Mechanisms Underlying Lateral GABAergic Feedback onto Rod Bipolar Cells in Rat Retina

Chávez, Andrés E.; Grimes, William N.; Diamond, Jeffrey S.

doi:10.1523/jneurosci.5574-09.2010

Cited by 85 publications

(135 citation statements)

References 81 publications

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“…Both GABA A -and GABA C Rs on RBC synaptic terminals can be activated by reciprocal feedback inhibition under various conditions (Chavez et al 2010;Eggers and Lukasiewicz 2006a,b;Hartveit 1999), but the subsynaptic localization of the two receptor types relative to each other remains unclear. EM indicates that both receptor subtypes are localized to RBC-A17 synapses (Fletcher and Wassle 1999), but double-label immunofluorescence data suggest that two subtypes are typically not colocalized at the same synapses (Fletcher et al 1998;Frazao et al 2007).…”

Section: Structural and Molecular Assessment Of The Microcircuitmentioning

confidence: 99%

“…Previous work has shown that, when reciprocal feedback is elicited by depolarizing a single RBC under whole cell voltage clamp, the feedback inhibitory postsynaptic current (IPSC) is mediated primarily by GABA A Rs (Chavez et al 2010;Singer and Diamond 2003). When synaptic activation of A17s is enhanced, either by blocking postsynaptic receptor desensitization or by augmenting release from RBCs, a GABA C R-mediated component emerges in the feedback IPSC (Chavez et al 2010;Hartveit 1999;Singer and Diamond 2003). The anatomical data presented in Fig.…”

Section: Structural and Molecular Assessment Of The Microcircuitmentioning

confidence: 99%

“…Examining the role of A17-mediated reciprocal feedback inhibition in signaling evoked by single photons is complicated by the fact that GABARs also mediate inhibitory inputs onto RBCs from other amacrine cells (Chavez et al 2010;Eggers and Lukasiewicz 2006a) as well as inhibition between amacrine cells (Eggers and Lukasiewicz 2010). The effect of blocking either GABA A Rs or GABA C Rs would, therefore, be ambiguous under physiological conditions.…”

Section: Structural and Molecular Assessment Of The Microcircuitmentioning

confidence: 99%

“…Instead, we tested the effects of DHT, the A17-specific toxin ( Fig. 3F; see METHODS) (Chavez et al 2006(Chavez et al , 2010Dong and Hare 2003). Flashes were chosen to be just detectable (SNR ϳ0.5) while minimizing contamination from coincident SPRs traversing individual RBCs (Fig.…”

Section: Structural and Molecular Assessment Of The Microcircuitmentioning

confidence: 99%

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Complex inhibitory microcircuitry regulates retinal signaling near visual threshold

Grimes

Zhang

Tian

et al. 2015

Journal of Neurophysiology

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Neuronal microcircuits, small, localized signaling motifs involving two or more neurons, underlie signal processing and computation in the brain. Compartmentalized signaling within a neuron may enable it to participate in multiple, independent microcircuits. Each A17 amacrine cell in the mammalian retina contains within its dendrites hundreds of synaptic feedback microcircuits that operate independently to modulate feedforward signaling in the inner retina. Each of these microcircuits comprises a small (<1 μm) synaptic varicosity that typically receives one excitatory synapse from a presynaptic rod bipolar cell (RBC) and returns two reciprocal inhibitory synapses back onto the same RBC terminal. Feedback inhibition from the A17 sculpts the feedforward signal from the RBC to the AII, a critical component of the circuitry mediating night vision. Here, we show that the two inhibitory synapses from the A17 to the RBC express kinetically distinct populations of GABA receptors: rapidly activating GABA(A)Rs are enriched at one synapse while more slowly activating GABA(C)Rs are enriched at the other. Anatomical and electrophysiological data suggest that macromolecular complexes of voltage-gated (Cav) channels and Ca(2+)-activated K(+) channels help to regulate GABA release from A17 varicosities and limit GABA(C)R activation under certain conditions. Finally, we find that selective elimination of A17-mediated feedback inhibition reduces the signal to noise ratio of responses to dim flashes recorded in the feedforward pathway (i.e., the AII amacrine cell). We conclude that A17-mediated feedback inhibition improves the signal to noise ratio of RBC-AII transmission near visual threshold, thereby improving visual sensitivity at night.

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Section: Structural and Molecular Assessment Of The Microcircuitmentioning

confidence: 99%

Section: Structural and Molecular Assessment Of The Microcircuitmentioning

confidence: 99%

Section: Structural and Molecular Assessment Of The Microcircuitmentioning

confidence: 99%

Section: Structural and Molecular Assessment Of The Microcircuitmentioning

confidence: 99%

See 2 more Smart Citations

Complex inhibitory microcircuitry regulates retinal signaling near visual threshold

Grimes

Zhang

Tian

et al. 2015

Journal of Neurophysiology

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“…In the VIAAT KO, GABA A α1 at synapses onto BC axons is down-regulated whereas its expression on the dendrites is up-regulated. Furthermore, different ionotropic GABA receptor types (GABA A and GABA C ) clustered at nonoverlapping sites (33,34) but opposite the same presynaptic A17 amacrine cell bouton (35) are similarly downregulated in the VIAAT KO. Together, these observations imply that activity-dependent regulation of inhibitory receptors is input type-specific.…”

Section: Activity-dependent Regulation Of Inhibitory Receptor Expressionmentioning

confidence: 96%

Neurotransmission plays contrasting roles in the maturation of inhibitory synapses on axons and dendrites of retinal bipolar cells

Hoon

Sinha

Okawa

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Neuronal output is modulated by inhibition onto both dendrites and axons. It is unknown whether inhibitory synapses at these two cellular compartments of an individual neuron are regulated coordinately or separately during in vivo development. Because neurotransmission influences synapse maturation and circuit development, we determined how loss of inhibition affects the expression of diverse types of inhibitory receptors on the axon and dendrites of mouse retinal bipolar cells. We found that axonal GABA but not glycine receptor expression depends on neurotransmission. Importantly, axonal and dendritic GABA A receptors comprise distinct subunit compositions that are regulated differentially by GABA release: Axonal GABA A receptors are down-regulated but dendritic receptors are up-regulated in the absence of inhibition. The homeostatic increase in GABA A receptors on bipolar cell dendrites is pathway-specific: Cone but not rod bipolar cell dendrites maintain an up-regulation of receptors in the transmission deficient mutants. Furthermore, the bipolar cell GABA A receptor alterations are a consequence of impaired vesicular GABA release from amacrine but not horizontal interneurons. Thus, inhibitory neurotransmission regulates in vivo postsynaptic maturation of inhibitory synapses with contrasting modes of action specific to synapse type and location.GABA receptor | retina | synaptic inhibition | axon-dendrite I nterneurons of the CNS control neuronal excitability through release of γ-aminobutyric acid (GABA) and glycine. How inhibition modifies neuronal output depends largely on the types of presynaptic interneurons making synapses onto a postsynaptic cell, and the location and densities of these synapses (1-3). Moreover, inhibitory receptor types with distinct transmitter affinities and kinetics present on the axon or dendrites of an individual neuron can critically shape its output (3-6). Although much is known about how different inhibitory synapses shape the spatiotemporal activity patterns of mature neurons, it is less clear what factors regulate the expression of inhibitory receptors at these synapses during development in vivo. Is the expression of distinct inhibitory receptor types within a cellular compartment (axon or dendrite) regulated coordinately or independently? Conversely, is the expression of the same receptor type at different cellular compartments of an individual neuron regulated by common or separate factors?To answer these questions, we assessed expression of inhibitory receptors on the axon and dendrites of individual glutamatergic retinal neurons in mice with genetically suppressed inhibition. We generated retina-specific knockouts of the vesicular inhibitory amino acid transporter (VIAAT), which mediates uptake of GABA or glycine into synaptic vesicles (7,8). We perturbed inhibition because it has been found previously to influence pre-and postsynaptic maturation of GABAergic synapses (9-12). However, whether inhibitory receptor expression at the "input" and "output" compartments of an in...

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Rod‐cone crossover connectome of mammalian bipolar cells

Lauritzen

Sigulinsky

Anderson

et al. 2016

J of Comparative Neurology

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The basis of cross-suppression between rod and cone channels has long been an enigma. Using rabbit retinal connectome RC1, we show that all cone bipolar cell (BC) classes inhibit rod BCs via amacrine cell (AC) motifs (C1–6); that all cone BC classes are themselves inhibited by AC motifs (R1–5, R25) driven by rod BCs. A sparse symmetric AC motif (CR) is presynaptic and postsynaptic to both rod and cone BCs. ON cone BCs of all classes drive inhibition of rod BCs via motif C1 wide-field GABAergic ACs (γACs) and motif C2 narrow field glycinergic ON ACs (GACs). Each rod BC receives ≈ 10 crossover AC synapses and each ON cone BC can target ≈10 or more rod BCs via separate AC processes. OFF cone BCs mediate monosynaptic inhibition of rod BCs via motif C3 driven by OFF γACs and GACs and disynaptic inhibition via motifs C4 and C5 driven by OFF wide-field γACs and narrow-field GACs, respectively. Motifs C4 and C5 form halos of 60–100 inhibitory synapses on proximal dendrites of AI γACs. Rod BCs inhibit surrounding arrays of cone BCs through AII GAC networks that access ON and OFF cone BC patches via motifs R1, R2, R4, R5 and a unique ON AC motif R3 that collects rod BC inputs and targets ON cone BCs. Crossover synapses for motifs C1, C4, C5, and R3 are 3–4× larger than typical feedback synapses, which may be a signature for synaptic winner-take-all switches.

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Mechanisms Underlying Lateral GABAergic Feedback onto Rod Bipolar Cells in Rat Retina

Cited by 85 publications

References 81 publications

Complex inhibitory microcircuitry regulates retinal signaling near visual threshold

Complex inhibitory microcircuitry regulates retinal signaling near visual threshold

Neurotransmission plays contrasting roles in the maturation of inhibitory synapses on axons and dendrites of retinal bipolar cells

Rod‐cone crossover connectome of mammalian bipolar cells

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