The neuronal basis of a sensory analyser, the acridid movement detector system. II. response decrement, convergence, and the nature of the excitatory afferents to the fan-like dendrites of the LGMD.

No dendritic spikes occur in the input fan of the lobular giant movement detector (LGMD) neurone. The action potentials are initiated at the point of thickening of the axon, which therefore represents the site of convergence of the retinotopic projection in the MD system. Previous work has shown that the site of decrement in response to repetitive visual stimulation is distal to this point. No change in spiking threshold in the LGMD could be demonstrated, and decrement in the number of LGMD action potentials is completely explained by the observed decrement of EPSPs recorded in the LGMD input dendritic fan. Possible postsynaptic mechanisms which might affect EPSP amplitude are excluded experimentally or shown to be improbable. Latency measurements during electrical stimulation in the second chiasma (which produces a decrementing EPSP in the fan) indicate that the pathway from the chiasma afferents to the LGMD fan is probably monosynaptic. By exclusion, the site of decrement appears to be located at the presynaptic terminal of that synapse. Generalization of habituation of the response to ON and OFF stimuli is demonstrated, showing that the presynaptic neurone at the labile synapse is an ON/OFF unit. The greater part of the previously described sensitivity gradient on the retina, relative to the MD response, appears to be explicable by the geometry of the LGMD fan and of the retinotopic projection. We conclude that the LGMD is fed by a homogeneous population of ON/OFF units running in the second optic chiasma, which form labile synapses on the input fan.     

The effects of stimulus area and intensity on the on/off ratio of some locust visual interneurones

The on- and off-discharges of three types of locust visual interneurones were recorded in response to luminous discs ranging in subtense from 0.4 to 25°. For the DCMD neurone there was a clear reciprocal relationship between ON and OFF, with large on- and small off-responses at 0.4°, and the reverse at 25° disc subtense. Most of the changeover from almost pure ON to almost pure OFF discharges occurred in the subtense range up to 2°, i.e. within the acceptance angle of one ommatidium or the angle between adjacent ommatidia. This behaviour was not found at low luminance levels, where ON and OFF followed parallel courses. These findings suggest the existence of strong inhibition, augmenting rapidly with increase in target subtense, as also with luminance as shown in separate experiments. For the DCMD the off-response had the characteristics of a simple rebound excitation, following a short period of light exposure.The other visual interneurones (M and S) behaved differently. They did not show reciprocity of ON and OFF, but instead their responses followed parallel courses with increase in subtense, resembling those of the DCMD at low luminance. Nonetheless, like the DCMD, they did show peaking of the on-response at certain subtenses and luminance, although at much higher levels. The inhibitory activity defining the responses of M and S neurones appeared much less effective than that associated with the DCMD. This could be due to greater complexity in their central connexions, of which nothing is known.     

研究: 外膝状体神经元的亮度反应与感受野ON-OFF反应的关系

外膝体是视觉信息进入新皮层的主要通路,其编码亮度信息的神经机制还不清楚.我们采用随机呈现的连续快速变化(50 Hz)的均匀亮度刺激,显著地提高了猫外膝体神经元对均匀亮度的反应强度,通过反相关算法抽提出神经元的亮度反应函数.约81%的神经元的亮度反应函数为单调性上升或下降,有19%的神经元亮度反应函数为V型.通过分析这些神经元对亮度上升和下降的反应强度与感受野ON和OFF反应强度的关系,表明83%的神经元对亮度的反应模式是由其感受野ON-OFF反应的相对强度决定的,其余17%则与其感受野ON-OFF区的兴奋和抑制的变化相关.这些结果揭示了外膝体神经元编码亮度变化的机制.     

Neural adaptation facilitates oscillatory responses to static inputs in a recurrent network of ON and OFF cells

We investigate the role of adaptation in a neural field model, composed of ON and OFF cells, with delayed all-to-all recurrent connections. As external spatially profiled inputs drive the network, ON cells receive inputs directly, while OFF cells receive an inverted image of the original signals. Via global and delayed inhibitory connections, these signals can cause the system to enter states of sustained oscillatory activity. We perform a bifurcation analysis of our model to elucidate how neural adaptation influences the ability of the network to exhibit oscillatory activity. We show that slow adaptation encourages input-induced rhythmic states by decreasing the Andronov–Hopf bifurcation threshold. We further determine how the feedback and adaptation together shape the resonant properties of the ON and OFF cell network and how this affects the response to time-periodic input. By introducing an additional frequency in the system, adaptation alters the resonance frequency by shifting the peaks where the response is maximal. We support these results with numerical experiments of the neural field model. Although developed in the context of the circuitry of the electric sense, these results are applicable to any network of spontaneously firing cells with global inhibitory feedback to themselves, in which a fraction of these cells receive external input directly, while the remaining ones receive an inverted version of this input via feedforward di-synaptic inhibition. Thus the results are relevant beyond the many sensory systems where ON and OFF cells are usually identified, and provide the backbone for understanding dynamical network effects of lateral connections and various forms of ON/OFF responses.     

Electrophysiological evidence for push-pull interactions in the inner retina of turtle

The responses of the inner retinal neurons of turtle to light spots of sizes were studied in an attempt to reveal characteristics that may reflect possible interactions of the neural circuits underlying the center and surround responses. For the ON-OFF cells, the responses were also analyzed to observe whether interference or augmentation of these responses occur. The intracellular recordings revealed several such interactions, observed either in the form of altered spike activity or as changes in the transiency of the light responses. The ON-responding amacrine cell presented in this study became more sustained, while for the ON-OFF amacrine cells larger light spots tended to make the responses more transient and both the ON and OFF components became more pronounced. The spiking activity of the OFF-type ganglion cell shifted in relation to the light stimulus and the number of spikes observed upon presentation of larger spots increased. We suggest that the surround circuits activated by increasing light spots may substantially influence and reorganize not only the overall center-surround balance, but also the center response of the cells. Although it cannot be excluded that intrinsic membrane properties also influence these processes to some extent, it is more likely that lateral inhibition and disinhibitory mechanisms play the leading role in this process.     

Responses of recurrent nets of asymmetric ON and OFF cells

A neural field model of ON and OFF cells with all-to-all inhibitory feedback is investigated. External spatiotemporal stimuli drive the ON and OFF cells with, respectively, direct and inverted polarity. The dynamic differences between networks built of ON and OFF cells (“ON/OFF”) and those having only ON cells (“ON/ON”) are described for the general case where ON and OFF cells can have different spontaneous firing rates; this asymmetric case is generic. Neural responses to nonhomogeneous static and time-periodic inputs are analyzed in regimes close to and away from self-oscillation. Static stimuli can cause oscillatory behavior for certain asymmetry levels. Time-periodic stimuli expose dynamical differences between ON/OFF and ON/ON nets. Outside the stimulated region, we show that ON/OFF nets exhibit frequency doubling, while ON/ON nets cannot. On the other hand, ON/ON networks show antiphase responses between stimulated and unstimulated regions, an effect that does not rely on specific receptive field circuitry. An analysis of the resonance properties of both net types reveals that ON/OFF nets exhibit larger response amplitude. Numerical simulations of the neural field models agree with theoretical predictions for localized static and time-periodic forcing. This is also the case for simulations of a network of noisy integrate-and-fire neurons. We finally discuss the application of the model to the electrosensory system and to frequency-doubling effects in retina.     

Control of Retinal Sensitivity : III. Lateral Interactions at the Inner Plexiform Layer

Both the "on" and the "on-off" ganglion cells in the mudpuppy retina generate graded responses over a narrow range of log test intensities. Sustained full field or surround backgrounds change the range of center log test intensities that elicits the graded response for both cell types. The on-off, but not the on ganglion cells are further affected by moving or flashing surround backgrounds. These cells are hyperpolarized, threshold is elevated, and the entire graded range of response is elicited by a higher range of log center test intensities. Depolarizing activity is elicited in amacrine cells by moving backgrounds that affect the on-off ganglion cells, but bipolar activity is unaffected. These results suggest that the amacrine cells at the inner plexiform layer mediate a third stage of sensitivity control in the retina, increasing threshold for response to change specifically in the on-off ganglion cells.     

Personal digital assistant (PDA) cell phone units produce elevated extremely-low frequency electromagnetic field emissions

Initial tests indicate that personal and occupational use of personal digital assistants (PDAs or palm-held wireless units) produce high intensity bursts of extremely-low frequency electromagnetic fields (ELF-EMF). These emissions could result in comparatively high ELF-EMF exposure in persons that carry a PDA close to the body (i.e., in a pocket or on a belt); or held to the head for cell phone conversations. ELF-EMF emissions of 10 microT were recorded on PDAs during normal office use over a 24 h test period. Results of ELF-EMF measurements show that email transmit and receive functions produce rapid, short-duration ELF-EMF spikes in the 2-10 microT range, each lasting several seconds to over a minute apparently depending on file download size. Some units produced spikes as high as 30-60 microT during email activities. Cell phone activity on PDAs produced continuously elevated ELF-EMF readings in the 0.5-1 microT range, as opposed to the rapid spiking pattern for email receipt and transmission. Switching the PDA unit from "OFF" to "ON" position resulted in single ELF-EMF pulses of over 90 microT on two units. Email downloads into the PDA can occur randomly throughout the day and night when the unit is "ON"; thus the user who wears the PDA may be receiving high-intensity ELF-EMF pulses throughout the day and night. The frequency of email traffic on the PDA, and the power switching unit (battery unit) may affect the frequency and intensity of ELF-EMF emissions.     

High glucose levels impact visual response properties of retinal ganglion cells in C57 mice—An <Emphasis Type="Italic">in vitro</Emphasis> physiological study

This study investigated visual response properties of retinal ganglion cells (RGCs) under high glucose levels. Extracellular single-unit responses of RGCs from mouse retinas were recorded. And the eyecup was prepared as a flat mount in a recording chamber and superfused with Ames medium. The averaged RF size of the ON RGCs (34.1±2.9, n=14) was significantly smaller than the OFF RGCs under the HG (49.3±0.3, n=12) (P<0.0001) conditions. The same reduction pattern was also observed in the osmotic control group (HM) between ON and OFF RGCs (P<0.0001). The averaged luminance threshold (LT) of ON RGCs increased significantly under HG or HM (HG: P<0.0001; HM: P<0.0002). OFF RGCs exhibited a similar response pattern under the same conditions (HG: P<0.01; HM: P<0.0002). The averaged contrast gain of ON cells was significantly lower than that of OFF cells with the HM treatment (P<0.015, unpaired Student’s t test). The averaged contrast gain of ON cells was significantly higher than OFF cells with the HG treatment (P<0.0001). The present results suggest that HG reduced receptive field center size, suppressed luminance threshold, and attenuated contrast gain of RGCs. The impact of HG on ON and OFF RGCs may be mediated via different mechanisms.     

T cells undergo rapid ON/OFF but not ON/OFF/ON cycling of cytokine production in response to antigen

Inflammatory cytokines such as IFN-gamma and TNF produced by Ag-stimulated CD4(+) and CD8(+) T cells are important in defense against microbial infection. However, production of these cytokines must be tightly regulated to prevent immunopathology. Previous studies, conducted with BALB/c mice, have suggested that 1) CD8(+) T cells maintain IFN-gamma production but transiently produce TNF in the continued presence of Ag and 2) lymphocytic choriomeningitis virus-specific and in vitro-propagated effector CD8(+) T cells could rapidly cycle IFN-gamma production ON/OFF/ON in response to Ag exposure, removal, and re-exposure. In contrast with CD8(+) T cells, our results show that Listeria monocytogenes-specific CD4(+) T cells from C57BL/6 mice rapidly initiate (ON cycling) and maintain production of both IFN-gamma and TNF in the continued presence of Ag. Upon Ag removal, production of both cytokines rapidly ceases (OFF cycling). However, if the initial stimulation was maximal, Ag-specific CD4(+) T cells were unable to reinitiate cytokine production after a second Ag exposure. Furthermore, L. monocytogenes-specific CD8(+) T cells in the same mice and lymphocytic choriomeningitis virus-specific CD8(+) T cells in BALB/c mice also underwent ON/OFF cycling, but if the initial Ag stimulus was maximal, they could not produce IFN-gamma after Ag re-exposure. As the initial Ag dose was reduced, the number of cells producing cytokine in response to the second Ag exposure exhibited a corresponding increase. However, T cells that were marked for IFN-gamma secretion during the first stimulation did not contribute cytokine production during the second stimulation. Thus, T cells are not able to undergo rapid ON/OFF/ON cytokine cycling in vitro in response to Ag.     

Response dynamics of bullfrog ON-OFF RGCs to different stimulus durations

Stimulus duration is an important feature of visual stimulation. In the present study, response properties of bullfrog ON-OFF retinal ganglion cells (RGCs) in exposure to different visual stimulus durations were studied. By using a multi-electrode recording system, spike discharges from ON-OFF RGCs were simultaneously recorded, and the cells’ ON and OFF responses were analyzed. It was found that the ON response characteristics, including response latency, spike count, as well as correlated activity and relative latency between pair-wise cells, were modulated by different light OFF intervals, while the OFF response characteristics were modulated by different light ON durations. Stimulus information carried by the ON and OFF responses was then analyzed, and it was found that information about different light ON durations was more carried by transient OFF response, whereas information about different light OFF intervals were more carried by transient ON response. Meanwhile, more than 80 % information about stimulus durations was carried by firing rate. These results suggest that ON-OFF RGCs are sensitive to different stimulus durations, and they can efficiently encode the information about visual stimulus duration by firing rate.     

Analysis of synaptic inputs to on-off amacrine cells of the carp retina

To elucidate the synaptic transmission between bipolar cells and amacrine cells, the effect of polarization of a bipolar cell on an amacrine cell was examined by simultaneous intracellular recordings from both cells in the isolated carp retina. When either an ON or OFF bipolar cell was depolarized by an extrinsic current step, an ON-OFF amacrine cell was transiently depolarized at the onset of the current but no sustained polarization during the current was detected. The current hyperpolarizing the OFF bipolar cell also produced the transient depolarization of the amacrine cell at the termination of the current. These responses had a latency of approximately 10 ms. The amplitude of the current-evoked responses changed gradually with current intensity within the range used in these experiments. They were affected by polarization of the amacrine cell membrane; the amplitude of the current-evoked responses as well as the light-evoked responses was increased when the amacrine cell membrane was hyperpolarized, while the amplitude was decreased when the cell was depolarized. These results confirm directly that ON-OFF amacrine cells receive excitatory inputs from both ON and OFF bipolar cells: the ON transient is due to inputs from ON bipolar cells, and the OFF transient to inputs from OFF bipolar cells. The steady polarization of bipolar cells is converted into transient signals during the synaptic process.     

Pharmacology of the skate electroretinogram indicates independent ON and OFF bipolar cell pathways

Organization of afferent information into parallel ON and OFF pathways is a critical feature of the vertebrate visual system. All afferent visual information in the vertebrate retina reaches the inner plexiform layer (IPL) via bipolar cells. It is at the bipolar cell level that separation of ON and OFF information first appears for afferent information from cones. This may also hold true for the rod pathway of cold-blooded vertebrates, but not for mammals. The all-rod retina of the skate presents an opportunity to examine such pathways in a retina having but a single class of photoreceptor. Immunocytochemical evidence suggests that both ON and OFF bipolar cells are present in the skate retina. We examined the pharmacology of the skate electroretinogram (ERG) to test the hypothesis that independent ON and OFF bipolar cell pathways are functional as rod afferent pathways from outer to inner plexiform layer in the skate. 100 microM 2-amino-4-phosphonobutyric acid (APB) reversibly blocked the skate ERG b-wave. A small d-wave-like OFF component of the ERG revealed by DC recording of response to a prolonged (10 s) flash of light was reduced or blocked by 5 mM kynurenic acid (KYN). We found that addition of 200 microM picrotoxin to the Ringer''s solution revealed prominent ON and OFF components of the skate ERG while reducing the c-wave. These ON and OFF components were reversibly blocked by 100 microM APB and 5 mM KYN, respectively. Reversible block of the OFF component by KYN was also accomplished in the presence of 500 microM N-methyl-DL-aspartate. From these findings, we conclude that ON and OFF bipolar cells are likely to be functional as parallel afferent interplexiform pathways in the all-rod retina of the skate.     

Slow charge movement in mammalian skeletal muscle

Voltage-dependent charge movements were measured in the rat omohyoid muscle with the three-microelectrode voltage-clamp technique. Contraction was abolished with hypertonic sucrose. The standard (ON-OFF) protocol for eliciting charge movements was to depolarize the fiber from -90 mV to a variable test potential (V) and then repolarize the fiber to -90 mV. The quantity of charge moved saturated at test potentials of approximately 0 mV. The steady state dependence of the amount of charge that moves as a function of test potential could be well fitted by the Boltzmann relation: Q = Qmax/(1 + exp[-(V - V)/k]), where Qmax is the maximum charge that can be moved, V is the potential at which half the charge moves, and k is a constant. At 15 degrees C, these values were Qmax = 28.5 nC/microF, V = -34.2 mV, and k = 8.7 mV. Qmax, k, and V exhibited little temperature dependence over the range 7-25 degrees C. "Stepped OFF" charge movements were elicited by depolarizing the fiber from -90 mV to a fixed conditioning level that moved nearly all the mobile charge (0 mV), and then repolarizing the fiber to varying test potentials. The sum of the charge that moved when the fiber was depolarized directly from -90 mV to a given test potential and the stepped OFF charge that moved when the fiber was repolarized to the same test potential had at all test potentials a value close to Qmax for that fiber. In nearly all cases, the decay phase of ON, OFF, and stepped OFF charge movements could be well fitted with a single exponential. The time constant, tau decay, for an ON charge movement at a given test potential was comparable to tau decay for a stepped OFF charge movement at the same test potential. Tau decay had a bell-shaped dependence on membrane potential: it was slowest at a potential near V (the midpoint of the steady state charge distribution) and became symmetrically faster on either side of this potential. Raising the temperature from 7 to 15 degrees C caused tau decay to become faster by about the same proportion at all potentials, with a Q10 averaging 2.16. Raising the temperature from 15 to 25 degrees C caused tau decay to become faster at potentials near V, but not at potentials farther away.(ABSTRACT TRUNCATED AT 400 WORDS)     

Two-photon imaging reveals somatodendritic chloride gradient in retinal ON-type bipolar cells expressing the biosensor Clomeleon

A somatodendritic gradient of Cl(-) concentration ([Cl(-)](i)) has been postulated to generate GABA-evoked responses of different polarity in retinal bipolar cells, hyperpolarizing in OFF cells with low dendritic [Cl(-)](i), and depolarizing in ON cells with high dendritic [Cl(-)](i). As glutamate released by the photoreceptors depolarizes OFF cells and hyperpolarizes ON cells, the bipolars' antagonistic receptive field (RF) could be computed by simply integrating glutamatergic inputs from the RF center and GABAergic inputs from horizontal cells in the RF surround. Using ratiometric two-photon imaging of Clomeleon, a Cl(-) indicator transgenically expressed in ON bipolar cells, we found that dendritic [Cl(-)](i) exceeds somatic [Cl(-)](i) by up to 20 mM and that GABA application can lead to Cl(-) efflux (depolarization) in these dendrites. Blockers of Cl(-) transporters reduced the somatodendritic [Cl(-)](i) gradient. Hence, our results support the idea that ON bipolar cells employ a somatodendritic [Cl(-)](i) gradient to invert GABAergic horizontal cell input.     

The functional organization of the crayfish lamina ganglionaris

The light responses of the second order lamina monopolar neurons were examined in the crayfish compound eye. Single cartridge monopolar neurons (M1-M4) exhibited nonspiking hyperpolarizing light responses; for M1, M3 and M4 the transient 'on' response operated over the same intensity range as the receptor, 3.5 log units. M2 operated in a much narrower intensity range (1.5 log unit). The 'on' responses were associated with a 19% increase in conductance. The hyperpolarizing 'on' response can be reversed at 18 mV below the resting membrane potential. The half-angular sensitivity width of monopolar cells (in partially dark-adapted eyes) is 15 degrees X 8 degrees (horizontal by vertical). Off axis stimuli elicit attenuated hyperpolarizing responses associated with a diminished conductance increase or depolarizing responses associated with a net decrease in conductance. The latter result is consistent with the presynaptic inhibition of a 'back-ground' transmitter release which normally persists in the dark. Lateral inhibition is elicited from the area immediately surrounding the excitatory field, and it is associated with diminished transient responses and an accelerated decay of the response. Inhibitory stimuli decrease the conductance change associated with the hyperpolarizing response. The surround stimuli can also elicit depolarizing 'off' responses with reversal potentials positive to the membrane resting potential. It is concluded that the rapidly repolarizing monopolar cell response is modulated by both pre- and postsynaptic inhibitory mechanisms. A compartment model indicates that signal attenuation along a 500 microns length of monopolar cell axon is 22-34%. Simulation of steady-state signal transmission suggests that passive (decremental) conduction is sufficient to convey 66 to 78% of the monopolar cell signal from lamina to medulla. The current-voltage relation in current clamp is linear over the physiological operating range, and there is no evidence for rectification. Hyperpolarization of single monopolar cells (M1-M4) provides a polysynaptic excitatory signal to the medullary sustaining fibers.     

Visual stimulation is required for refinement of ON and OFF pathways in postnatal retina

ON and OFF pathways separately relay increment and decrement luminance signals from retinal bipolar cells to cortex. ON-OFF retinal ganglion cells (RGCs) are activated via synaptic inputs onto bistratified dendrites localized in the ON and OFF regions of the inner plexiform layer. Postnatal maturational processes convert bistratifying ON-OFF RGCs to monostratifying ON and OFF RGCs. Although visual deprivation influences refinement of higher visual centers, no previous studies suggest that light regulates either the development of the visual-evoked signaling in retinal ON and OFF pathways, nor pruning of bistratified RGC dendrites. We find that dark rearing blocks both the maturational loss of ON-OFF responsive RGCs and the pruning of dendrites. Thus, in retina, there is a previously unrecognized, pathway-specific maturation that is profoundly affected by visual deprivation.     

Kinetics of intramembrane charge movement and conductance activation of batrachotoxin-modified sodium channels in frog node of Ranvier

Sodium current and intramembrane gating charge movement (Q) were monitored in voltage-clamped frog node of Ranvier after modification of all sodium channels by batrachotoxin (BTX). Sodium current activation followed a single-exponential time course, provided a delay was interposed between the onset of the step ON depolarization and that of the current change. The delay decreased with increased ON depolarization and, for a constant ON depolarization, increased with prehyperpolarization. ON charge movement followed a single-exponential time course with time constants tau Q,ON slightly larger than tau Na, ON. For pulses between -70 and -50 mV, tau Q,ON/tau Na,ON = 1.14 +/- 0.08. The OFF charge movement and OFF sodium current tails after a depolarizing pulse followed single-exponential time courses, with tau Q, OFF larger than tau Na, OFF. tau Q,OFF/tau Na,OFF increased with OFF voltage from 1 near -100 mV to 2 near -160 mV. At a set OFF potential (-120 mV), both tau Q,OFF and tau Na,OFF increased with ON pulse duration. The delay in INa activation and the effect of ON pulse duration on tau Q,OFF and tau Na,OFF are inconsistent with a simple two-state, single-transition model for the gating of batrachotoxin-modified sodium channels.     

Blocking Retinal Chloride Co-Transporters KCC2 and NKCC: Impact on Direction Selective ON and OFF Responses in the Rat's Nucleus of the Optic Tract

In the present study we investigated in vivo the effects of pharmacological manipulation of retinal processing on the response properties of direction selective retinal slip cells in the nucleus of the optic tract and dorsal terminal nucleus (NOT-DTN), the key visuomotor interface in the pathway underlying the optokinetic reflex. Employing a moving visual stimulus consisting of either a large dark or light edge we could differentiate direction selective ON and OFF responses in retinal slip cells. To disclose the origin of the retinal slip cells' unexpected OFF response we selectively blocked the retinal ON channels and inactivated the visual cortex by cooling. Cortical cooling had no effect on the direction selectivity of the ON or the OFF response in NOT-DTN retinal slip cells. Blockade of the retinal ON channel with APB led to a loss of the ON and, to a lesser degree, of the OFF response and a reduction in direction selectivity. Subsequent blocking of GABA receptors in the retina with picrotoxin unmasked a vigorous albeit direction unselective OFF response in the NOT-DTN. Disturbing the retinal chloride homeostasis by intraocular injections of bumetanide or furosemide led to a loss of direction selectivity in both the NOT-DTN's ON and the OFF response due to a reduced response in the neuron's preferred direction under bumetanide as well as under furosemide and a slightly increased response in the null direction under bumetanide. Our results indicate that the direction specificity of retinal slip cells in the NOT-DTN of the rat strongly depends on direction selective retinal input which depends on intraretinal chloride homeostasis. On top of the well established input from ON center direction selective ganglion cells we could demonstrate an equally effective input from the retinal OFF system to the NOT-DTN.