Interstitial cells of Cajal in the striated musculature of the mouse esophagus

A key feature of signal processing in the mammalian retina is parallel processing, where the segregation of visual information, e.g., brightness, darkness, and color, starts at the first synapse in the retina, the photoreceptor synapse. These various aspects are transmitted in parallel from the input neurons of the retina, the photoreceptor cells, through the interconnecting bipolar cells, to the output neurons, the ganglion cells. The photoreceptors and bipolar cells release a single excitatory neurotransmitter, glutamate, at their synapses. This parsimony is contrasted by the expression of a plethora of glutamate receptors, receptor subunits, and isoforms. The detailed knowledge of the synaptic distribution of glutamate receptors thus is of major importance in understanding the mechanisms of retinal signal processing. This review intends to highlight recent studies on the distribution of glutamate receptors at the photoreceptor synapses of the mammalian retina.     

Network Adaptation Improves Temporal Representation of Naturalistic Stimuli in Drosophila Eye: II Mechanisms

Retinal networks must adapt constantly to best present the ever changing visual world to the brain. Here we test the hypothesis that adaptation is a result of different mechanisms at several synaptic connections within the network. In a companion paper (Part I), we showed that adaptation in the photoreceptors (R1–R6) and large monopolar cells (LMC) of the Drosophila eye improves sensitivity to under-represented signals in seconds by enhancing both the amplitude and frequency distribution of LMCs'' voltage responses to repeated naturalistic contrast series. In this paper, we show that such adaptation needs both the light-mediated conductance and feedback-mediated synaptic conductance. A faulty feedforward pathway in histamine receptor mutant flies speeds up the LMC output, mimicking extreme light adaptation. A faulty feedback pathway from L2 LMCs to photoreceptors slows down the LMC output, mimicking dark adaptation. These results underline the importance of network adaptation for efficient coding, and as a mechanism for selectively regulating the size and speed of signals in neurons. We suggest that concert action of many different mechanisms and neural connections are responsible for adaptation to visual stimuli. Further, our results demonstrate the need for detailed circuit reconstructions like that of the Drosophila lamina, to understand how networks process information.     

Photoreceptor processing speed and input resistance changes during light adaptation correlate with spectral class in the bumblebee, Bombus impatiens

Colour vision depends on comparison of signals from photoreceptors with different spectral sensitivities. However, response properties of photoreceptor cells may differ in ways other than spectral tuning. In insects, for example, broadband photoreceptors, with a major sensitivity peak in the green region of the spectrum (>500 nm), drive fast visual processes, which are largely blind to chromatic signals from more narrowly-tuned photoreceptors with peak sensitivities in the blue and UV regions of the spectrum. In addition, electrophysiological properties of the photoreceptor membrane may result in differences in response dynamics of photoreceptors of similar spectral class between species, and different spectral classes within a species. We used intracellular electrophysiological techniques to investigate response dynamics of the three spectral classes of photoreceptor underlying trichromatic colour vision in the bumblebee, Bombus impatiens, and we compare these with previously published data from a related species, Bombus terrestris. In both species, we found significantly faster responses in green, compared with blue- or UV-sensitive photoreceptors, although all 3 photoreceptor types are slower in B. impatiens than in B. terrestris. Integration times for light-adapted B. impatiens photoreceptors (estimated from impulse response half-width) were 11.3 ± 1.6 ms for green photoreceptors compared with 18.6 ± 4.4 ms and 15.6 ± 4.4 for blue and UV, respectively. We also measured photoreceptor input resistance in dark- and light-adapted conditions. All photoreceptors showed a decrease in input resistance during light adaptation, but this decrease was considerably larger (declining to about 22% of the dark value) in green photoreceptors, compared to blue and UV (41% and 49%, respectively). Our results suggest that the conductances associated with light adaptation are largest in green photoreceptors, contributing to their greater temporal processing speed. We suggest that the faster temporal processing of green photoreceptors is related to their role in driving fast achromatic visual processes.     

An elementary information processing component in the circuitry of the retina generating the on-responses

A pattern of neural connections that is a compulsory feature of photoreceptor terminals and is referred to as the synaptic ribbon complex was analyzed, and by combination of the structural information and information gained by intracellular recordings from photoreceptors, horizontal cells, and bipolar cells, it is possible to explain how the hyperpolarizing effect of light stimulating the photoreceptors is changed to a depolarization of depolarizing bipolar cells. The sign reversal is accomplished by the hyperpolarizing action of the horizontal cells on the photoreceptors, which blocks the transmission between the photoreceptors and the bipolar cells. This blocking action is controlled by the photoreceptor and it functions like a gate that is opened only when the photoreceptor is stimulated by light. The synaptic ribbon complex offers an example of an elementary information processing component with three input channels to the bipolar cells with each channel contributing a different piece of information and with the processing occurring presynaptically. Additional processing of information occurs within the dendritic tree through interactions of the responses of the individual dendritic endings to different types of input. This interaction can involve partial blocking of the conduction within the dendritic tree, making the interaction considerably more complex than simple summation. The responses recorded intracellularly from neurons reveal only the end result of the processing of information at the level of that neuron.     

Light adaptation in Drosophila photoreceptors: II. Rising temperature increases the bandwidth of reliable signaling

It is known that an increase in both the mean light intensity and temperature can speed up photoreceptor signals, but it is not known whether a simultaneous increase of these physical factors enhances information capacity or leads to coding errors. We studied the voltage responses of light-adapted Drosophila photoreceptors in vivo from 15 to 30 degrees C, and found that an increase in temperature accelerated both the phototransduction cascade and photoreceptor membrane dynamics, broadening the bandwidth of reliable signaling with an effective Q(10) for information capacity of 6.5. The increased fidelity and reliability of the voltage responses was a result of four factors: (1) an increased rate of elementary response, i.e., quantum bump production; (2) a temperature-dependent acceleration of the early phototransduction reactions causing a quicker and narrower dispersion of bump latencies; (3) a relatively temperature-insensitive light-adapted bump waveform; and (4) a decrease in the time constant of the light-adapted photoreceptor membrane, whose filtering matched the dynamic properties of the phototransduction noise. Because faster neural processing allows faster behavioral responses, this improved performance of Drosophila photoreceptors suggests that a suitably high body temperature offers significant advantages in visual performance.     

Neurotransmitters alter the numbers of synapses and organelles in photoreceptor terminals in the lamina of the housefly, Musca domestica

Various organelles in the lamina terminals of housefly photoreceptors exhibit daily rhythms having a circadian basis. These include changes in the numbers of photoreceptor tetrad and L2 feedback synapses, and longitudinal movements of screening pigment. Circadian information has previously been suggested to spread from the clock to the lamina via widefield cells expressing either 5-hydroxytryptamine or pigment-dispersing hormone-like immunoreactivity. We examined the action of these neuromodulators, and other candidate neurotransmitters, 4 h after injecting either the transmitter or a control into the medulla. We counted electron microscope profiles of organelles that normally exhibit circadian changes, and two types of invagination into photoreceptor terminals, capitate projections and inter-receptor invaginations. No single substance mediated the changes observed. Injected pigment-dispersing hormone peptide decreased the number of pigment granules, implicating this peptide in screening pigment migration, but produced no changes in synapse-related organelles. α-Aminobutyric acid exclusively decreased the number of L2 feedback synapses. Responses to other transmitters were specific, and often large, but generally not statistically significant. Histamine, for example, may decrease the number of tetrads, possibly by direct autoregulation. The results suggest that there is likely to be more than one effector in the circadian pathways to the lamina. Accepted: 11 August 1998     

Ribbon synapses of the retina

Vision is a highly complex task that involves several steps of parallel information processing in various areas of the central nervous system. Complex processing of visual signals occurs as early as at the retina, the first stage in the visual system. Various aspects of visual information are transmitted in parallel from the photoreceptors (the input neurons of the retina) through their interconnecting bipolar cells to the ganglion cells (the output neurons). Photoreceptors and bipolar cells transfer information via the release of the neurotransmitter glutamate at a specialized synapse, the ribbon synapse. Although known from early days of electron microscopy, the precise functioning of ribbon synapses has yet to be explained. In this review, we highlight recent advances towards understanding the molecular composition and function of this enigmatic synapse.This study was supported by a grant from the Deutsche Forschungsgemeinschaft (BR 1643/4-1) to J.H.B.     

Light adaptation in Drosophila photoreceptors: I. Response dynamics and signaling efficiency at 25 degrees C

Besides the physical limits imposed on photon absorption, the coprocessing of visual information by the phototransduction cascade and photoreceptor membrane determines the fidelity of photoreceptor signaling. We investigated the response dynamics and signaling efficiency of Drosophila photoreceptors to natural-like fluctuating light contrast stimulation and intracellular current injection when the cells were adapted over a 4-log unit light intensity range at 25 degrees C. This dual stimulation allowed us to characterize how an increase in the mean light intensity causes the phototransduction cascade and photoreceptor membrane to produce larger, faster and increasingly accurate voltage responses to a given contrast. Using signal and noise analysis, this appears to be associated with an increased summation of smaller and faster elementary responses (i.e., bumps), whose latency distribution stays relatively unchanged at different mean light intensity levels. As the phototransduction cascade increases, the size and speed of the signals (light current) at higher adapting backgrounds and, in conjunction with the photoreceptor membrane, reduces the light-induced voltage noise, and the photoreceptor signal-to-noise ratio improves and extends to a higher bandwidth. Because the voltage responses to light contrasts are much slower than those evoked by current injection, the photoreceptor membrane does not limit the speed of the phototransduction cascade, but it does filter the associated high frequency noise. The photoreceptor information capacity increases with light adaptation and starts to saturate at approximately 200 bits/s as the speed of the chemical reactions inside a fixed number of transduction units, possibly microvilli, is approaching its maximum.     

Glycine input induces the synaptic facilitation in salamander rod photoreceptors

Glycinergic synapses in photoreceptors are made by centrifugal feedback neurons in the network, but the function of the synapses is largely unknown. Here we report that glycinergic input enhances photoreceptor synapses in amphibian retinas. Using specific antibodies against a glycine transporter (GlyT2) and glycine receptor β subunit, we identified the morphology of glycinergic input in photoreceptor terminals. Electrophysiological recordings indicated that 10 μM glycine depolarized rods and activated voltage-gated Ca²⁺ channels in the neurons. The effects facilitated glutamate vesicle release in photoreceptors, meanwhile increased the spontaneous excitatory postsynaptic currents in Off-bipolar cells. Endogenous glycine feedback also enhanced glutamate transmission in photoreceptors. Additionally, inhibition of a Cl⁻ uptake transporter NKCC1 with bumetanid effectively eliminated glycine-evoked a weak depolarization in rods, suggesting that NKCC1 maintains a high Cl⁻ level in rods, which causes to depolarize in responding to glycine input. This study reveals a new function of glycine in retinal synaptic transmission.     

Membrane filtering properties of the bumblebee (Bombus terrestris) photoreceptors across three spectral classes

Filtering properties of the membrane form an integral part of the mechanisms producing the light-induced electrical signal in insect photoreceptors. Insect photoreceptors vary in response speed between different species, but recently it has also been shown that different spectral photoreceptor classes within a species possess diverse response characteristics. However, it has not been quantified what roles phototransduction and membrane properties play in such diversity. Here, we use electrophysiological methods in combination with system analysis to study whether the membrane properties could create the variation of the response speed found in the bumblebee (Bombus terrestris) photoreceptors. We recorded intracellular responses from each photoreceptor class to white noise-modulated current stimuli and defined their input resistance and linear filtering properties. We found that green sensitive cells exhibit smaller input resistance and membrane impedance than other cell classes. Since green sensitive cells are the fastest photoreceptor class in the bumblebee retina, our results suggest that the membrane filtering properties are correlated with the speed of light responses across the spectral classes. In general, our results provide a compelling example of filtering at the sensory cell level where the biophysical properties of the membrane are matched to the performance requirements set by visual ecology.     

A positive feedback synapse from retinal horizontal cells to cone photoreceptors

Cone photoreceptors and horizontal cells (HCs) have a reciprocal synapse that underlies lateral inhibition and establishes the antagonistic center-surround organization of the visual system. Cones transmit to HCs through an excitatory synapse and HCs feed back to cones through an inhibitory synapse. Here we report that HCs also transmit to cone terminals a positive feedback signal that elevates intracellular Ca(2+) and accelerates neurotransmitter release. Positive and negative feedback are both initiated by AMPA receptors on HCs, but positive feedback appears to be mediated by a change in HC Ca(2+), whereas negative feedback is mediated by a change in HC membrane potential. Local uncaging of AMPA receptor agonists suggests that positive feedback is spatially constrained to active HC-cone synapses, whereas the negative feedback signal spreads through HCs to affect release from surrounding cones. By locally offsetting the effects of negative feedback, positive feedback may amplify photoreceptor synaptic release without sacrificing HC-mediated contrast enhancement.     

Activity-independent prespecification of synaptic partners in the visual map of Drosophila

Specifying synaptic partners and regulating synaptic numbers are at least partly activity-dependent processes during visual map formation in all systems investigated to date . In Drosophila, six photoreceptors that view the same point in visual space have to be sorted into synaptic modules called cartridges in order to form a visuotopically correct map . Synapse numbers per photoreceptor terminal and cartridge are both precisely regulated . However, it is unknown whether an activity-dependent mechanism or a genetically encoded developmental program regulates synapse numbers. We performed a large-scale quantitative ultrastructural analysis of photoreceptor synapses in mutants affecting the generation of electrical potentials (norpA, trp;trpl), neurotransmitter release (hdc, syt), vesicle endocytosis (synj), the trafficking of specific guidance molecules during photoreceptor targeting (sec15), a specific guidance receptor required for visual map formation (Dlar), and 57 other novel synaptic mutants affecting 43 genes. Remarkably, in all these mutants, individual photoreceptors form the correct number of synapses per presynaptic terminal independently of cartridge composition. Hence, our data show that each photoreceptor forms a precise and constant number of afferent synapses independently of neuronal activity and partner accuracy. Our data suggest cell-autonomous control of synapse numbers as part of a developmental program of activity-independent steps that lead to a "hard-wired" visual map in the fly brain.     

Membrane parameters,signal transmission,and the design of a graded potential neuron

1. The large monopolar cells (LMCs) of the fly, Calliphora vicina, visual system transmit graded potentials over distances of up to 1.0 mm. An electrical model was constructed to investigate the design principles relating their membrane parameters to signal transmission and filtering. 2. Using existing anatomical measurements, a cable model (van Hateren 1986) was fitted to the measured intracellular responses of the cells to injected current. The LMC has three functional components: a distal synaptic zone of low impedance, an axon with high specific membrane resistance (greater than 50.10(5) M omega.micron 2), and a high impedance proximal terminal. These components interact to transmit information efficiently. The low input impedance synaptic zone charges and discharges the axon rapidly, ensuring a good frequency response. The high resistance axon conducts signals with little decrement. The model shows that graded potential transmission in LMCs selectively filters synaptic noise and predicts the changes in response waveform that occur during transmission. 3. The parameters of the model were adjusted to determine the relative costs and benefits of alternative cable designs. The design used in LMCs is the most expensive and the most effective. It requires the largest currents to generate responses but transmits signals with least decrement. Parallel neurons in the fly visual system have fewer input synapses and this could low-pass filter their graded response.     

Direct innervation of GnRH neurons by encephalic photoreceptors in birds

In nonmammalian vertebrates, photic cues that regulate the timing of seasonal reproductive cyclicity are detected by nonretinal, nonpineal deep brain photoreceptors. It has long been assumed that the underlying mechanism involves the transmission of photic information from the photoreceptor to a circadian system, and thence to the reproductive axis. An alternative hypothesis is that there is direct communication between the brain photoreceptor and the reproductive axis. In the present study, light and confocal microscopy reveal that gonadotropin releasing hormone (GnRH) neurons and processes are scattered among photoreceptor cells (identified by their opsin-immunoreactivity) in the lateral septum (SL). In the median eminence (ME), opsin and GnRH immunoreactive fibers overlap extensively. Single and double label ultrastructural immunocytochemistry indicate that in the SL and preoptic area (POA), opsin positive terminals form axo-dendritic synapses onto GnRH dendrites. In the ME, opsin and GnRH terminals lie adjacent to each other, make contact with tanycytes, or terminate on the hypophyseal portal capillaries. These results reveal thatbrain photoreceptors communicate directly with GnRH-neurons; this represents a means by which photoperiodic information reaches the reproductive axis.     

Adaptations for vision in dim light: impulse responses and bumps in nocturnal spider photoreceptor cells (<Emphasis Type="Italic">Cupiennius</Emphasis><Emphasis Type="Italic">salei</Emphasis> Keys)

The photoreceptor cells of the nocturnal spider Cupiennius salei were investigated by intracellular electrophysiology. (1) The responses of photoreceptor cells of posterior median (PM) and anterior median (AM) eyes to short (2 ms) light pulses showed long integration times in the dark-adapted and shorter integration times in the light-adapted state. (2) At very low light intensities, the photoreceptors responded to single photons with discrete potentials, called bumps, of high amplitude (2–20 mV). When measured in profoundly dark-adapted photoreceptor cells of the PM eyes these bumps showed an integration time of 128 ± 35 ms (n = 7) whereas in dark-adapted photoreceptor cells of AM eyes the integration time was 84 ± 13 ms (n = 8), indicating that the AM eyes are intrinsically faster than the PM eyes. (3) Long integration times, which improve visual reliability in dim light, and large responses to single photons in the dark-adapted state, contribute to a high visual sensitivity in Cupiennius at night. This conclusion is underlined by a calculation of sensitivity that accounts for both anatomical and physiological characteristics of the eye.     

Electrical responses of <Emphasis Type="Italic">Lymnaea stagnalis</Emphasis> to light stimulation: Effect of divalent cations

The effects of Ca²⁺, Mg²⁺ and Mn²⁺ on light-evoked electrical responses, ERG and action potentials of optic nerve fibers, were studied in an isolated eye of Lymnaea stagnalis. Signals of both types persisted with minor changes when Mg²⁺ concentration in the bath solution was increased up to 15 mM. This finding suggests that action potentials of photoreceptor cells are transmitted via their axons directly to central ganglia without a relay in chemical synapses on interneurons. At the same time, the changed spiking pattern may indicate chemical interactions between photoreceptors cells themselves. In the presence of 4 mM EDTA or 10 mM Mn²⁺, both ERG waves and spiking activity were considerably depressed, probably, as a result of impaired phototransduction in photoreceptor cells.     

Maximizing contrast resolution in the outer retina of mammals

The outer retina removes the first-order correlation, the background light level, and thus more efficiently transmits contrast. This removal is accomplished by negative feedback from horizontal cell to photoreceptors. However, the optimal feedback gain to maximize the contrast sensitivity and spatial resolution is not known. The objective of this study was to determine, from the known structure of the outer retina, the synaptic gains that optimize the response to spatial and temporal contrast within natural images. We modeled the outer retina as a continuous 2D extension of the discrete 1D model of Yagi et al. (Proc Int Joint Conf Neural Netw 1: 787–789, 1989). We determined the spatio-temporal impulse response of the model using small-signal analysis, assuming that the stimulus did not perturb the resting state of the feedback system. In order to maximize the efficiency of the feedback system, we derived the relationships between time constants, space constants, and synaptic gains that give the fastest temporal adaptation and the highest spatial resolution of the photoreceptor input to bipolar cells. We found that feedback which directly modulated photoreceptor calcium channel activation, as opposed to changing photoreceptor voltage, provides faster adaptation to light onset and higher spatial resolution. The optimal solution suggests that the feedback gain from horizontal cells to photoreceptors should be ∼0.5. The model can be extended to retinas that have two or more horizontal cell networks with different space constants. The theoretical predictions closely match experimental observations of outer retinal function.     

Synaptic activity of frog retinal photoreceptors. A peroxidase uptake study

The uptake of horseradish peroxidase (HRP) into membranous structures, detectable by light and electron microscopy, is used here to monitor the synaptic activity of photoreceptors of isolated frog retinas maintained in the dark or under various illumination conditions. The major findings are: (a) Neurotransmission from photoreceptor terminals seems to involve the same types of endocytic membrane-retrieval processes that occur at other nerve terminals. Presumably, the endocytic processes compensate for exocytic events associated with neurotransmission. The retrieved membrane is "recycled" to form vesicles. Some of these accumulate near the synaptic ribbons, perhaps indicating reutilization for exocytosis. On the other hand, some retrieved membrane evidently is degraded via multivesicular bodies that appear to undergo "retrograde" transport from the receptor synapses to the myoid regions. (b) Photoreceptor terminals take up much HRP in the dark. Steady illumination markedly decreases uptake by rods. Uptake by cones is notably reduced only at illumination intensities higher than those that have maximal effects on rods. (c) The decrease in rod HRP uptake with light is reversible when retinas are allowed to adapt to the dark, if the light exposures used were at intensities that bleach very little visual pigment. Such "recovery" is not observed after light exposures that bleach a considerable amount of visual pigment. The cones recover their dark levels of HRP uptake even after light exposures that bleach considerable amounts of visual pigment. The changes in HRP uptake that we observe parallel expectations for photoreceptor synaptic neurotransmission derived from indirect physiological evidence.     

Synaptic plasticity and functionality at the cone terminal of the developing zebrafish retina

Previous studies have analyzed photoreceptor development, some inner retina cell types, and specific neurotransmitters in the zebrafish retina. However, only minor attention has been paid to the morphology of the synaptic connection between photoreceptors and second order neurons even though it represents the transition from the light sensitive receptor to the neuronal network of the visual system. Here, we describe the appearance and differentiation of pre- and postsynaptic elements at cone synapses in the developing zebrafish retina together with the maturation of the directly connecting second order neurons and a dopaminergic third order feedback-neuron from the inner retina. Zebrafish larvae were examined at developmental stages from 2 to 7dpf (days postfertilization) and in the adult. Synaptic maturation at the photoreceptor terminals was examined with antibodies against synapse associated proteins. The appearance of synaptic plasticity at the so-called spinule-type synapses between cones and horizontal cells was assessed by electron microscopy, and the maturation of photoreceptor downstream connection was identified by immunocytochemistry for GluR4 (AMPA-type glutamate receptor subunit), protein kinase beta(1) (mixed rod-cone bipolar cells), and tyrosine hydroxylase (dopaminergic interplexiform cells). We found that developing zebrafish retinas possess first synaptic structures at the cone terminal as early as 3.5dpf. Morphological maturation of these synapses at 3.5-4dpf, together with the presence of synapse associated proteins at 2.5dpf and the maturation of second order neurons by 5dpf, indicate functional synaptic connectivity and plasticity between the cones and their second order neurons already at 5dpf. However, the mere number of spinules and ribbons at 7dpf still remains below the adult values, indicating that synaptic functionality of the zebrafish retina is not entirely completed at this stage of development.     

Histamine metabolism in the visual system of the horseshoe crab Limulus polyphemus

There is now strong evidence that arthropod photoreceptors use histamine as a neurotransmitter. The synthesis, storage and release of histamine from arthropod photoreceptors have been demonstrated, and the postsynaptic effects of histamine and the endogenous neurotransmitter are similar. However, a full understanding of these photoreceptor synapses also requires knowledge of histamine inactivation and metabolism. Relatively little is known about histamine metabolism in the nervous system of arthropods, and mechanisms appear to differ with the species. This study focuses on histamine metabolism in visual tissues of the horseshoe crab Limulus polyphemus, a chelicerate. We present two major findings: (1) histamine is metabolized to imidazole acetic acid and to gamma-glutamyl histamine. (2) relatively low levels of histamine metabolites accumulate in Limulus visual tissues.