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Ichinose, T. Roles of on cone bipolar cell subtypes in temporal coding in the mouse retina. Download references. E and T. You can also search for this author in PubMed Google Scholar.
Correspondence to Thomas Euler. This term describes bipolar cells that send projections to two strata within the retina's inner plexiform layer. This term describes bipolar cells that send projections to three strata within the retina's inner plexiform layer. Light-sensitive G protein-coupled receptors that are expressed in photoreceptors. Different opsin types are sensitive to different wavelengths of light, and thus comparing the responses of spectrally distinct types forms the basis of colour vision.
In addition to rhodopsin, the opsin of the rod photoreceptors, mammals express up to three types of cone opsins: short-, mid- and long-wavelength-sensitive opsins. This term is used here to describe a single neuronal compartment that does not exhibit local voltage differences. A stochastic process that counts the number of events and their timing. Inter-arrival times between each pair of consecutive events have an exponential distribution and are independent.
A simplified model of neural responses to an arbitrary stimulus that is based on a sequential set-up of a linear operation followed by a non-linear operation. Specialized presynaptic structures found in some sensory neurons — including bipolar cells and photoreceptors — that promote the trafficking and fusion of synaptic vesicles at the active zone. This term is used to denote the idea that a single neuron may relay different synaptic signals to different postsynaptic partners.
Reprints and Permissions. Retinal bipolar cells: elementary building blocks of vision. Nat Rev Neurosci 15, — Download citation. Published : 18 July Issue Date : August Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.
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Skip to main content Thank you for visiting nature. Subjects Colour vision Retina. Key Points Bipolar cells are the only neurons that connect the outer retina to the inner retina. Abstract Retinal bipolar cells are the first 'projection neurons' of the vertebrate visual system — all of the information needed for vision is relayed by this intraretinal connection.
Access through your institution. Buy or subscribe. Rent or Buy article Get time limited or full article access on ReadCube. Figure 1: Organization of the bipolar cells in a mammalian retina. Figure 2: Bipolar cell anatomy. Figure 3: Shaping bipolar cell signals: dendrites and axon terminals.
Figure 4: Building ganglion cell circuits from bipolar cell elementary operations. References 1 Dreosti, E. Google Scholar 9 Lin, B. Google Scholar 17 Euler, T. Google Scholar 76 Nathans, J. Google Scholar 84 Kryger, Z.
Google Scholar Sun, W. View author publications. Ethics declarations Competing interests The authors declare no competing financial interests.
Supplementary information. Supplementary information S1 figure Organization of the bipolar cell types in the mouse retina. PDF kb. Supplementary information S2 table Immunomarkers and transgenic lines for mouse bipolar cells PDF kb. PowerPoint slides PowerPoint slide for Fig. PowerPoint slide for Fig. Last update: 3 April Record number: Veuillez activer JavaScript. Por favor, active JavaScript.
Bitte aktivieren Sie JavaScript. Si prega di abilitare JavaScript. In the eye of the observer: Visual processing at the heart of the retina. Results in Brief. But the centre and the surrounding area of each circle work in opposite ways: a ray of light that strikes the centre of the field has the opposite effect from one that strikes the area surrounding it known as the "surround". In fact, there are two types of bipolar cells, distinguished by the way they respond to light on the centres of their receptive fields.
If a light stimulus applied to the centre of a bipolar cells's receptive field has an excitatory effect on that cell, causing it to become depolarized, it is an ON-centre cell. A ray of light that falls only on the surround, however, will have the opposite effect on such a cell, inhibiting hyperpolarizing it. The other kind of bipolar cells, OFF-centre cells, display exactly the reverse behaviour: light on the field's centre has an inhibitory hyperpolarizing effect, while light on the surround has an excitatory depolarizing effect.
Just like bipolar cells, ganglion cells have concentric receptive fields with a centre-surround antagonism. But contrary to the two types of bipolar cells, ON-centre ganglion cells and OFF-centre ganglion cells do not respond by depolarizing or hyperpolarizing, but rather by increasing or decreasing the frequency with which they discharge action potentials.
That said, the response to the stimulation of the centre of the receptive field is always inhibited by the stimulation of the surround. The receptive fields of the neurons of the primary visual cortex are not circular, but rectangular. They respond especially well to rays of light that are oriented in a particular direction.
The cells whose receptive fields thus respond to light with a specific orientation are called simple cells. These rectangular receptive fields often have an ON centre band that responds positively to light flanked by two OFF side bands that respond to darkness.
The diagram here shows that when the beam of light is not oriented to follow the ON band precisely, the stimulus is simply not effective for this cell.
The simple cell receptive fields in the primary visual cortex are thought to be the result of the convergence of several adjacent receptive fields of cells in the relay that precedes it, the lateral geniculate nucleus.
Inhibitory currents arise mainly from amacrine cells. The illustration is from Pang et al, In rat retina, bipolar cell axon terminal arborization appears to obey perfectly the rule of ON and OFF layering 7. As judged by the level of axonal stratification, there are 9 bipolar types. The axons of cone bipolar cells branch in the outer half of rat IPL sublamina a. Four cone bipolar cell types types with axons branching in the inner half of rat IPL sublamina b were identified.
In net 12 of 14 of cells of these types responded with outward currents to APB, whereas only one responded to kainate 7.
Bipolar cell branching patterns in mouse retina appear similar to rat A more limited set of recordings in cat and monkey retinas suggest also that there may be good adherence to ON and OFF stratification of bipolar terminals , Li and DeVries 15 have provided a significant technical advance in the mapping of form onto function for biplolar cells of the all-cone retina of ground squirrel.
In these studies one patch electrode was used to electrically stimulate an individual cone within the dendritic arbor of a bipolar cell simultaneously patched and stained by a second microelectrode. In this way both the cone contacts and the nature of these contacts onto bipolar cells are directly verified.
Six cone bipolar types have been mapped by this technique, one ON type contacting only blue cones, an ON and an OFF type contacting both blue and green cones, and remaining types contacting only green cones Fig.
No color opponent cone synaptic inputs using different glutamate receptors were detected in ground squirrel bipolar cells. The lamination patterns for ON and OFF types follows that proposed for rod-dominated mammalian retinas , Axonal stratification of bipolar cells in ground squirrel retina. Bipolar cells are stained by dye-filled patch electrodes while recording responses to microelectrode stimulation of individual cones contacting the dendritic tips.
While the cone contacts vary, the ON and OFF stratification of axon terminals follow the typical vertebrate pattern. The illustration is from Li and DeVries, In work still in progress in the Dowling laboratory, cone contact patterns have been added to axonal stratification patterns , , resulting in perhaps 20 or more bipolar types that can be anatomically distinguished. There are 5 exclusively cone-contacting groups that are distinguished by the pattern of cones contacted and by axonal stratification.
There are 4 types that contact rods in addition to various cone groupings Mb types. The most selective cone-contacting type contacts only green-cones. It is very wide in dendritic and axonal field and is OFF-stratified. The most diffuse pattern of photoreceptor contacts is an OFF stratified type that contacts all photoreceptors, rods, red, blue, green, and UV cones. In mammals it appears that all the dendritic contacts emanating from a single bipolar cell express the same glutamate receptor This appears not to be the case in fish or amphibian bipolar cells, where the same cell may express different glutamate receptors at different dendritic tips 72, 82, 88, , with each receptor type segregating according to the photoreceptor type contacted 82, Glutamate responses of zebrafish bipolar cells with axonal boutons in sublamina a Group a and sublamina b Group b are summarized in Fig.
Bipolar cells with 1 or 2 terminal boutons restricted either to sublamina a or to sublamina b obey the ON and OFF stratification rule. ON cells branching in sublamina b express either or both of two inhibitory glutamate mechanisms, ionotropic I glu , transporter-like chloride current or metabotropic APB receptor. ON and OFF stratification of bipolar-cell axon terminals in zebrafish retina. APB shows cells responding to glutamate, APB, or both with outward currents and reversal potentials at or beyond 0 mV.
NMDA evoked no responses. There is an immunoreactive band for glycine gly that appears to separate IPL sublamina a from b. Bisublaminar orderliness breaks down to some extent in species where multistratified bipolar cell axons are common. While multistratified cells exist in mammals like monkeys, cats, and squirrels 10, 15, , Fig. Multistratified types selectively contact cones 19, and so may be characteristic of cone-dominated species.
If broad or multistratified bipolar terminals are restricted to either the ON or the OFF sublaminae i. This is seen for type b3 bipolar cells in ground squirrel Fig. In giant danio such cells are color opponent In zebrafish multistratified bipolar cells with boutons in both sublaminae were found to be either ON or OFF types Fig. The pattern for other giant danio ON bipolar cells is similar to zebrafish where the I glu , or excitatory amino acid transporter EAAT , mechanism is found particularly in ON-type cone contacting bipolar cells, while the mixed Mb rod and cone contacting types utilize both EAAT and MGluR6 mechanisms Rod bipolar cells are unique.
These cells are easily identified in both mammals and fish In most mammals, judged by axonal stratification pattern and contacts with photoreceptors, there is only a single class of rod bipolar cell 20, The axon descends deep into ON sublamina b of the IPL, where it arborizes in a bulbous terminal just adjacent to ganglion cells Fig.
The mammalian rod bipolar cell is an ON-type cell utilizing metabotropic APB-sensitive, glutamate receptors 31, 32, 64, In fish, the comparable cell type is the Mb bipolar cell In fish retinas, rod-contacting bipolar cells also contact cones.
Five such types are found in goldfish retina, including multiple ON types with axon terminals branching in sublamina b , and likely OFF types with axon terminals branching in sublamina a Interestingly in mouse retina there also appear to be multiple ON type rod bipolar cells.
While axon-terminal morphology differs only subtly, light-evoked signals in DBC R1 are completely rod dominated, whereas DBC R2 , similar to fish, receives substantial cone signal input in addition to rod input.
The cone signals in DBC R2 types disappear in connexin 36 knockout mice , Regardless of species, classic ON-center rod bipolar cells are all universally recognized by high immunoreactivity for protein kinase C PKC 64, , , Rod bipolar cells in the mammalian retina are ON type ON rb. The illustration is modified from Kolb and Famiglietti, Although the axon terminals of rod bipolar cells are directly adjacent to ganglion cells, they do not contact them directly.
In the mammalian retina, the AII amacrine cell , , is the first intermediary in transferring rod bipolar signals to ganglion cells. The AII cell achieves this through direct innervations of cone bipolar processes within the IPL, either by means of chemical synapses with OFF bipolar cells large arrow in sublamina a , Fig.
The cone bipolar axon terminals are the second intermediary in transferring rod bipolar signals to ganglion cells. The AII-amacrine-to-cone-bipolar gap junction is down-regulated by the humeral factor nitric oxide acting through an intracellular cGMP pathway and also is susceptible to pharmacological blockade by meclofenamic acid This occurs through two pathways.
In the first, signals flow through gap junctions between rods and cones , and by this pathway into cone bipolar cells. In the second, cone-contacting bipolar cells make direct dendritic contact with rods, as commonly occurs in non-mammals 14, , , In mammals this type of cone bipolar pathway is usually restricted to OFF cone bipolar cell dendritic contacts with rods , , This pathway bypasses the slower, albeit higher gain and more sensitive, metabotropic pathway of rod bipolar cells using the faster ionotropic pathways in the OFF cone bipolar cells In contrast to the typical mammalian pattern, mouse retina shows an analogy to fish retina in having ON cone bipolar cells that directly contact rods Separate rod signaling pathways can be distinguished in humans, both behaviorally, and in evoked potential recordings A sensitive scotopic pathway may represent the rod-bipolar-to-AII pathway, whereas a less sensitive and faster mesopic pathway may represent a rod-to-cone gap-junction pathway, or perhaps additionally, an OFF cone bipolar pathway with direct rod input.
Voltage-gated channels permeate the membranes of retinal bipolar cells and contribute to voltage responses. Intracellular recordings show bipolar cells produce graded potentials in response to a light stimulus, but not action potentials 1. It seems rather that these currents may typically serve to amplify synaptic events and shape photoresponse waveforms.
The cb5b bipolar cell of ground squirrel retina is an exception. The light-evoked bipolar spikes appear to trigger impulse generation in post-synaptic ganglion cells. Spontaneous and light-evoked actions potentials in a ground squirrel bipolar cell. Four traces are superimposed in A. The short horizontal bar represents a 40 msec light flash that evokes a spike doublet at the beginning of each trace. The remaining spikes are spontaneous activity. In D the red label is the neurobiotin NB injected cb5b bipolar cell.
The green label in D and E is a calbindin reactive cb2 OFF bipolar cell, not recorded in this session. The illustration is modified from Saszik and DeVries, 5.
Voltage gated currents found in zebrafish bipolar cells. Inward currents Isust or Ih are evoked by hyperpolarizing voltage blue traces, left.
The illustration is modified from Connaughton and Maguire, In goldfish and tiger salamander retina 25 , a slowly activating, delayed rectifying I K potassium current, modulated by dopamine , is activated. In contrast, axolotl bipolar neurons express a rapidly activating, slowly inactivating I A current in response to depolarizing membrane potentials.
These outward currents tend to hyperpolarize the cell, restoring membrane potential after depolarization. On the other hand membrane hyperpolarizations elicit the slowly activating, inward rectifying I h current , This also tends to restore membrane potential. These were recorded in zebrafish retinal bipolar cells. As described above, light stimulation of the bipolar cell receptive field reveals characteristic center-surround antagonism Fig. It is believed that the center component of the bipolar cell light response arises from direct glutamatergic inputs from photoreceptors, while the surround response is generated indirectly by horizontal-cell suppression of glutamate release from cones Horizontal-cell feedback to cones is further discussed in the Webvision chapter S-potentials and horizontal cells.
Chloride-mediated responses at light onset and offset have been observed in ON bipolar cells of tiger salamander 12, 25, These components appear to originate with AMPA excitation of GABAergic and glycinergic inhibitory interneurons, rather than with photoreceptors directly 25, Rod dominated cells tend to have sustained ON inhibition without offset inhibitory transient, whereas cone dominated cells are transiently inhibited at both onset and offset of the stimulus Immunocytochemical studies show that bipolar-cell dendrites and terminals are surrounded by GABAergic processes.
Illustrations of the GABAergic inhibitory synaptic arrangements surrounding bipolar cell axon terminals appear in figure 21 for a cyprinid Mb rod bipolar terminal and in figure 22 for a cat rod bipolar cell axon terminal. The illustration is from Marc and Liu, This suggests a major inhibitory feedback circuit from neighboring amacrine cells occurs through direct GABAergic input onto bipolar-cell terminals.
GABAergic inputs to bipolar dendrites may also occur indirectly, through a feedback synapse involving photoreceptors GABAergic and glycinergic inhibitory terminals surround a rod bipolar axon terminal RB in cat retina. The AII amacrine cell is known to be glycinergic purple. The electron micrograph is adapted from Kolb, GABA-elicited currents have both transient and sustained components.
The sustained components of GABA C responses last many minutes and the hyperpolarizing action is readily seen in voltage probe studies of dissociated bipolar cells using oxonol, a slow distributive probe, as voltage reporter , With light stimuli these receptors transfer more net charge to bipolar cell terminals than either GABA A or glycine receptors A rod bipolar cell is dissociated from goldfish retina left.
When the selected cellular regions are stimulated with micro puffs of GABA, the most sensitive region is the axon terminal right. The figure is modified from Tachibana and Kaneko, These receptors have been identified on the axon terminals of salamander and goldfish bipolar cells, where they reduce calcium influx , , modulating synaptic release of bipolar-cell glutamate. GABA receptors affect the dynamics of retinal light responses Zhang et al suggest a serial synaptic pathway to explain this counterintuitive result.
In this model a counterintuitive action is explained by a polysnaptic pathway. GABA release from amacrine cells activates receptors on bipolar cell terminals, causing the suppression of a depolarization-elicited calcium current , and associated synaptic release presumably modulating or reducing neurotransmitter release from these cells Measurement of the light evoked excitatory currents in amacrine cells postsynaptic to bipolar cells suggests that the kinetically slower GABA C inhibition limits the duration of excitatory post-synaptic events, whereas the faster glycine and GABA A inhibition limits the peak amplitude of postsynaptic excitatory events When both antagonists are mixed together, the GABA response is fully blocked.
The illustration is from Lukasiewicz and Shields, While being wide in dendritic field, the action of A17 amacrine cells on rod-bipolar axon terminals is local , and depends on calcium entry through local A17 AMPA channels excited by the rod-bipolar-cell ribbon synapse , not impulses propagating in the A17 dendrites GABA C inhibition of rod bipolar terminals is long range and depends on impulse activity These two inhibitory systems have been dissected in the Diamond laboratory.
The short range reciprocal GABA A feedback is eliminated by ablating A17 amacrine cells with 5,7 dihydroxytryptamine DHT , a toxic serotonin analogue that is selectively taken up by A This abolishes nerve spikes that allow signal propagation along amacrine cell dendrites other than A Interestingly, though wide in dendritic field, the regulatory actions of A17 appear to be independent local-circuit reciprocal interactions with rod bipolar cells Fig. Long-range and short-range inhibitory circuits for rod-bipolar-cell axon terminals.
The spatial profiles of GABA inhibitory responses are evaluated by puffing glutamate at different distances. This excites all GABAergic amacrine cells.
DHT-ablated retinas lack local feedback from A17 amacrine cells. TTX treated retinas lack long range feedback. This suggests a lack of interaction between the two systems. The illustration is from Chavez, Grimes and Diamond, Glycine applied to bipolar cells elicits a strychnine-sensitive, hyperpolarizing chloride current.
As with GABA, different bipolar-cell regions are differentially sensitive to glycine. In mouse , and carp the axon terminal shows the greatest sensitivity; while in rat and salamander the dendrites are more sensitive.
There is a tendency for glycinergic inhibitory circuitry to impinge selectively on OFF cone bipolar cells , ; the outstanding example is AII amacrine innervation of the mammalian OFF cone bipolar cells , In this case glycine acts as a neurotransmitter intermediary in the pathway to dark adapted ganglion-cell center responses Fig.
In general the inhibitory pathway onto cone-bipolar-cell axon terminals uses glycine, whereas the rod bipolar axon terminal receives GABAergic inhibition Glycine, however, is a component of inhibition on rod bipolar terminals. Dendritic impulse propagation plays a role in the transmission of glycinergic inhibition at this synapse. Noise analysis performed on glycine-elicited currents from dendrites and axon terminal suggests that each region may express a different subtype of glycine receptor In fish retinas glycinergic inputs to bipolar-cell dendrites and axon terminals are believed to arise directly from populations of amacrine and glycinergic interplexiform cells Glycine-containing interplexiform cells have only been seen so far in fish retinas; glycine receptors can be found on processes postsynaptic to photoreceptors, including bipolar cell dendritic processes Glycine is believed to modulate the surround light responses of bipolar cells, though the reported effects of glycine are not consistent.
Stone and Schutte , working in Xenopus, report that glycine application eliminated surround responses in both ON- and OFF-type bipolar cells. In contrast, surround responses in salamander are not blocked by glycine While GABA application elicits responses in all bipolar cells examined, glycine elicits responses from only a subset of bipolar cells, such as OFF bipolar cells in carp and the small-field bipolar cells in skate , suggesting glycine may have a selective role in retina.
Glycinergic feedback connections between amacrine and bipolar cells decrease light-evoked glutamate release onto ganglion cell dendrites Glycinergic feed-forward synapses transfer rod bipolar signals from AII amacrine cells to OFF cone bipolar terminals in mammalian retinas , Thus, glycinergic synapses onto bipolar cells may be important in mediating the transfer of information among neurons in both the proximal and distal retina. Due to their large size, the axon terminals of goldfish Mb1-type ON-bipolar cells are used as a model system in which to examine neurotransmitter release.
The axon terminal can be directly recorded in patch clamp studies Changes in internal calcium and both exocytosis and endocytosis activity , can be detected using fluorescent calcium probes and observing capacitance changes as vesicle membrane is added or removed from this presynaptic terminal. Images of releasing vesicles at Mb1 terminals are seen by evanescent fluorescence microscopy in figure Vesicle release at Mb-1 bipolar terminals can be observed by evanescent fluorescence microscopy.
Schematic showing simultaneous stimulation of release by patch recording, and dark-field evanescent fluorescence imaging of FM loaded fluorescent vesicles. Single frame showing vesicles near the membrane. The asterisked vesicles were released and disappeared in subsequent frames c and d. Averages of multiple images show preferred sites of vesicle docking and or release circles and arrowheads in c , d.
The actual sites of release during the averaged image are indicated as red dots. The illustration is from Zenesek et al, Neurotransmitter release from bipolar terminals occurs at ribbon synapses , ; conventional synapses are rare in bipolar axon terminals although they have been seen in some species , Each ribbon is an electron dense structure oriented perpendicular to the plasma membrane.
The arrangement of the ribbon synapse at the bipolar cell axon terminal and associated post-synaptic events are shown in figure All vesicles associated with the ribbon constitute the readily releasable pool of vesicles. Species with smaller rod or cone bipolar axon terminals amphibians, reptiles and mammals have smaller numbers of ribbons and smaller volumes to contain synaptic vesicles so the release rates may be different compared with the model goldfish system.
Left , cartoon of a ribbon synapse at a salamander ON bipolar synapse. Docked vesicles, release sites, transporters and postsynaptic receptors are indicated. The illustration is from Miller et al. The ribbon synapse, in the absence of light, releases vesicles spontaneously. The single spontaneous excitatory postsynaptic synaptic currents sEPSCs can be studied by voltage clamp techniques in ganglion cells It is thought that normal spontaneous release activates AMPA receptors located immediately below the active release zone Fig.
The patch recordings of sEPSCs, under conditions of hyperosmotic Ringer to enhance rates of spontaneous events, reveal large and small as well as fast and slow events Fig. But small amplitude events still are seen Fig.
Further, a maintained inward current is also blocked by both these antagonists, suggesting bipolar-cell ribbon synapses transfer information across a broad temporal spectrum. Vesicular release at the bipolar ribbon synapse occurs in a calcium-dependent manner , though there does not appear to be a selective requirement for calcium, as other divalent ions, such as strontium and barium, can stimulate exocytosis, though to a lesser degree These channels are located on the axon terminal membrane.
Exocytosis occurs in two phases. The depleted pool is restocked with a time constant of about 8s Both the fast and slow phases are calcium-dependent, though they display differential sensitivities to calcium buffers Following neurotransmitter release, the vesicular membrane is recovered rapidly and continuously , The continual cycling of vesicles through the processes of exocytosis and endocytosis, is compatible with tonic release of neurotransmitter This is suspected as bipolar cells generate sustained responses to light, and at least in some cases, transmit sustained signals to postsynaptic neurons 1.
Though neurotransmitter is released following continuous or paired-pulse stimulation of the terminals, release decreases with time , This synaptic depression is believed to be due to depletion of the readily releasable pool and a decrease in exocytosis of this pool The pharmacology and kinetics of the mammalian ribbon synapse between rod bipolar cells and AII amacrine cells has been studied by simultaneous patch recording of presynaptic and postsynaptic cells This glutamatergic synapse uses exclusively AMPA receptors Within the retinal inner plexiform layer there is a transformation from the largely sustained light response of bipolar cells to the largely transient responses of amacrine cells 1.
The mechanism of this transformation is a major topic for retinal neural circuitry. Rod bipolar cells respond to maintained light stimuli with maintained depolarizations , whereas the AII amacrine response to light is a transient depolarization , Singer and Diamond argue that vesicle depletion, at least a higher stimulus levels, is a major contributor to the sustained-transient transformation , The rod-bipolar-to-AII synapse is fast, rising to peak in about 1 ms following depolarization of the rod bipolar.
It is also transient, responding to a depolarizing rectangular voltage step in the presynaptic rod bipolar with a saw-toothed waveform decaying to a lesser steady-state release level within 20 msec. Presynaptic calcium currents that lead to vesicle release are L-type and sustained and do not explain the decay The sustained-to-transient transformation occurs even in the presence of inhibitory synaptic blockers that block reciprocal GABA A feedback.
GABA feedback could be observed as a delayed transient outward current in the rod bipolar recording, but did not measurably alter synaptic release. After the decaying phase of the response completes, a residual train of small synaptic events persists.
The transient waveform slows, but is evident, even at stimulation threshold Decline in the number of available vesicles reduces the number of vesicles released over time, even though for an individual vesicle this probability may remain constant. This is typical of synaptic transmission. One unique feature of this synapse however is synchronous release of vesicle pairs Singer and Diamond estimate the readily releasable pool in the rat rod-bipolar-cell terminal is in net about 70 vesicles, which amounts to about 7 vesicles per ribbon.
The synapse appears able to replace vesicles at about 0. Release is easily depressed in paired pulse experiments and recovers with a time constant only of about 4 s, but sustained exocytosis appears to accelerate vesicle recovery. These properties may confer the ability for synaptically-based neural adaptation ON bipolar cells appear uniquely vulnerable to insult.
The mGluR6 receptor, for example, can be selectively removed i. This can be accomplished through a variety of techniques, such as use of selective pharmacological blocking agents i. Further, naturally occurring mutations and disease processes related to mGluR6 selectively target ON bipolar cells.
Other disease processes also single out ON bipolar cells. Surprisingly humans or animal models with ON-bipolar deficit s perform visual tasks relatively normally. The major problem is loss of nocturnal vision, which appears dependent on the physiological integrity of a single ON bipolar-cell type, the mammalian rod bipolar cell. The electrophysiological consequences of site-directed mutagenisis directed at the ON pathway are seen in figure 4 for mGluR6 deficient mice.
The electroretinographic b-wave component, which arises from the activity of ON bipolar cells, is abolished These authors further demonstrate that light-evoked field potentials from the superior colliculus, which in mouse is the main termination site for ganglion cell axons, lack ON responses, though OFF-type waves appear. In wild type mice, transient collicular waves are seen at both onset and cessation of light stimuli. The altered mGluR6 physiology would seem to imply a behavioral deficit.
Interestingly some tests do suggest deficits in behavior while others do not. In a shuttle box avoidance learning analysis, both mutant and wild type mice performed equally well Since the original site-directed mutant line was created, a forward-genetic mGluR6-mutant line, nob4, has been found Circadian clocks, characterized by wheel running activity in the dark phase, are normal in both mutants. In each mutant light stops this activity ,
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