Gbx2 identifies two amacrine cell subtypes with distinct molecular, morphological, and physiological properties

ABSTRACTOur understanding of how the nervous sytem works is limited by our ability to identify the neuronal subtypes that comprise functional circuits. Using a genetic approach, we show that the transcription factor Gbx2 labels two amacrine cell (AC) subtypes in the mouse retina that have distinct morphological, physiological, and molecular properties. One subtype of Gbx2+ ACs are likely the previously characterized On-type GABAergic CRH-1 AC. The other Gbx2+ AC population is a previously uncharacterized non-GABAergic, non-Glycinergic (nGnG) AC subtype. Gbx2+ nGnG ACs are On-Off type cells with asymmetric dendritic arbors. Gbx2+ nGnG ACs also exhibit tracer coupling to bipolar cells (BCs) through gap junctions that are modulated by dopamine signaling. This study genetically identifies a previously uncharacterized AC subtype and reveals an unusual AC-BC connectivity through gap junctions that may provide a novel model of synaptic communication and visual circuit function.

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Heterocellular coupling between amacrine cell and ganglion cells

10.1101/328815 ◽

2018 ◽

Author(s):

Robert E. Marc ◽

Crystal Sigulinsky ◽

Rebecca L. Pfeiffer ◽

Daniel Emrich ◽

James R. Anderson ◽

...

Keyword(s):

Gap Junctions ◽

Ganglion Cell ◽

Bipolar Cell ◽

Amacrine Cell ◽

Ganglion Cells ◽

Plexiform Layer ◽

Amacrine Cells ◽

Bipolar Cells ◽

Inner Plexiform Layer ◽

Tem Analysis

AbstractAll superclasses of retinal neurons display some form of electrical coupling including the key neurons of the inner plexiform layer: bipolar cells (BCs), amacrine or axonal cells (ACs) and ganglion cells (GCs). However, coupling varies extensively by class. For example, mammalian rod bipolar cells form no gap junctions at all, while all cone bipolar cells form class-specific coupling arrays, many of them homocellular in-superclass arrays. Ganglion cells are unique in that classes with coupling predominantly form heterocellular cross-class arrays of ganglion cell::amacrine cell (GC::AC) coupling in the mammalian retina. Ganglion cells are the least frequent superclass in the inner plexiform layer and GC::AC gap junctions are sparsely arrayed amidst massive cohorts of AC::AC, bipolar cell BC::BC, and AC::BC gap junctions. Many of these gap junctions and most ganglion cell gap junctions are suboptical, complicating analysis of specific ganglion cells. High resolution 2 nm TEM analysis of rabbit retinal connectome RC1 allows quantitative GC::AC coupling maps of identified ganglion cells. Ganglion cells classes apparently avoid direct cross-class homocellular coupling altogether even though they have opportunities via direct membrane touches, while transient OFF alpha ganglion cells and transient ON directionally selective (DS) ganglion cells are strongly coupled to distinct amacrine / axonal cell cohorts.A key feature of coupled ganglion cells is intercellular metabolite flux. Most GC::AC coupling involves GABAergic cells (γ+ amacrine cells), which results in significant GABA flux into ganglion cells. Surveying GABA coupling signatures in the ganglion cell layer across species suggests that the majority of vertebrate retinas engage in GC::AC coupling.Multi-hop synaptic queries of the entire RC1 connectome clearly profiles the coupled amacrine and axonal cells. Photic drive polarities and source bipolar cell class selec-tivities are tightly matched across coupled cells. OFF alpha ganglion cells are coupled to OFF γ+ amacrine cells and transient ON DS ganglion cells are coupled to ON γ+ amacrine cells including a large interstitial axonal cell (IAC). Synaptic tabulations show close matches between the classes of bipolar cells sampled by the coupled amacrine and ganglion cells. Further, both ON and OFF coupling ganglion networks show a common theme: synaptic asymmetry whereby the coupled γ+ neurons are also presynaptic to ganglion cell dendrites from different classes of ganglion cells outside the coupled set. In effect, these heterocellular coupling patterns enable an excited ganglion cell to directly inhibit nearby ganglion cells of different classes. Similarly, coupled γ+ amacrine cells engaged in feedback networks can leverage the additional gain of bipolar cell synapses in shaping the signaling of a spectrum of downstream targets based on their own selective coupling with ganglion cells.

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Reconvergence of a rod signal to an AII amacrine cell through divergence to a pair of rod bipolar cells in the mouse retina

Neuroscience Research ◽

10.1016/j.neures.2011.07.293 ◽

2011 ◽

Vol 71 ◽

pp. e69

Author(s):

Yoshihiko Tsukamoto ◽

Naoko Omi

Keyword(s):

Amacrine Cell ◽

Bipolar Cells ◽

Mouse Retina ◽

Rod Bipolar Cells ◽

Aii Amacrine

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Random spatial patterning of cone bipolar cell mosaics in the mouse retina

Visual Neuroscience ◽

10.1017/s0952523816000183 ◽

2017 ◽

Vol 34 ◽

Cited By ~ 2

Author(s):

PATRICK W. KEELEY ◽

JASON J. KIM ◽

SAMMY C.S. LEE ◽

SILKE HAVERKAMP ◽

BENJAMIN E. REESE

Keyword(s):

Bipolar Cell ◽

Amacrine Cells ◽

Cell Types ◽

Bipolar Cells ◽

Statistical Properties ◽

Horizontal Cells ◽

Mouse Retina ◽

Dendritic Arbors ◽

Cone Bipolar Cells ◽

Cholinergic Amacrine Cells

AbstractRetinal bipolar cells spread their dendritic arbors to tile the retinal surface, extending them to the tips of the dendritic fields of their homotypic neighbors, minimizing dendritic overlap. Such uniform nonredundant dendritic coverage of these populations would suggest a degree of spatial order in the properties of their somal distributions, yet few studies have examined the patterning in retinal bipolar cell mosaics. The present study examined the organization of two types of cone bipolar cells in the mouse retina, the Type 2 cells and the Type 4 cells, and compared their spatial statistical properties with those of the horizontal cells and the cholinergic amacrine cells, as well as to random simulations of cells matched in density and constrained by soma size. The Delauney tessellation of each field was computed, from which nearest neighbor distances and Voronoi domain areas were extracted, permitting a calculation of their respective regularity indexes (RIs). The spatial autocorrelation of the field was also computed, from which the effective radius and packing factor (PF) were determined. Both cone bipolar cell types were found to be less regular and less efficiently packed than either the horizontal cells or cholinergic amacrine cells. Furthermore, while the latter two cell types had RIs and PFs in excess of those for their matched random simulations, the two types of cone bipolar cells had spatial statistical properties comparable to random distributions. An analysis of single labeled cone bipolar cells revealed dendritic arbors frequently skewed to one side of the soma, as would be expected from a randomly distributed population of cells with dendrites that tile. Taken together, these results suggest that, unlike the horizontal cells or cholinergic amacrine cells which minimize proximity to one another, cone bipolar cell types are constrained only by their physical size.

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The somal patterning of the AII amacrine cell mosaic in the mouse retina is indistinguishable from random simulations matched for density and constrained by soma size

Visual Neuroscience ◽

10.1017/s0952523817000347 ◽

2018 ◽

Vol 35 ◽

Cited By ~ 1

Author(s):

PATRICK W. KEELEY ◽

BENJAMIN E. REESE

Keyword(s):

Amacrine Cell ◽

Amacrine Cells ◽

Bipolar Cells ◽

Horizontal Cells ◽

Mouse Retina ◽

Retinal Neurons ◽

Soma Size ◽

Aii Amacrine Cells ◽

Aii Amacrine ◽

Cholinergic Amacrine Cells

AbstractThe orderly spacing of retinal neurons is commonly regarded as a characteristic feature of retinal nerve cell populations. Exemplars of this property include the horizontal cells and the cholinergic amacrine cells, where individual cells minimize the proximity to like-type neighbors, yielding regularity in the patterning of their somata. Recently, two types of retinal bipolar cells in the mouse retina were shown to exhibit an order in their somal patterning no different from density-matched simulations constrained by soma size but being otherwise randomly distributed. The present study has now extended this finding to a type of retinal amacrine cell, the AII amacrine cell. Voronoi domain analysis revealed the patterning in the population of AII amacrine somata to be no different from density-matched and soma-size-constrained random simulations, while analysis of the density recovery profile showed AII amacrine cells to exhibit a minimal intercellular spacing identical to that for those random simulations: AII amacrine somata were positioned side-by-side as often as chance would predict. Regularity indexes and packing factors (PF) were far lower than those achieved by either the horizontal cells or cholinergic amacrine cells, with PFs also being comparable to those derived from the constrained random simulations. These results extend recent findings that call into question the widespread assumption that all types of retinal neurons are assembled as regular somal arrays, and have implications for the way in which AII amacrine cells must distribute their processes to ensure a uniform coverage of the retinal surface.

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Intrinsic bursting of AII amacrine cells underlies oscillations in the rd1 mouse retina

Journal of Neurophysiology ◽

10.1152/jn.00437.2014 ◽

2014 ◽

Vol 112 (6) ◽

pp. 1491-1504 ◽

Cited By ~ 49

Author(s):

Hannah Choi ◽

Lei Zhang ◽

Mark S. Cembrowski ◽

Carl F. Sabottke ◽

Alexander L. Markowitz ◽

...

Keyword(s):

Amacrine Cell ◽

Ganglion Cells ◽

Wild Type Mouse ◽

Amacrine Cells ◽

Bipolar Cells ◽

Membrane Properties ◽

Mouse Retina ◽

Intrinsic Membrane Properties ◽

Rd1 Mouse ◽

Aii Amacrine

In many forms of retinal degeneration, photoreceptors die but inner retinal circuits remain intact. In the rd1 mouse, an established model for blinding retinal diseases, spontaneous activity in the coupled network of AII amacrine and ON cone bipolar cells leads to rhythmic bursting of ganglion cells. Since such activity could impair retinal and/or cortical responses to restored photoreceptor function, understanding its nature is important for developing treatments of retinal pathologies. Here we analyzed a compartmental model of the wild-type mouse AII amacrine cell to predict that the cell's intrinsic membrane properties, specifically, interacting fast Na and slow, M-type K conductances, would allow its membrane potential to oscillate when light-evoked excitatory synaptic inputs were withdrawn following photoreceptor degeneration. We tested and confirmed this hypothesis experimentally by recording from AIIs in a slice preparation of rd1 retina. Additionally, recordings from ganglion cells in a whole mount preparation of rd1 retina demonstrated that activity in AIIs was propagated unchanged to elicit bursts of action potentials in ganglion cells. We conclude that oscillations are not an emergent property of a degenerated retinal network. Rather, they arise largely from the intrinsic properties of a single retinal interneuron, the AII amacrine cell.

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Modulation by Zn2+ of GABA responses in bipolar cells of the mouse retina

Visual Neuroscience ◽

10.1017/s0952523800172098 ◽

2000 ◽

Vol 17 (2) ◽

pp. 273-281 ◽

Cited By ~ 20

Author(s):

M. KANEDA ◽

B. ANDRÁSFALVY ◽

A. KANEKO

Keyword(s):

Axon Terminal ◽

Inhibitory Action ◽

Phosphinic Acid ◽

Amacrine Cells ◽

Bipolar Cells ◽

Mouse Retina ◽

Induced Responses ◽

Inhibitory Interaction ◽

Cell Recording ◽

Recording Conditions

The localization of endogenous Zn2+ in the mouse retina was examined histochemically and the inhibitory action of Zn2+ on GABA-induced responses was studied in bipolar cells isolated from the mouse retina. Accumulation of endogenous Zn2+ was detected in photoreceptors, bipolar, and/or amacrine cells by either the bromopyridylazo-diethylaminophenol method or the dithizone method. Under whole-cell recording conditions, GABA induced a Cl− current in isolated bipolar cells. The current consisted of two components. The first component was inhibited completely by application of 100 μM bicuculline, suggesting that this is a GABAA-receptor mediated current. The second component was inhibited completely by 100 μM 3-aminopropyl-(methyl)-phosphinic acid, suggesting that this is a GABAC-receptor mediated current. GABAC receptors were present at a higher density on the axon terminal than on dendrites. Zn2+ inhibited both GABAA and GABAC receptors. GABAC receptors were more susceptible to Zn2+; the IC50 for the GABAA receptor was 67.4 μM and that for the GABAC receptor was 1.9 μM. These results suggest that Zn2+ modulates the inhibitory interaction between amacrine and bipolar cells, particularly that mediated by the GABAC receptor.

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