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

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.

Download Full-text

Dark-adapted response threshold of OFF ganglion cells is not set by OFF bipolar cells in the mouse retina

Journal of Neurophysiology ◽

10.1152/jn.01202.2011 ◽

2012 ◽

Vol 107 (10) ◽

pp. 2649-2659 ◽

Cited By ~ 27

Author(s):

A. Cyrus Arman ◽

Alapakkam P. Sampath

Keyword(s):

Ganglion Cells ◽

Amacrine Cells ◽

Bipolar Cells ◽

Response Threshold ◽

Mouse Retina ◽

Signal Flow ◽

Visual Threshold ◽

Aii Amacrine Cells ◽

Aii Amacrine ◽

Cone Bipolar Cells

The nervous system frequently integrates parallel streams of information to encode a broad range of stimulus strengths. In mammalian retina it is generally believed that signals generated by rod and cone photoreceptors converge onto cone bipolar cells prior to reaching the retinal output, the ganglion cells. Near absolute visual threshold a specialized mammalian retinal circuit, the rod bipolar pathway, pools signals from many rods and converges on depolarizing (AII) amacrine cells. However, whether subsequent signal flow to OFF ganglion cells requires OFF cone bipolar cells near visual threshold remains unclear. Glycinergic synapses between AII amacrine cells and OFF cone bipolar cells are believed to relay subsequently rod-driven signals to OFF ganglion cells. However, AII amacrine cells also make glycinergic synapses directly with OFF ganglion cells. To determine the route for signal flow near visual threshold, we measured the effect of the glycine receptor antagonist strychnine on response threshold in fully dark-adapted retinal cells. As shown previously, we found that response threshold for OFF ganglion cells was elevated by strychnine. Surprisingly, strychnine did not elevate response threshold in any subclass of OFF cone bipolar cell. Instead, in every OFF cone bipolar subclass strychnine suppressed tonic glycinergic inhibition without altering response threshold. Consistent with this lack of influence of strychnine, we found that the dominant input to OFF cone bipolar cells in darkness was excitatory and the response threshold of the excitatory input varied by subclass. Thus, in the dark-adapted mouse retina, the high absolute sensitivity of OFF ganglion cells cannot be explained by signal transmission through OFF cone bipolar cells.

Download Full-text

AMPA-selective glutamate receptor subunits GluR2 and GluR4 in the cat retina: An immunocytochemical study

Visual Neuroscience ◽

10.1017/s0952523899166100 ◽

1999 ◽

Vol 16 (6) ◽

pp. 1105-1114 ◽

Cited By ~ 52

Author(s):

PU QIN ◽

ROBERTA G. POURCHO

Keyword(s):

Ganglion Cells ◽

Plexiform Layer ◽

Amacrine Cells ◽

Cell Types ◽

Bipolar Cells ◽

Horizontal Cells ◽

Inner Plexiform Layer ◽

Cat Retina ◽

Aii Amacrine Cells ◽

Aii Amacrine

AMPA-selective glutamate receptors play a major role in glutamatergic neurotransmission in the retina and are expressed in a variety of neuronal subpopulations. In the present study, immunocytochemical techniques were used to visualize the distribution of GluR2 and GluR4 subunits in the cat retina. Results were compared with previous localizations of GluR1 and GluR2/3. Staining for GluR2 was limited to a small number of amacrine and ganglion cells whereas GluR4 staining was present in A-type horizontal cells, many amacrine cells including type AII amacrine cells, and the majority of the cells in the ganglion cell layer. Analysis of synaptic relationships in the outer plexiform layer showed the GluR4 subunit to be concentrated at the contacts of cone photoreceptors with A-horizontal cells. In the inner plexiform layer, both GluR2 and GluR4 were postsynaptic to cone bipolar cells at dyad contacts although GluR2 staining was limited to one of the postsynaptic elements whereas GluR4 immunoreactivity was often seen in both postsynaptic elements. Unlike GluR2, GluR4 was also postsynaptic to rod bipolar cells where it could be visualized in processes of AII amacrine cells. The data indicate that GluR3 and GluR4 subunits are colocalized in a number of cell types including A-type horizontal cells, AII amacrine cells, and alpha ganglion cells, but whether they are combined in the same multimeric receptors remains to be determined.

Download Full-text

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.

Download Full-text

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.

Download Full-text

Light-evoked current responses in rod bipolar cells, cone depolarizing bipolar cells and AII amacrine cells in dark-adapted mouse retina

The Journal of Physiology ◽

10.1113/jphysiol.2003.059543 ◽

2004 ◽

Vol 558 (3) ◽

pp. 897-912 ◽

Cited By ~ 45

Author(s):

Ji-Jie Pang ◽

Fan Gao ◽

Samuel M. Wu

Keyword(s):

Amacrine Cells ◽

Bipolar Cells ◽

Mouse Retina ◽

Rod Bipolar Cells ◽

Aii Amacrine Cells ◽

Aii Amacrine

Download Full-text

Meclofenamic Acid Blocks Electrical Synapses of Retinal AII Amacrine and on-Cone Bipolar Cells

Journal of Neurophysiology ◽

10.1152/jn.00112.2009 ◽

2009 ◽

Vol 101 (5) ◽

pp. 2339-2347 ◽

Cited By ~ 41

Author(s):

Margaret Lin Veruki ◽

Espen Hartveit

Keyword(s):

Amacrine Cells ◽

Bipolar Cells ◽

Electrical Synapse ◽

Dependent Manner ◽

Electrical Synapses ◽

Meclofenamic Acid ◽

Aii Amacrine Cells ◽

Rod Pathway ◽

Aii Amacrine ◽

Cone Bipolar Cells

Gap junction channels constitute specialized intercellular contacts that can serve as electrical synapses. In the rod pathway of the retina, electrical synapses between AII amacrine cells express connexin 36 (Cx36) and electrical synapses between AII amacrines and on-cone bipolar cells express Cx36 on the amacrine side and Cx36 or Cx45 on the bipolar side. For physiological investigations of the properties and functions of these electrical synapses, it is highly desirable to have access to potent pharmacological blockers with selective and reversible action. Here we use dual whole cell voltage-clamp recordings of pairs of AII amacrine cells and pairs of AII amacrine and on-cone bipolar cells in rat retinal slices to directly measure the junctional conductance ( Gj) between electrically coupled cells and to study the effect of the drug meclofenamic acid (MFA) on Gj. Consistent with previous tracer coupling studies, we found that MFA reversibly blocked the electrical synapse currents in a concentration-dependent manner, with complete block at 100 μM. Whereas MFA evoked a detectable decrease in Gj within minutes of application, the time to complete block of Gj was considerably longer, typically 20–40 min. After washout, Gj recovered to 20–90% of the control level, but the time to maximum recovery was typically >1 h. These results suggest that MFA can be a useful drug to investigate the physiological functions of electrical synapses in the rod pathway, but that the slow kinetics of block and reversal might compromise interpretation of the results and that explicit monitoring of Gj is desirable.

Download Full-text