Switching between transient and sustained signalling at the rod bipolar-AII amacrine cell synapse of the mouse retina

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

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

Dopaminergic amacrine cell number, plexus density, and dopamine content in the mouse retina: Strain differences and effects of Bax gene disruption

Experimental Eye Research ◽

10.1016/j.exer.2018.09.008 ◽

2018 ◽

Vol 177 ◽

pp. 208-212 ◽

Cited By ~ 4

Author(s):

Mathangi Sankaran ◽

Patrick W. Keeley ◽

Li He ◽

P. Michael Iuvone ◽

Benjamin E. Reese

Keyword(s):

Gene Disruption ◽

Amacrine Cell ◽

Strain Differences ◽

Cell Number ◽

Mouse Retina ◽

Dopamine Content ◽

Bax Gene

Download Full-text

Synaptic Transfer between Rod and Cone Pathways Mediated by AII Amacrine Cells in the Mouse Retina

Current Biology ◽

10.1016/j.cub.2018.06.063 ◽

2018 ◽

Vol 28 (17) ◽

pp. 2739-2751.e3 ◽

Cited By ~ 17

Author(s):

Cole W. Graydon ◽

Evan E. Lieberman ◽

Nao Rho ◽

Kevin L. Briggman ◽

Joshua H. Singer ◽

...

Keyword(s):

Amacrine Cells ◽

Mouse Retina ◽

Aii Amacrine Cells ◽

Aii Amacrine

Download Full-text

Ectopic localization of putative AII amacrine cells in the outer plexiform layer of the developing FVB/N mouse retina

Cell and Tissue Research ◽

10.1007/s00441-003-0844-8 ◽

2004 ◽

Vol 315 (3) ◽

pp. 407-412 ◽

Cited By ~ 7

Author(s):

Sung-Jin Park ◽

Eun-Jin Lim ◽

Su-Ja Oh ◽

Jin-Woong Chung ◽

Dennis W. Rickman ◽

...

Keyword(s):

Plexiform Layer ◽

Amacrine Cells ◽

Outer Plexiform Layer ◽

Mouse Retina ◽

Aii Amacrine Cells ◽

Aii Amacrine

Download Full-text

Simulation of the Aii amacrine cell of mammalian retina: Functional consequences of electrical coupling and regenerative membrane properties

Visual Neuroscience ◽

10.1017/s095252380000941x ◽

1995 ◽

Vol 12 (5) ◽

pp. 851-860 ◽

Cited By ~ 58

Author(s):

Robert G. Smith ◽

Noga Vardi

Keyword(s):

Gap Junctions ◽

Action Potentials ◽

Amacrine Cell ◽

Noise Removal ◽

Voltage Gated ◽

Mammalian Retina ◽

Coupling Conductance ◽

Slow Action Potentials ◽

Aii Amacrine

AbstractThe Aii amacrine cell of mammalian retina collects signals from several hundred rods and is hypothesized to transmit quantal “single-photon” signals at scotopic (starlight) intensities. One problem for this theory is that the quantal signal from one rod when summed with noise from neighboring rods would be lost if some mechanism did not exist for removing the noise. Several features of the Aii might together accomplish such a noise removal operation: The Aii is interconnected into a syncytial network by gap junctions, suggesting a noise-averaging function, and a quantal signal from one rod appears in five Aii cells due to anatomical divergence. Furthermore, the Aii contains voltage-gated Na+ and K+ channels and fires slow action potentials in vitro, suggesting that it could selectively amplify quantal photon signals embedded in uncorrelated noise. To test this hypothesis, we simulated a square array of AII somas (Rm = 25,000 Ohm-cm2) interconnected by gap junctions using a compartmental model. Simulated noisy inputs to the Aii produced noise (3.5 mV) uncorrelated between adjacent cells, and a gap junction conductance of 200 pS reduced the noise by a factor of 2.5, consistent with theory. Voltage-gated Na+ and K+ channels (Na+: 4 nS, K+: 0.4 nS) produced slow action potentials similar to those found in vitro in the presence of noise. For a narrow range of Na+ and coupling conductance, quantal photon events (-5–10 mV) were amplified nonlinearly by subthreshold regenerative events in the presence of noise. A lower coupling conductance produced spurious action potentials, and a greater conductance reduced amplification. Since the presence of noise in the weakly coupled circuit readily initiates action potentials that tend to spread throughout the AII network, we speculate that this tendency might be controlled in a negative feedback loop by up-modulating coupling or other synaptic conductances in response to spiking activity.

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