Yoshimi Kamiyama

Ionic current model of the vertebrate rod photoreceptor.

We describe voltage- and calcium-dependent ionic currents in the photoreceptor inner segments similar to the Hodgkin and Huxley (Journal of Physiology, 117, 500-544, 1952) equations. The model is used to describe both rods and cones by adjusting parameters. To simulate the light response, the inner segment model was connected with the phototransduction model proposed by Torre et al. (Cold Spring Harbor Symposia on Quantitative Biology, 55, 563-573, 1990). The role of individual ionic currents in the inner segment in shaping the light response was analyzed through computer simulations. The results suggest that: (1) the transient hyperpolarization to a bright flash is generated by Ih; (2) the oscillation after prolonged hyperpolarization in rods results from the interaction among Ica, IK(Ca), and ICI(Ca). Since the present model describes the biophysical processes from phototransduction to voltage response, the model can be used for analyzing the light response properties of the photoreceptors quantitatively.

Reconstruction of retinal horizontal cell responses by the ionic current model

An ionic current model of the retinal horizontal cell is constructed. The horizontal cell models are interconnected by gap junctions to form a horizontal cell layer. The light response properties of the L-type horizontal cell are analyzed using this model. We demonstrate the functional role of each ionic current and the role of the feedback loop between cones and horizontal cells. The present study provides insight into the dynamic relationships between characteristics on the cellular level and on the multi-cellular level for producing the light response in horizontal cells.

Ionic current model of bipolar cells in the lower vertebrate retina

We propose an ionic current model of bipolar cells based on the published experimental data. Five types of ionic currents identified in bipolar cell bodies, Ih, IKv, IA, ICa and IK(Ca) were described by a mathematical formulation similar to the Hodgkin and Huxley (Journal of Physiology, 117, 500-544, 1952) equations. The model parameters were estimated from the voltage clamp data. In simulation, we demonstrate that the present model reproduces not only the voltage clamp responses but also the current clamp responses of the bipolar cells. As a result, the model provides a better understanding of the functional role of the ionic currents in bipolar cells in generating the electrical responses.

Physiological engineering model of the outer retina

In the vertebrate retina, the outer plexiform layer which consists of synaptic connections among photoreceptors, horizontal cells and bipolar cells, plays a fundamental role in color- and spatial-information processings. Developing a quantitative model of the outer retina is essential toward better understanding of the outer plexiform layer. Here we propose ionic current models of photoreceptor, horizontal cell and bipolar cells based on the published experimental data. The models provide a better understanding of the functional role of the ionic currents in outer retinal cells in generating the electrical responses. We also discuss how the function of the retinal outer plexiform layer may be studied by constructing a network model from the ionic current based single cell models.

Physiological Engineering Model Of The Retinal Horizontal Cell Layer

Color and spatial opponent signals are essential properties of the visual system. These properties are formulated at a very early stage in the so-called retinal outerplexiform layer. To elucidate the underlying neural mechanisms, we constructed a model of the horizontal cell layer. The model consists of red- and green-sensitive cones, L- and R/G-type horizontal cells. The light induced transmitter release from photoreceptors is mimicked by a third order linear system. The horizontal cell is expressed by Hodgkin-Huxley type equations in terms of relevant ionic currents. To make the horizontal cell layer, each horizontal cell is connected by gap junctional linear conductance. The main input to L- and R/G-type horizontal cells comes from red- and green-sensitive cones, respectively. The L-type horizontal cell has a negative feedback connection to photoreceptors. Computer simulation of a stimulus displacemnet produced dynamic charactersitics very similar to the experimental results in the L-type horizontal cell layer. However, the dynamic response of the R/G-type horizontal cell differed from the experimental data without a negative feedback from R/G-type horizontal cell to green-sensitive cone. This suggests that R/G-type horizontal cell may also have feedback synapse to the green-sensitive cone, although conclusive physiological evidence has not yet been found. We also simulated bipolar cell responses and confirmed that bipolar cells respond to the local contrast change by mediation of the surrounding effect from horizontal cells.

Analysis of light responses of the retinal bipolar cells based on ionic current model

The outer retina which consists of photoreceptor, horizontal cell and bipolar cell is considered as a fundamental neural circuit for spatial and color information processings (Kaneko, 1987). We have developed mathematical models of those cells based on their ionic current mechanisms to analyze the information processings in outer plexiform layer (OPL) of retina (Kamiyama et al., 1996; Usui et al., 1996a, b). In order to further understand information processing in bipolar cells, mathematical models of synaptic connection in OPL have to be constructed. In general, the following sequence of events at the OPL synapse during neurotransmission is involved: 1) At rest in the dark, the synaptic terminal of photoreceptor is depolarized. The depolarization of the terminal activates voltage-gated calcium channels, allowing the entry of calcium ions. 2) The entry of calcium ions into the terminal near the release sites triggers some unknown sequence of events leading to the fusion to the plasma membrane of vesicles containing neurotransmitter glutamates. 3) The glutamates diffuse across the synaptic cleft and make contact with the postsynaptic membrane of bipolar cells. 4) The binding of glutamate to the receptors of the dendrite of bipolar cell causes changes in glutamate induced currents. The release of glutamate is suppressed when photoreceptors are hyperpolarized by light. In the present study, we modeled ionotropic- and metabotropic-type of glutamate induced current of bipolar cell based on available physiological data. We also reconstructed a neural circuit of photoreceptor and bipolar cell by integrating the synaptic models into the model of the bipolar cell body, and analyzed light response properties of a bipolar cell.

Ionic current model for the inner-segment of a retinal photoreceptor

From the morphological point of view, the retinal photoreceptor is composed of the outer segment, the inner segment, and the synapse. Each of these has its own functional role. The outer segment receives light stimulation and changes it into the photosensitive current. The inner segment forms the photoresponse through the interaction between that current change and the various ionic currents existing in the inner segment. The synapse adjusts the release of the information transmission substance according to the photoresponse, and transmits the information to the bipolar cell and the horizontal cell. Although there have been many physiological studies concerning these photoreceptor functions, a model must be constructed and a simulation analysis must be applied to that model in order to clarify such details of the information processing function as the behavior of the various ionic currents of the photoreceptor in the photoresponse, as well as their roles. From such a viewpoint, this paper constructs a model for the ionic currents based on physiological knowledge of the membrane potential-dependent current existing in the inner segment of the photoreceptor. Then, a Ca2+-dependent current is considered and the behavior of the ionic current corresponding to the change of Ca2+ density in the cell is modeled, considering the intracell mechanism for Ca2+. It is verified that the model exhibits the same behavior in terms of the membrane potential and the membrane current response of the inner segment of the photoreceptor. The time-course of each ionic current in the Ca2+ spike period is determined by simulation, which has been difficult to measure by physiological experiments. As a result, the modification effect of each ionic current on the Ca2+ spike is indicated. The difference of the spike waveform between the membrane potential-dependent K+-current blocking period and the control state is also accounted for, based on the dynamic behavior of the ionic currents. The effect of the intracellular Ca2+ density change on the membrane potential response is analyzed, and it is shown that the termination of the Ca2+ spike is greatly affected by the activation of the Ca2+ dependent Cl− current accompanying the intracellular Ca2+ density increase. The authors believe that the model for the inner segment of the photoreceptor presented in this paper will contribute greatly to future studies of the retinal function through analysis from a physiological engineering point of view.

A method for estimating gap junctional conductance between the retinal horizontal cells

Gap junction between retinal horizontal cells plays an important role in generating the center-surround antagonistic receptive field. However, there are technical difficulties involved in measurement of the gap junctional conductance from membrane potential of horizontal cells using the ionic current model. To evaluate the proposed method, the gap junctional conductance was estimated from test data generated by the horizontal cell layer model. Conductance can be estimated with high accuracy. This method is also applied to experimental data recorded from the L-type cell of carp retina.

Ionic current model of the retinal photoreceptor and simulation analysis of the photoresponses

The fact that the reception of optical information by the retinal photoreceptor and the process of its transformation to the membrane voltage response are due to an interaction between the photocurrent from the outer segment and each ionic current in the inner segment has been confirmed by many physiological experiments. However, the properties of each ionic current in the photoreceptor have not been clear since no physiologically reliable model of the retinal photoreceptor has been constructed. n n n nThis paper proposes a model of a retinal photoreceptor, which is a combination of the outer segment model (devised by Torre et al.) and the inner segment model (devised by the present authors). It has been confirmed that this model can accurately represent the electron physiological properties of a retinal photoreceptor. Using this model simulation, the relationship between the photocurrent and the photoresponse dynamics, and an oscillatory phenomena caused by a strong light flash have been analyzed. The results show that the dynamic and nonlinear response characteristics of a retinal photoreceptor are due to the interactions between the nonlinear ionic current in the inner segment and the mechanism of the intracellular calcium.

A Method for Estimating the Neural Input to a Neuron using the Ionic Current Model

The ionic current properties of a neuron play a fundamental role for generating the voltage responses such as post synaptic potential and action potential. The voltage- and time-dependent characteristics of each ionic current can be measured by applying voltage clamp techniques which lead to the precise measurement of the membrane ionic currents underlying the voltage response. From these measurements it is possible to obtain the exact mathematical descriptions of the ionic current in response to electrical and chemical stimuli similar to Hodgkin-Huxley equations[1]. The ionic current model provides a basis for understanding how the individual ionic current flows during the response and/or predicts the blocking effect of a particular ionic channel.