Dopaminergic amacrine cells express opioid receptors in the mouse retina

AbstractThe presence of opioid receptors has been confirmed by a variety of techniques in vertebrate retinas including those of mammals; however, in most reports, the location of these receptors has been limited to retinal regions rather than specific cell types. Concurrently, our knowledge of the physiological functions of opioid signaling in the retina is based on only a handful of studies. To date, the best-documented opioid effect is the modulation of retinal dopamine release, which has been shown in a variety of vertebrate species. Nonetheless, it is not known if opioids can affect dopaminergic amacrine cells (DACs) directly, via opioid receptors expressed by DACs. This study, using immunohistochemical methods, sought to determine whether (1) μ- and δ-opioid receptors (MORs and DORs, respectively) are present in the mouse retina, and if present, (2) are they expressed by DACs. We found that MOR and DOR immunolabeling were associated with multiple cell types in the inner retina, suggesting that opioids might influence visual information processing at multiple sites within the mammalian retinal circuitry. Specifically, colabeling studies with the DAC molecular marker anti-tyrosine hydroxylase antibody showed that both MOR and DOR immunolabeling localize to DACs. These findings predict that opioids can affect DACs in the mouse retina directly, via MOR and DOR signaling, and might modulate dopamine release as reported in other mammalian and nonmammalian retinas.

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Functional localization of the nitric oxide/cGMP pathway in the salamander retina

Visual Neuroscience ◽

10.1017/s0952523809990125 ◽

2009 ◽

Vol 26 (3) ◽

pp. 275-286 ◽

Cited By ~ 10

Author(s):

JAN J. BLOM ◽

TODD A. BLUTE ◽

WILLIAM D. ELDRED

Keyword(s):

Nitric Oxide ◽

Signaling Pathway ◽

Visual Information ◽

Amacrine Cells ◽

Cell Types ◽

Guanosine Monophosphate ◽

Specific Cell ◽

No Production ◽

Outer Retina ◽

Cgmp Pathway

AbstractNitric oxide (NO) is a gaseous neuromodulator that has physiological functions in every cell type in the retina. Evidence indicates that NO often plays a role in the processing of visual information in the retina through the second messenger cyclic guanosine monophosphate (cGMP). Despite numerous structural and functional studies of this signaling pathway in the retina, none have examined many of the elements of this pathway within a single study in a single species. In this study, the NO/cGMP pathway was localized to specific regions and cell types within the inner and outer retina. We have immunocytochemically localized nitric oxide synthase, the enzyme that produces NO, in photoreceptor ellipsoids, four distinct classes of amacrine cells, Müller and bipolar cells, somata in the ganglion cell layer, as well as in processes within both plexiform layers. Additionally, we localized NO production in specific cell types using the NO-sensitive dye diaminofluorescein. cGMP immunocytochemistry was used to functionally localize soluble guanylate cyclase that was activated by an NO donor in select amacrine and bipolar cell classes. Analysis of cGMP and its downstream target, cGMP-dependent protein kinase II (PKGII), showed colocalization within processes in the outer retina as well as in somata in the inner retina. The results of this study showed that the NO/cGMP signaling pathway was functional and its components were widely distributed throughout specific cell types in the outer and inner salamander retina.

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Nitric Oxide Transiently Converts Synaptic Inhibition to Excitation in Retinal Amacrine Cells

Journal of Neurophysiology ◽

10.1152/jn.01317.2005 ◽

2006 ◽

Vol 95 (5) ◽

pp. 2866-2877 ◽

Cited By ~ 27

Author(s):

Brian Hoffpauir ◽

Emily McMains ◽

Evanna Gleason

Keyword(s):

Nitric Oxide ◽

Hippocampal Neurons ◽

Reversal Potential ◽

Amacrine Cells ◽

Cell Types ◽

Synaptic Function ◽

Positive Shift ◽

Gabaergic Synapses ◽

Multiple Cell

Nitric oxide (NO) is generated by multiple cell types in the vertebrate retina, including amacrine cells. We investigate the role of NO in the modulation of synaptic function using a culture system containing identified retinal amacrine cells. We find that moderate concentrations of NO alter GABAA receptor function to produce an enhancement of the GABA-gated current. Higher concentrations of NO also enhance GABA-gated currents, but this enhancement is primarily due to a substantial positive shift in the reversal potential of the current. Several pieces of evidence, including a similar effect on glycine-gated currents, indicate that the positive shift is due to an increase in cytosolic Cl−. This change in the chloride distribution is especially significant because it can invert the sign of GABA- and glycine-gated voltage responses. Furthermore, current- and voltage-clamp recordings from synaptic pairs of GABAergic amacrine cells demonstrate that NO transiently converts signaling at GABAergic synapses from inhibition to excitation. Persistence of the NO-induced shift in ECl− in the absence of extracellular Cl− indicates that the increase in cytosolic Cl− is due to release of Cl− from an internal store. An NO-dependent release of Cl− from an internal store is also demonstrated for rat hippocampal neurons indicating that this mechanism is not restricted to the avian retina. Thus signaling in the CNS can be fundamentally altered by an NO-dependent mobilization of an internal Cl− store.

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Synaptic inhibition tunes contrast computation in the retina

Visual Neuroscience ◽

10.1017/s095252381900004x ◽

2019 ◽

Vol 36 ◽

Cited By ~ 3

Author(s):

Nicholas W. Oesch ◽

Jeffrey S. Diamond

Keyword(s):

Visual Information ◽

Amacrine Cells ◽

Cell Types ◽

Inhibitory Interneuron ◽

Inhibitory Synapses ◽

Gabaergic Interneuron ◽

Primary Role ◽

Temporal Contrast ◽

Synaptic Receptors ◽

Different Cell Types

AbstractInhibition shapes activity and signal processing in neural networks through numerous mechanisms mediated by many different cell types. Here, we examined how one type of GABAergic interneuron in the retina, the A17 amacrine cell, influences visual information processing. Our results suggest that A17s, which make reciprocal feedback inhibitory synapses onto rod bipolar cell (RBC) synaptic terminals, extend the luminance range over which RBC synapses compute temporal contrast and enhance the reliability of contrast signals over this range. Inhibition from other amacrine cells does not influence these computational features. Although A17-mediated feedback is mediated by both GABAA and GABAC receptors, the latter plays the primary role in extending the range of contrast computation. These results identify specific functions for an inhibitory interneuron subtype, as well as specific synaptic receptors, in a behaviorally relevant neural computation.

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Complex Cell Type-Specific Roles of Autophagy in Liver Fibrosis and Cirrhosis

Pathogens ◽

10.3390/pathogens9030225 ◽

2020 ◽

Vol 9 (3) ◽

pp. 225

Author(s):

Tzu-Min Hung ◽

Chih-Chiang Hsiao ◽

Chih-Wen Lin ◽

Po-Huang Lee

Keyword(s):

Liver Fibrosis ◽

Cell Types ◽

Degradation Pathway ◽

Cellular Tissue ◽

Future Research ◽

Specific Cell ◽

Cell Type ◽

Stage Disease ◽

Multiple Cell ◽

End Stage

The lysosomal degradation pathway, or autophagy, plays a fundamental role in cellular, tissue, and organismal homeostasis. A correlation between dysregulated autophagy and liver fibrosis (including end-stage disease, cirrhosis) is well-established. However, both the up and downregulation of autophagy have been implicated in fibrogenesis. For example, the inhibition of autophagy in hepatocytes and macrophages can enhance liver fibrosis, whereas autophagic activity in hepatic stellate cells and reactive ductular cells is permissive towards fibrogenesis. In this review, the contributions of specific cell types to liver fibrosis as well as the mechanisms underlying the effects of autophagy are summarized. In view of the functional effects of multiple cell types on the complex process of hepatic fibrogenesis, integrated approaches that consider the role of autophagy in each liver cell type should be a focus of future research.

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Laminin deficits induce alterations in the development of dopaminergic neurons in the mouse retina

Visual Neuroscience ◽

10.1017/s0952523807070514 ◽

2007 ◽

Vol 24 (4) ◽

pp. 549-562 ◽

Cited By ~ 27

Author(s):

VIKTÓRIA DÉNES ◽

PAUL WITKOVSKY ◽

MANUEL KOCH ◽

DALE D. HUNTER ◽

GERMÁN PINZÓN-DUARTE ◽

...

Keyword(s):

Amacrine Cells ◽

Cell Types ◽

Mouse Retina ◽

Null Mouse ◽

Type I ◽

Intermediate Cell ◽

Retinal Ganglion ◽

Wild Type ◽

Müller Glial Cell ◽

Process Outgrowth

Genetically modified mice lacking the β2 laminin chain (β2null), the γ3 laminin chain (γ3 null), or both β2/γ3 chains (compound null) were produced. The development of tyrosine hydroxylase (TH) immunoreactive neurons in these mouse lines was studied between birth and postnatal day (P) 20. Compared to wild type mice, no alterations were seen in γ3 null mice. In β2 null mice, however, the large, type I TH neurons appeared later in development, were at a lower density and had reduced TH immunoreactivity, although TH process number and size were not altered. In the compound null mouse, the same changes were observed together with reduced TH process outgrowth. Surprisingly, in the smaller, type II TH neurons, TH immunoreactivity was increased in laminin-deficient compared to wild type mice. Other retinal defects we observed were a patchy disruption of the inner limiting retinal basement membrane and a disoriented growth of Müller glial cells. Starburst and AII type amacrine cells were not apparently altered in laminin-deficient relative to wild type mice. We postulate that laminin-dependent developmental signals are conveyed to TH amacrine neurons through intermediate cell types, perhaps the Müller glial cell and/or the retinal ganglion cell.

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DSCAM and DSCAML1 Function in Self-Avoidance in Multiple Cell Types in the Developing Mouse Retina

Neuron ◽

10.1016/j.neuron.2009.09.027 ◽

2009 ◽

Vol 64 (4) ◽

pp. 484-497 ◽

Cited By ~ 138

Author(s):

Peter G. Fuerst ◽

Freyja Bruce ◽

Miao Tian ◽

Wei Wei ◽

Justin Elstrott ◽

...

Keyword(s):

Cell Types ◽

Mouse Retina ◽

Multiple Cell

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Local processing in neurites of VGluT3-expressing amacrine cells differentially organizes visual information

eLife ◽

10.7554/elife.31307 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 3

Author(s):

Jen-Chun Hsiang ◽

Keith P Johnson ◽

Linda Madisen ◽

Hongkui Zeng ◽

Daniel Kerschensteiner

Keyword(s):

Visual Processing ◽

Visual Information ◽

Receptive Fields ◽

Visual Space ◽

Amacrine Cells ◽

Object Motion ◽

Image Motion ◽

Local Processing ◽

Mouse Retina ◽

Population Activity

Neurons receive synaptic inputs on extensive neurite arbors. How information is organized across arbors and how local processing in neurites contributes to circuit function is mostly unknown. Here, we used two-photon Ca2+ imaging to study visual processing in VGluT3-expressing amacrine cells (VG3-ACs) in the mouse retina. Contrast preferences (ON vs. OFF) varied across VG3-AC arbors depending on the laminar position of neurites, with ON responses preferring larger stimuli than OFF responses. Although arbors of neighboring cells overlap extensively, imaging population activity revealed continuous topographic maps of visual space in the VG3-AC plexus. All VG3-AC neurites responded strongly to object motion, but remained silent during global image motion. Thus, VG3-AC arbors limit vertical and lateral integration of contrast and location information, respectively. We propose that this local processing enables the dense VG3-AC plexus to contribute precise object motion signals to diverse targets without distorting target-specific contrast preferences and spatial receptive fields.

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Molecular identification of sixty-three amacrine cell types completes a mouse retinal cell atlas

10.1101/2020.03.10.985770 ◽

2020 ◽

Cited By ~ 2

Author(s):

Wenjun Yan ◽

Mallory A. Laboulaye ◽

Nicholas M. Tran ◽

Irene E. Whitney ◽

Inbal Benhar ◽

...

Keyword(s):

Transcription Factors ◽

Single Cell ◽

High Throughput ◽

Amacrine Cells ◽

Cell Types ◽

Retinal Cell ◽

Mouse Retina ◽

Single Cell Rna Sequencing ◽

Neuronal Types ◽

The Brain

ABSTRACTAmacrine cells (ACs) are a diverse class of interneurons that modulate input from photoreceptors to retinal ganglion cells (RGCs), rendering each RGC type selectively sensitive to particular visual features, which are then relayed to the brain. While many AC types have been identified morphologically and physiologically, they have not been comprehensively classified or molecularly characterized. We used high-throughput single-cell RNA sequencing (scRNA-seq) to profile >32,000 ACs from mouse retina, and applied computational methods to identify 63 AC types. We identified molecular markers for each type, and used them to characterize the morphology of multiple types. We show that they include nearly all previously known AC types as well as many that had not been described. Consistent with previous studies, most of the AC types express markers for the canonical inhibitory neurotransmitters GABA or glycine, but several express neither or both. In addition, many express one or more neuropeptides, and two express glutamatergic markers. We also explored transcriptomic relationships among AC types and identified transcription factors expressed by individual or multiple closely related types. Noteworthy among these were Meis2 and Tcf4, expressed by most GABAergic and most glycinergic types, respectively. Together, these results provide a foundation for developmental and functional studies of ACs, as well as means for genetically accessing them. Along with previous molecular, physiological and morphological analyses, they establish the existence of at least 130 neuronal types and nearly 140 cell types in mouse retina.SIGNIFICANCE STATEMENTThe mouse retina is a leading model for analyzing the development, structure, function and pathology of neural circuits. A complete molecular atlas of retinal cell types provides an important foundation for these studies. We used high-throughput single-cell RNA sequencing (scRNA-seq) to characterize the most heterogeneous class of retinal interneurons, amacrine cells, identifying 63 distinct types. The atlas includes types identified previously as well as many novel types. We provide evidence for use of multiple neurotransmitters and neuropeptides and identify transcription factors expressed by groups of closely related types. Combining these results with those obtained previously, we proposed that the mouse retina contains 130 neuronal types, and is therefore comparable in complexity to other regions of the brain.

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Probe-Seq enables transcriptional profiling of specific cell types from heterogeneous tissue by RNA-based isolation

10.1101/735738 ◽

2019 ◽

Author(s):

Ryoji Amamoto ◽

Mauricio D. Garcia ◽

Emma R. West ◽

Jiho Choi ◽

Sylvain W. Lapan ◽

...

Keyword(s):

Transcriptional Profiling ◽

Cell Types ◽

Cell Populations ◽

Specific Cell ◽

Rna Profiling ◽

Complementary Method ◽

Dissociated Cells ◽

Multiple Cell ◽

Heterogeneous Tissue

ABSTRACTRecent transcriptional profiling technologies are uncovering previously-undefined cell populations and molecular markers at an unprecedented pace. While single cell RNA (scRNA) sequencing is an attractive approach for unbiased transcriptional profiling of all cell types, a complementary method to isolate and sequence specific cell populations from heterogeneous tissue remains challenging. Here, we developed Probe-Seq, which allows deep transcriptional profiling of specific cell types isolated using RNA as the defining feature. Dissociated cells are labelled using fluorescent in situ hybridization (FISH) for RNA, and then isolated by fluorescent activated cell sorting (FACS). We used Probe-Seq to purify and profile specific cell types from mouse, human, and chick retinas, as well as the Drosophila midgut. Probe-Seq is compatible with frozen nuclei, making cell types within archival tissue immediately accessible. As it can be multiplexed, combinations of markers can be used to create specificity. Multiplexing also allows for the isolation of multiple cell types from one cell preparation. Probe-Seq should enable RNA profiling of specific cell types from any organism.

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Dendro-somatic synaptic inputs to ganglion cells violate receptive field and connectivity rules in the mammalian retina

10.1101/2021.07.01.450751 ◽

2021 ◽

Author(s):

Miloslav Sedlacek ◽

William Grimes ◽

Morgan Musgrove ◽

Amurta Nath ◽

Hua Tian ◽

...

Keyword(s):

Receptive Field ◽

Ganglion Cells ◽

Plexiform Layer ◽

Amacrine Cells ◽

Cell Types ◽

Excitatory Input ◽

Mouse Retina ◽

Inner Plexiform Layer ◽

Visual Response ◽

Dendritic Arbors

In retinal neurons, morphology strongly influences visual response features. Ganglion cell (GC) dendrites ramify in distinct strata of the inner plexiform layer (IPL) so that GCs responding to light increments (ON) or decrements (OFF) receive appropriate excitatory inputs. This vertical stratification prescribes response polarity and ensures consistent connectivity between cell types, whereas the lateral extent of GC dendritic arbors typically dictates receptive field (RF) size. Here, we identify circuitry in mouse retina that contradicts these conventions. A2 amacrine cells are interneurons understood to mediate 'cross-over' inhibition by relaying excitatory input from the ON layer to inhibitory outputs in the OFF layer. Ultrastructural and physiological analyses show, however, that some A2s deliver powerful inhibition to OFF GC somas and proximal dendrites in the ON layer, rendering their inhibitory RFs smaller than their dendritic arbors. This OFF pathway, avoiding entirely the OFF region of the IPL, challenges several tenets of retinal circuitry.

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