Light-evoked glutamate transporter EAAT5 activation coordinates with conventional feedback inhibition to control rod bipolar cell output.

In the retina, modulation of the amplitude of dim visual signals primarily occurs at axon terminals of rod bipolar cells (RBCs). GABA and glycine inhibitory neurotransmitter receptors and the excitatory amino acid transporter 5 (EAAT5) modulate the RBC output. EAATs clear glutamate from the synapse, but they also have a glutamate-gated chloride conductance.

Differential encoding of spatial information among retinal on cone bipolar cells.

The retina is the first stage of visual processing. It encodes elemental features of visual scenes. Distinct cone bipolar cells provide the substrate for this to occur.

Developmental regulation and activity-dependent maintenance of GABAergic presynaptic inhibition onto rod bipolar cell axonal terminals.

Presynaptic inhibition onto axons regulates neuronal output, but how such inhibitory synapses develop and are maintained in vivo remains unclear. Axon terminals of glutamatergic retinal rod bipolar cells (RBCs) receive GABAA and GABAC receptor-mediated synaptic inhibition. We found that perturbing GABAergic or glutamatergic neurotransmission does not prevent GABAergic synaptogenesis onto RBC axons.

The mode of retinal presynaptic inhibition switches with light intensity.

Excitatory amino acid transporters (EAATs) terminate signaling in the CNS by clearing released glutamate. Glutamate also evokes an EAAT-mediated Cl(-) current, but its role in CNS signaling is poorly understood. We show in mouse retina that EAAT-mediated Cl(-) currents that were evoked by light inhibit rod pathway signaling.

Nonlinear interactions between excitatory and inhibitory retinal synapses control visual output.

The visual system is highly sensitive to dynamic features in the visual scene. However, it is not known how or where this enhanced sensitivity first occurs. We investigated this phenomenon by studying interactions between excitatory and inhibitory synapses in the second synaptic layer of the mouse retina.

G-protein betagamma-complex is crucial for efficient signal amplification in vision.

A fundamental question of cell signaling biology is how faint external signals produce robust physiological responses. One universal mechanism relies on signal amplification via intracellular cascades mediated by heterotrimeric G-proteins. This high amplification system allows retinal rod photoreceptors to detect single photons of light.

Multiple pathways of inhibition shape bipolar cell responses in the retina.

Bipolar cells (BCs) are critical relay neurons in the retina that are organized into parallel signaling pathways. The three main signaling pathways in the mammalian retina are the rod, ON cone, and OFF cone BCs. Rod BCs mediate incrementing dim light signals from rods, and ON cone and OFF cone BCs mediate incrementing and decrementing brighter light signals from cones, respectively.

Interneuron circuits tune inhibition in retinal bipolar cells.

While connections between inhibitory interneurons are common circuit elements, it has been difficult to define their signal processing roles because of the inability to activate these circuits using natural stimuli. We overcame this limitation by studying connections between inhibitory amacrine cells in the retina. These interneurons form spatially extensive inhibitory networks that shape signaling between bipolar cell relay neurons to ganglion cell output neurons.

Development of presynaptic inhibition onto retinal bipolar cell axon terminals is subclass-specific.

Synaptic integration is modulated by inhibition onto the dendrites of postsynaptic cells. However, presynaptic inhibition at axonal terminals also plays a critical role in the regulation of neurotransmission. In contrast to the development of inhibitory synapses onto dendrites, GABAergic/glycinergic synaptogenesis onto axon terminals has not been widely studied.

Nyctalopin expression in retinal bipolar cells restores visual function in a mouse model of complete X-linked congenital stationary night blindness.

Mutations in the NYX gene that encodes the protein nyctalopin cause congenital stationary night blindness type 1. In no b-wave (nob) mice, a mutation in Nyx results in a functional phenotype that includes the absence of the electroretinogram b-wave and abnormal spontaneous and light-evoked activity in retinal ganglion cells (RGCs). In contrast, there is no morphological abnormality in the retina at either the light or electron microscopic levels.

Carbonic anhydrase XIV deficiency produces a functional defect in the retinal light response.

Members of the carbonic anhydrase (CA) family play an important role in the regulation of pH, CO(2), ion, and water transport. CA IV and CA XIV are membrane-bound isozymes expressed in the eye. CA IV immunostaining is limited to the choriocapillaris overlying the retina, whereas CA XIV is expressed within the retina in Müller glial cells and retinal pigment epithelium.

Presynaptic inhibition differentially shapes transmission in distinct circuits in the mouse retina.

Diverse retinal outputs are mediated by ganglion cells that receive excitatory input from distinct classes of bipolar cells (BCs). These classes of BCs separate visual signals into rod, ON and OFF cone pathways. Although BC signalling is a major determinant of the ganglion cell-mediated retinal output, it is not fully understood how light-evoked, presynaptic inhibition from amacrine cell inputs shapes BC outputs.

Ambient light regulates sodium channel activity to dynamically control retinal signaling.

The retinal network increases its sensitivity in low-light conditions to detect small visual inputs and decreases its sensitivity in bright-light conditions to prevent saturation. However, the cellular mechanisms that adjust visual signaling in the retinal network are not known. Here, we show that voltage-gated sodium channels in bipolar cells dynamically control retinal light sensitivity.

Receptor and transmitter release properties set the time course of retinal inhibition.

Synaptic inhibition is determined by the properties of postsynaptic receptors, neurotransmitter release, and clearance, but little is known about how these factors shape sensation-evoked inhibition. The retina is an ideal system to investigate inhibition because it can be activated physiologically with light, and separate inhibitory pathways can be assayed by recording from rod bipolar cells that possess distinct glycine, GABA(A), and GABA(C) receptors (R). We show that receptor properties differentially shape spontaneous IPSCs, whereas both transmitter release and receptor properties shape light-evoked (L) IPSCs.

Presynaptic inhibition modulates spillover, creating distinct dynamic response ranges of sensory output.

Sensory information is thought to be modulated by presynaptic inhibition. Although this form of inhibition is a well-studied phenomenon, it is still unclear what role it plays in shaping sensory signals in intact circuits. By visually stimulating the retinas of transgenic mice lacking GABAc receptor-mediated presynaptic inhibition, we found that this inhibition regulated the dynamic range of ganglion cell (GC) output to the brain.

GABA(A), GABA(C) and glycine receptor-mediated inhibition differentially affects light-evoked signalling from mouse retinal rod bipolar cells.

Rod bipolar cells relay visual signals evoked by dim illumination from the outer to the inner retina. GABAergic and glycinergic amacrine cells contact rod bipolar cell terminals, where they modulate transmitter release and contribute to the receptive field properties of third order neurones. However, it is not known how these distinct inhibitory inputs affect rod bipolar cell output and subsequent retinal processing.

Inner and outer retinal pathways both contribute to surround inhibition of salamander ganglion cells.

Illumination of the receptive-field surround reduces the sensitivity of a retinal ganglion cell to centre illumination. The steady, antagonistic receptive-field surround of retinal ganglion cells is classically attributed to the signalling of horizontal cells in the outer plexiform layer (OPL). However, amacrine cell signalling in the inner plexiform layer (IPL) also contributes to the steady receptive-field surround of the ganglion cell.

Sodium channels in transient retinal bipolar cells enhance visual responses in ganglion cells.

Retinal bipolar cells are slow potential neurons that respond to photoreceptor inputs with graded potentials and do not fire action potentials. We found that transient ON bipolar cells recorded in retinal slices possess voltage-gated sodium channels located on either their dendrites or somas. The sodium currents in these neurons did not generate spikes but enhanced voltage responses evoked by visual stimulation, which selectively boosted transmission to transient ganglion cells.

Synaptic mechanisms that shape visual signaling at the inner retina.

The retina is a layered structure that processes information in two stages. The outer plexiform layer (OPL) comprises the first stage and is where photoreceptors, bipolar cells, and horizontal cells interact synaptically. This is the synaptic layer where ON and OFF responses to light are formed, as well as the site where receptive field center and surround organization is first thought to occur.

GABAC receptor-mediated inhibition in the retina.

Inhibition at bipolar cell axon terminals regulates excitatory signaling to ganglion cells and is mediated, in part, by GABAC receptors. We investigated GABAC receptor-mediated inhibition using pharmacological approaches and genetically altered mice that lack GABAC receptors. Responses to applied GABA showed distinct time courses in various bipolar cell classes, attributable to different proportions of GABAA and GABAC receptors.

Spike-dependent GABA inputs to bipolar cell axon terminals contribute to lateral inhibition of retinal ganglion cells.

The inhibitory surround signal in retinal ganglion cells is usually attributed to lateral horizontal cell signaling in the outer plexiform layer (OPL). However, recent evidence suggests that lateral inhibition at the inner plexiform layer (IPL) also contributes to the ganglion cell receptive field surround. Although amacrine cell input to ganglion cells mediates a component of this lateral inhibition, it is not known if presynaptic inhibition to bipolar cell terminals also contributes to surround signaling.

Activation of group II metabotropic glutamate receptors inhibits glutamate release from salamander retinal photoreceptors.

We investigated the effects of group II metabotropic glutamate receptor (mGluR) activation on excitatory synaptic transmission in the salamander retinal slice preparation. The group II selective agonists DCG-IV and LY354740 reduced light-evoked excitatory postsynaptic currents (EPSCs) in ganglion cells. To determine the synaptic basis of this effect, we also recorded from bipolar cells and horizontal cells.

Elimination of the rho1 subunit abolishes GABA(C) receptor expression and alters visual processing in the mouse retina.

Inhibition is crucial for normal function in the nervous system. In the CNS, inhibition is mediated primarily by the amino acid GABA via activation of two ionotropic GABA receptors, GABA(A) and GABA(C). GABA(A) receptor composition and function have been well characterized, whereas much less is known about native GABA(C) receptors.

GABA transporters regulate inhibition in the retina by limiting GABA(C) receptor activation.

Inhibition is mediated by two classes of ionotropic receptors in the retina, GABA(A) and GABA(C) receptors. We used the GABA transport blocker NO-711 to examine the role of GABA transporters in shaping synaptic responses mediated by these two receptors in the salamander retinal slice preparation. Focal applications (puffs) of GABA onto GABA(C) receptors on bipolar cells terminals or GABA(A) receptors on ganglion cells elicited currents that were enhanced by NO-711, demonstrating the presence of transporters in the inner plexiform layer (IPL).