Metabotropic glutamate receptor-mediated hetero-synaptic interaction of red- and green-cone inputs to LHC of carp retina

doi:10.1016/S0361-9230(03)00015-7

Brain Research Bulletin

Volume 60, Issues 1–2, 15 April 2003, Pages 67-71

https://doi.org/10.1016/S0361-9230(03)00015-7 Get rights and content

Abstract

The role of presynaptic metabotropic glutamate receptor (mGluR) on the interaction of red- and green-cone signals was investigated in luminosity-type horizontal cell (LHC) of isolated carp retina. It was found that a dim red background could enhance LHC’s light response to green stimulus, and a dim green background was also able to increase the cell’s response to red flash. Such mutual color enhancement was eliminated by application of groups II and III mGluR antagonist (S)-methyl-4-carboxyphenyl-glycine (MCPG). Furthermore, inhibition of glutamate uptake by using d-aspartate (d-Asp) or dl-threo-β-hydroxy-aspartic acid (THA) completely blocked the mutual enhancement of color signals in LHC. However, the GABAergic feedback pathway in the outer retina was unnecessarily involved.

Introduction

In teleost fish retinas, luminosity-type horizontal cell receives excitatory glutamatergic synaptic inputs from both red- and green-sensitive cone photoreceptors while provides negative feedback on various cone photoreceptors 11., 22.. In the dark, photoreceptors continuously release glutamate, which depolarizes luminosity-type horizontal cell (LHC). Light hyperpolarizes the photoreceptors and reduces their glutamate release, which results in a hyperpolarizing response in LHC [5]. Additionally, it has been shown that glutamate transporter at cone photoreceptors is voltage dependent and robust enough to modulate the concentration of glutamate in the synaptic cleft and thus plays a significant role in adjusting the dynamics of LHC’s light response [7].

It has been reported that there existed interaction of red- and green-cone signals in LHC [16], which was described as an increase of LHC’s light response to green flash in the presence of a dim red background light, and vice versa. Kamermans et al. [11] suggested that symmetric sign-inverted feedback synapses from LHC to both red- and green-cone photoreceptors could mediate such mutual color enhancement. On the other hand, the engagement of an asymmetric negative feedback from LHC to green cone photoreceptors alone was proposed, based on the finding that only a brief leading green flash could enhance LHC’s responsiveness to the successive red flash but not vice versa [22]. However, none of the hypothetical models were experimentally examined. Furthermore, Umino et al. [19] reported that the response enhancement was not affected by application of GABA. Nevertheless, the exact physiological mechanisms underlying this process still remain elusive.

A large number of evidence supported that metabotropic glutamate receptors (mGluRs) found at the presynaptic terminals are important in fine tuning of the synaptic transmission [1]. Activation of mGluRs as an autoreceptor may depress neurotransmitter release from the presynaptic neuron, and this inhibitory action would modulate the synaptic output to the postsynaptic neuron [2]. In addition, glutamate may diffuse or spillover from the synaptic cleft and activate the presynaptic mGluRs at the adjacent synapse, which would mediate the crosstalk of neighboring synapses, for example the hetero-synaptic depression observed in cerebellum [15]. The inhibition may be facilitated by glutamate transporter blockers or abolished by mGluR antagonists [18]. Recently, several lines of evidence demonstrated the existence of mGluRs at the terminals of photoreceptors in the vertebrate retina, which was suggested to provide a negative feedback mechanism for regulating glutamate release from photoreceptors 9., 12..

In the present study, we initially confirmed that a dim red background light greatly enhanced the response amplitude of LHC to green test flash, and vice versa. We then found that such mutual color enhancement was related to the activation of mGluRs located at the presynaptic terminals of cone photoreceptors. Blockade of glutamate transporter completely eliminated the mutual enhancement of color signals in LHC, as expected. However, the GABAergic feedback pathway in the outer retina seemed unnecessary.

Section snippets

Materials and methods

Experiments were performed on adult carp (Carassius auratus, body length 15–20 cm) retinas following the procedure similar to the previous report [10]. All procedures strictly conformed to the humane treatment and use of animals as prescribed by the Association for Research in Vision and Ophthalmology. Briefly, the fish was raised in aerated aquarium on a natural light/dark cycle. After 15–25 min of dark adaptation, the fish was decapitated to minimize the animal’s pain and discomfort and eyes

Results

LHC of fish retina receives excitatory synaptic inputs from both red- and green-sensitive cones, which interact nonlinearly 11., 16.. As shown in Fig. 1A, the amplitude of LHC’s response to a moderate green test flash (518 nm, log I=−2.03) was 9.2 mV in the dark. In the presence of a dim red background light (701 nm, log I=−2.23), the cell’s membrane potential was hyperpolarized by 5.2 mV, and its response to the same green stimulus was conspicuously increased to 14.5 mV. The relative response

Discussion

The neural interactions of various photoreceptor inputs fed forward onto horizontal cells (HCs) have been investigated over the years, and various hypothetical models have been proposed to pry the underlying mechanism 11., 22..

In this study we found that the red background light greatly enhanced LHC green response and vice versa, which was consistent with the previous reports of mutual color enhancement [16]. But potentiation or repression of GABAergic activity exerted little effect on the

Acknowledgements

This research was supported by grants from the State Key Basic Research and Development Plan (No. G1999054000) and the National Foundation of Natural Science of China (No. 30170263).

References (23)

R. Anwyl
Metabotropic glutamate receptors: electrophysiological properties and role in plasticity
Brain Res. Rev.
(1999)
A.J. Cochilla et al.
Metabotropic glutamate receptor-mediated control of neurotransmitter release
Neuron
(1998)
H. Hirasawa et al.
Blocking AMPA receptor desensitization prolongs spontaneous EPSC decay times and depolarizes H1 horizontal cells in carp retinal slices
Neurosci. Res.
(2001)
J.F. Hu et al.
Stimulus pattern related plasticity of synapses between cones and horizontal cells in carp retina
Brain Res.
(2000)
M.Y. Min et al.
Activation of AMPA, kainate, and metabotropic receptors at hippocampal mossy fiber synapses: role of glutamate diffusion
Neuron
(1998)
M. Sarantis et al.
The spatial relationship between Muller cell processes and the photoreceptor output synapse
Brain Res.
(1992)
C.A.V. Vandenbranden et al.
Clearance of neurotransmitter from the cone synaptic cleft in goldfish retina
Vision Res.
(1996)
X.L. Yang et al.
Convergence of signals from red-sensitive and green-sensitive cones onto L-type external horizontal cells of the goldfish retina
Vision Res.
(1983)
G.B. Awatramani et al.
Intensity-dependent, rapid activation of presynaptic metabotropic glutamate receptors at a central synapse
J. Neurosci.
(2001)
T.J. Bushell et al.
Pharmacological antagonism of the actions of group II and III mGluR agonists in the lateral perforant path of rat hippocampal slices
Br. J. Pharmacol.
(1996)

D.R. Copenhagen et al.

Release of endogenous excitatory amino acids from turtle photoreceptors

Nature

(1989)

Cited by (6)

Group II metabotropic glutamate receptor agonist promotes retinal ganglion cell survival by reducing neuronal excitotoxicity in a rat chronic ocular hypertension model
2020, Neuropharmacology
Citation Excerpt :
mGluR II is widely distributed in the retina (Cai and Pourcho, 1999; Hartveit et al., 1995). Under physiological conditions, mGluR II has the potential to influence directional selectivity of rabbit RGCs by inhibiting release of acetylcholine from starburst amacrine cells; it also has the potential to modulate the mutual enhancement of color signals in carp Luminosity-type horizontal cells (Luo and Liang, 2003; Jensen, 2006). These studies suggest that mGluR II may play an important role in the processing of visual information.
Glaucoma, the second leading cause of irreversible blindness worldwide, is characterized by the selective death of retinal ganglion cells (RGCs). The group II metabotropic glutamate receptor (mGluR II) activation has been linked to RGC survival, however, the mechanism by which it promotes neuronal survival remains poorly defined. In the present work, we show that extracellular application of LY341495, an mGluR II antagonist could increase the RGC firing frequency, suggesting that activation of mGluR II by endogenously released glutamate could modulate RGC excitability. LY354740, an mGluR II agonist, significantly decreased RGC excitability and the reduced presynaptic excitatory inputs and post-synaptic Ca2+-permeable currents mediated the LY354740-induced effects. By using a well-characterized in vivo male Sprague-Dawley rat glaucoma model, we further demonstrate that in the early stage of experimental glaucoma, the expression of mGluR II dimer-formed protein was significantly reduced, and pre-activation of mGluR II by intravitreal injection of LY354740 before establishment of the glaucoma model could effectively reduce excitatory inputs, thereby reversing hyperexcitability induced by elevated intraocular pressure. Furthermore, LY354740 could increase the expression level of brain-derived neurotrophic factor in the glaucomatous retinas, further protecting RGCs. Our study indicates that the abnormal expression of mGluR II may accelerate RGC apoptosis in glaucoma, and demonstrates that mGluR II agonist LY354740 can be used as a novel method to counter RGC apoptosis in glaucoma.
Retinal ischemia: Mechanisms of damage and potential therapeutic strategies
2004, Progress in Retinal and Eye Research
Retinal ischemia is a common cause of visual impairment and blindness. At the cellular level, ischemic retinal injury consists of a self-reinforcing destructive cascade involving neuronal depolarisation, calcium influx and oxidative stress initiated by energy failure and increased glutamatergic stimulation. There is a cell-specific sensitivity to ischemic injury which may reflect variability in the balance of excitatory and inhibitory neurotransmitter receptors on a given cell. A number of animal models and analytical techniques have been used to study retinal ischemia, and an increasing number of treatments have been shown to interrupt the “ischemic cascade” and attenuate the detrimental effects of retinal ischemia.
Thus far, however, success in the laboratory has not been translated to the clinic. Difficulties with the route of administration, dosage, and adverse effects may render certain experimental treatments clinically unusable. Furthermore, neuroprotection-based treatment strategies for stroke have so far been disappointing. However, compared to the brain, the retina exhibits a remarkable natural resistance to ischemic injury, which may reflect its peculiar metabolism and unique environment. Given the increasing understanding of the events involved in ischemic neuronal injury it is hoped that clinically effective treatments for retinal ischemia will soon be available.
A presynaptic group III mGluR recruits Gβγ/SNARE interactions to inhibit synaptic transmission by cone photoreceptors in the vertebrate retina
2017, Journal of Neuroscience
Localization of metabotropic glutamate receptors in the outer plexiform layer of the goldfish retina
2007, Cell and Tissue Research
Modeling the pre- and post-synaptic components involved in the synaptic modification between cones and horizontal cells in carp retina
2007, Biological Cybernetics
Effect of membrane nonlinearity on retinal LHC's light response
2003, Proceedings of 2003 International Conference on Neural Networks and Signal Processing, ICNNSP'03

View full text

Metabotropic glutamate receptor-mediated hetero-synaptic interaction of red- and green-cone inputs to LHC of carp retina

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Acknowledgements

Brain Res. Rev.

Neuron

Neurosci. Res.

Brain Res.

Neuron

Brain Res.

Vision Res.

Vision Res.

Intensity-dependent, rapid activation of presynaptic metabotropic glutamate receptors at a central synapse

J. Neurosci.

Pharmacological antagonism of the actions of group II and III mGluR agonists in the lateral perforant path of rat hippocampal slices

Br. J. Pharmacol.

Release of endogenous excitatory amino acids from turtle photoreceptors

Nature