voltage curve. It is concluded that the membrane is permeable for K+; permeability for C1- is absent or small; permeability for Na + is small too. Ba2+ (2-5 mM) increased the steepness of the hyperpolarizing part of the voltage current curve, and the curve became more linear. It is concluded that the nonlinearity is determined mainly by potential-dependent k+-channels whose conductivity increases with hyperpolarization, and Ba2+ blocks this increase in permeability. An increase in Ca2+ from 1 to 20 mM enhanced the steepness of the depolarizing part of the voltage-current curved without altering the hyperpolarizing part. It is supposed that the horizontal cell membrane has potential-dependent Ca2+- channels whose conductivity increases with depolarization.

[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.